Use of artificial intelligence in the design of small peptide antibiotics effective against a broad spectrum of highly antibiotic-resistant superbugs.

PubMed

Cherkasov, Artem; Hilpert, Kai; Jenssen, Håvard; Fjell, Christopher D; Waldbrook, Matt; Mullaly, Sarah C; Volkmer, Rudolf; Hancock, Robert E W

2009-01-16

Increased multiple antibiotic resistance in the face of declining antibiotic discovery is one of society's most pressing health issues. Antimicrobial peptides represent a promising new class of antibiotics. Here we ask whether it is possible to make small broad spectrum peptides employing minimal assumptions, by capitalizing on accumulating chemical biology information. Using peptide array technology, two large random 9-amino-acid peptide libraries were iteratively created using the amino acid composition of the most active peptides. The resultant data was used together with Artificial Neural Networks, a powerful machine learning technique, to create quantitative in silico models of antibiotic activity. On the basis of random testing, these models proved remarkably effective in predicting the activity of 100,000 virtual peptides. The best peptides, representing the top quartile of predicted activities, were effective against a broad array of multidrug-resistant "Superbugs" with activities that were equal to or better than four highly used conventional antibiotics, more effective than the most advanced clinical candidate antimicrobial peptide, and protective against Staphylococcus aureus infections in animal models.

Cloning and Expression of Synthetic Genes Encoding the Broad Antimicrobial Spectrum Bacteriocins SRCAM 602, OR-7, E-760, and L-1077, by Recombinant Pichia pastoris

PubMed Central

Jiménez, Juan J.; Gútiez, Loreto; Cintas, Luis M.; Herranz, Carmen; Hernández, Pablo E.

2015-01-01

We have evaluated the cloning and functional expression of previously described broad antimicrobial spectrum bacteriocins SRCAM 602, OR-7, E-760, and L-1077, by recombinant Pichia pastoris. Synthetic genes, matching the codon usage of P. pastoris, were designed from the known mature amino acid sequence of these bacteriocins and cloned into the protein expression vector pPICZαA. The recombinant derived plasmids were linearized and transformed into competent P. pastoris X-33, and the presence of integrated plasmids into the transformed cells was confirmed by PCR and sequencing of the inserts. The antimicrobial activity, expected in supernatants of the recombinant P. pastoris producers, was purified using a multistep chromatographic procedure including ammonium sulfate precipitation, desalting by gel filtration, cation exchange-, hydrophobic interaction-, and reverse phase-chromatography (RP-FPLC). However, a measurable antimicrobial activity was only detected after the hydrophobic interaction and RP-FPLC steps of the purified supernatants. MALDI-TOF MS analysis of the antimicrobial fractions eluted from RP-FPLC revealed the existence of peptide fragments of lower and higher molecular mass than expected. MALDI-TOF/TOF MS analysis of selected peptides from eluted RP-FPLC samples with antimicrobial activity indicated the presence of peptide fragments not related to the amino acid sequence of the cloned bacteriocins. PMID:25821820

Strategies for transformation of naturally-occurring amphibian antimicrobial peptides into therapeutically valuable anti-infective agents.

PubMed

Conlon, J Michael; Al-Ghaferi, Nadia; Abraham, Bency; Leprince, Jérôme

2007-08-01

The emergence of strains of pathogenic microorganisms with resistance to commonly used antibiotics has necessitated a search for novel types of antimicrobial agents. Many frog species produce amphipathic alpha-helical peptides with broad spectrum antimicrobial activity in the skin but their therapeutic potential is limited by varying degrees of cytolytic activity towards eukaryotic cells. Methods for development of such peptides into anti-infective drugs are illustrated by the example of temporin-1DRa (HFLGTLVNLAK KIL.NH(2)). Studies with model alpha-helical peptides have shown that increase in cationicity promotes antimicrobial activity whereas increases in hydrophobicity, helicity and amphipathicity promote hemolytic activity and loss of selectivity for microorganisms. Analogs of temporin-1DRa in which each amino acid is replaced by L-lysine and D-lysine were synthesized and their cytolytic activities tested against a range of microorganisms and human erythrocytes. Small changes in structure produced marked changes in conformation, as determined by retention time on reversed-phase HPLC, and in biological activity. However, peptides containing the substitutions (Val(7) -->L-Lys), (Thr(5)-->D-Lys) and (Asn(8)-->D-Lys) retained the high solubility and potent, broad spectrum antimicrobial activity of the naturally occurring peptide but were appreciably (up to 10-fold) less hemolytic. In contrast, analogs in which Leu(9) and Ile(13) were replaced by the more hydrophobic cyclohexylglycine residue showed slightly increased antimicrobial potencies (up to 2-fold) but a 4-fold increase in hemolytic activity. The data suggest a strategy of selective increases in cationicity concomitant with decreases in helicity and hydrophobicity in the transformation of naturally-occurring antimicrobial peptides into non-toxic therapeutic agents.

Brevibacillus laterosporus, a Pathogen of Invertebrates and a Broad-Spectrum Antimicrobial Species

PubMed Central

Ruiu, Luca

2013-01-01

Brevibacillus laterosporus, a bacterium characterized by the production of a unique canoe-shaped lamellar body attached to one side of the spore, is a natural inhabitant of water, soil and insects. Its biopesticidal potential has been reported against insects in different orders including Coleoptera, Lepidoptera, Diptera and against nematodes and mollusks. In addition to its pathogenicity against invertebrates, different B. laterosporus strains show a broad-spectrum antimicrobial activity including activity against phytopathogenic bacteria and fungi. A wide variety of molecules, including proteins and antibiotics, have been associated with the observed pathogenicity and mode of action. Before being considered as a biological control agent against plant pathogens, the antifungal and antibacterial properties of certain B. laterosporus strains have found medical interest, associated with the production of antibiotics with therapeutic effects. The recent whole genome sequencing of this species revealed its potential to produce polyketides, nonribosomal peptides, and toxins. Another field of growing interest is the use of this bacterium for bioremediation of contaminated sites by exploiting its biodegradation properties. The aim of the present review is to gather and discuss all recent findings on this emerging entomopathogen, giving a wider picture of its complex and broad-spectrum biocontrol activity. PMID:26462431

Endophytic Paraconiothyrium sp. from Zingiber officinale Rosc. Displays Broad-Spectrum Antimicrobial Activity by Production of Danthron.

PubMed

Anisha, C; Sachidanandan, P; Radhakrishnan, E K

2018-03-01

The bioactivity spectrum of fungal endophytes isolated from Zingiber officinale was analyzed against clinical pathogens and against the phytopathogen Pythium myriotylum, which causes Pythium rot in ginger. One of the isolates GFM13 showed broad bioactivity against various pathogens tested including P. myriotylum. The spore suspension as well as the culture filtrate of the endophytic fungal isolate was found to effectively protect ginger rhizomes from Pythium rot. By molecular identification, the fungal endophyte was identified as Paraconiothyrium sp. The bioactive compound produced by the isolate was separated by bioactivity-guided fractionation and was identified by GC-MS as danthron, an anthraquinone derivative. PCR amplification showed the presence of non-reducing polyketide synthase gene (NR-PKS) in the endophyte GFM13, which is reported to be responsible for the synthesis of anthraquinones in fungi. This is the first report of danthron being produced as the biologically active component of Paraconiothyrium sp. Danthron is reported to have wide pharmaceutical and agronomic applications which include its use as a fungicide in agriculture. The broad-spectrum antimicrobial activity of danthron and the endophytic origin of Paraconiothyrium sp. offer immense applications of the study.

Black cobra (Naja naja karachiensis) lysates exhibit broad-spectrum antimicrobial activities

PubMed Central

Sagheer, Mehwish; Siddiqui, Ruqaiyyah; Iqbal, Junaid; Khan, Naveed Ahmed

2014-01-01

It is hypothesized that animals living in polluted environments possess antimicrobials to counter pathogenic microbes. The fact that snakes feed on germ-infested rodents suggests that they encounter pathogenic microbes and likely possess antimicrobials. The venom is used only to paralyze the rodent, but the ability of snakes to counter potential infections in the gut due to disease-ridden rodents requires robust action of the immune system against a broad range of pathogens. To test this hypothesis, crude lysates of different organs of Naja naja karachiensis (black cobra) were tested for antimicrobial properties. The antimicrobial activities of extracts were tested against selected bacterial pathogens (neuropathogenic Escherichia coli K1, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, and Streptococcus pneumonia), protist (Acanthamoeba castellanii), and filamentous fungus (Fusarium solani). The findings revealed that plasma and various organ extracts of N. n. karachiensis exhibited antimicrobial activity against E. coli K1, MRSA, P. aeruginosa, S. pneumoniae, A. castellanii, and F. solani in a concentration-dependent manner. The results of this study are promising for the development of new antimicrobials. PMID:24625321

Antimicrobial and anticancer potential of low molecular weight polypeptides extracted and characterized from leaves of Azadirachta indica.

PubMed

Al Saiqali, Mohammed; Tangutur, Anjana Devi; Banoth, Chandrasekhar; Bhukya, Bhima

2018-07-15

Low molecular weight antimicrobial polypeptides were extracted and purified from the young fresh leaves of Azadirachta indica (neem). The total protein extracted was precipitated with 15% TCA-Acetone. The total purified proteins yielded from the two extraction methods were 122.33±2.21 and 115.09±1.88mg/g of the total fresh weight. The SDS-PAGE analysis identified the presence of eight low molecular weight polypeptide bands. The antimicrobial activity of the resolved bands was detected by Polyacrylamide gel-Agar overlay diffusion assay (PAG-ADA). Their broad-spectrum bactericidal activity was confirmed using the same technique and found three low molecular weight bands from 11 to 14kDa collectively exhibiting superior bactericidal activities against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermis, Enterococcus faecalis, Pseudomonas aeruginosa and fungicidal activity against Candida tropicalis. The FTIR spectrum of the protein bands depicted the presence of hydroxyl and carbonyl groups in the protein bands. These polypeptides were characterized by MALDI-TOF/TOF analysis. Further, the purified protein extract was found to be active against HELA, BT-549 and Neuro-2a cell lines with IC 50 value of 74.03±2.31, 64.82±1.64, 238.32±2.12 and 109.94±2.96, 59.61±0.75 for 24h and 48h, respectively. The results of present study indicate that these polypeptides exhibit broad spectrum antimicrobial and anticancer activity and can therefore be explored for their therapeutic potential. Copyright © 2018 Elsevier B.V. All rights reserved.

Antimicrobial activity of tiger's betel (Piper porphyrophyllum N.E. Br., Piperaceae).

PubMed

Wiart, C; Hannah, N A; Yassim, M; Hamimah, H; Sulaiman, M

2004-09-01

The ethanol extract of leaves of Piper porphyrophyllum N.E. Br. showed a broad spectrum of antibacterial activity. The activity was increased on fractionation (hexane, dichloromethane and aqueous), particularly in the aqueous fraction. No activity was shown against tested Candida albicans. Copyright (c) 2004 John Wiley & Sons, Ltd.

Insights into Antimicrobial Peptides from Spiders and Scorpions

PubMed Central

Wang, Xiuqing; Wang, Guangshun

2015-01-01

The venoms of spiders and scorpions contain a variety of chemical compounds. Antimicrobial peptides (AMPs) from these organisms were first discovered in the 1990s. As of May 2015, there were 42 spider’s and 63 scorpion’s AMPs in the Antimicrobial Peptide Database (http://aps.unmc.edu/AP). These peptides have demonstrated broad or narrow-spectrum activities against bacteria, fungi, viruses, and parasites. In addition, they can be toxic to cancer cells, insects and erythrocytes. To provide insight into such an activity spectrum, this article discusses the discovery, classification, structure and activity relationships, bioinformatics analysis, and potential applications of spider and scorpion AMPs. Our analysis reveals that, in the case of linear peptides, spiders use both glycine-rich and helical peptide models for defense, whereas scorpions use two distinct helical peptide models with different amino acid compositions to exert the observed antimicrobial activities and hemolytic toxicity. Our structural bioinformatics study improves the knowledge in the field and can be used to design more selective peptides to combat tumors, parasites, and viruses. PMID:27165405

The in vitro Antimicrobial Activity and Chemometric Modelling of 59 Commercial Essential Oils against Pathogens of Dermatological Relevance.

PubMed

Orchard, Ané; Sandasi, Maxleene; Kamatou, Guy; Viljoen, Alvaro; van Vuuren, Sandy

2017-01-01

This study reports on the inhibitory concentration of 59 commercial essential oils recommended for dermatological conditions, and identifies putative compounds responsible for antimicrobial activity. Essential oils were investigated for antimicrobial activity using minimum inhibitory concentration assays. Ten essential oils were identified as having superior antimicrobial activity. The essential oil compositions were determined using gas chromatography coupled to mass spectrometry and the data analysed with the antimicrobial activity using multivariate tools. Orthogonal projections to latent structures models were created for seven of the pathogens. Eugenol was identified as the main biomarker responsible for antimicrobial activity in the majority of the essential oils. The essential oils mostly displayed noteworthy antimicrobial activity, with five oils displaying broad-spectrum activity against the 13 tested micro-organisms. The antimicrobial efficacies of the essential oils highlight their potential in treating dermatological infections and through chemometric modelling, bioactive volatiles have been identified. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Purification and characteristics of a novel bacteriocin produced by Enterococcus faecalis L11 isolated from Chinese traditional fermented cucumber.

PubMed

Gao, Yurong; Li, Benling; Li, Dapeng; Zhang, Liyuan

2016-05-01

To purify and characterize a novel bacteriocin with broad inhibitory spectrum produced by an isolate of Enterococcus faecalis from Chinese fermented cucumber. E. faecalis L11 produced a bacteriocin with antimicrobial activity against both Escherichia coli and Staphylococcus aureus. The amino acid sequence of the purified bacteriocin, enterocin L11, was assayed by Edman degradation method. It differs from other class II bacteriocins and exhibited a broad antimicrobial activity against not only Gram-positive bacteria, including Bacillus subtilis, S. aureus, Listeria monocytogenes, Sarcina flava, Lactobacillus acidophilus, L. plantarum, L. delbrueckii subsp. delbrueckii, L. delbrueckii subsp. bulgaricus and Streptococcus thermophilus, but also some Gram-negative bacteria including Salmonella typhimurium, E. coli and Shigella flexneri. Enterocin L11 retained 91 % of its activity after holding at 121 °C for 30 min. It was also resistant to acids and alkalis. Enterocin L11 is a novel broad-spectrum Class II bacteriocin produced by E. faecalis L11, and may have potential as a food biopreservative.

Shell thickness-dependent antibacterial activity and biocompatibility of gold@silver core–shell nanoparticles

USDA-ARS?s Scientific Manuscript database

Antimicrobial activity of silver is highly effective and broad-spectrum; however, poor long-term antibacterial efficiency and cytotoxicity toward mammalian cells have restricted their applications. Here, we fabricated Au@Ag NPs with tailored shell thickness, and investigated their antibacterial acti...

Recent updates of marine antimicrobial peptides.

PubMed

Semreen, Mohammad H; El-Gamal, Mohammed I; Abdin, Shifaa; Alkhazraji, Hajar; Kamal, Leena; Hammad, Saba; El-Awady, Faten; Waleed, Dima; Kourbaj, Layal

2018-03-01

Antimicrobial peptides are group of proteins showing broad-spectrum antimicrobial activity that have been known to be powerful agents against a variety of pathogens. This class of compounds contributed to solving the microbial resistance dilemma that limited the use of many potent antimicrobial agents. The marine environment is known to be one of the richest sources for antimicrobial peptides, yet this environment is not fully explored. Hence, the scientific research attention should be directed toward the marine ecosystem as enormous amount of useful discoveries could be brought to the forefront. In the current article, the marine antimicrobial peptides reported from mid 2012 to 2017 have been reviewed.

Reduction of Broad-Spectrum Antimicrobial Use in a Tertiary Children's Hospital Post Antimicrobial Stewardship Program Guideline Implementation.

PubMed

Lee, Kelley R; Bagga, Bindiya; Arnold, Sandra R

2016-03-01

The core strategies recommended for antimicrobial stewardship programs, formulary restriction with preauthorization and prospective audit and feedback, can be difficult to implement with limited resources; therefore, we took an approach of guideline development and education with the goal of reducing overall antibiotic use and unwarranted use of broad-spectrum antimicrobials. Retrospective chart review before and after intervention. Le Bonheur Children's Hospital pediatric, neonatal, and cardiac ICUs. All patients in our pediatric, neonatal, and cardiac ICUs within the time frame of the study. Baseline review in our ICUs revealed excessive use of broad-spectrum antibiotics and inconsistency in managing common pediatric infections. Guidelines were developed and implemented using cycles of education, retrospective review, and feedback. Purchasing and antibiotic use data were obtained to assess changes before and after guideline implementation. Unit-specific days of therapy were measured using periodic chart audit. Segmented regression analysis was used to assess changes in purchasing and broad-spectrum antibiotic days of therapy. The change in median monthly purchases was assessed using 2-tail Student t test. Hospital-wide targeted broad-spectrum antibiotic days of therapy/1,000 patient-days during the preimplementation year averaged 105 per month and decreased 33% to 70 per month during the postimplementation year. The overall antibiotic days of therapy decreased 41%, 21%, and 18%, and targeted broad-spectrum antibiotic days of therapy decreased by 99%, 75%, and 61% in the cardiac, pediatric, and neonatal ICUs, respectively, after guideline implementation. Yearly purchases of our most common broad-spectrum antibiotics decreased 62% from $230,059 to $86,887 after guideline implementation. Median monthly purchases of these drugs before implementation were $19,389 and $11,043 after implementation (p < 0.001). Guideline implementation was successful in reducing targeted broad-spectrum antibiotic use and acquisition cost. Programs with very limited resources may find similar implementation of guidelines effective to provide initial success, so that putting into practice one of the more resource intensive core strategies, such as prospective audit and feedback, may be feasible.

Polyketide family of novel antibacterial 7-O-methyl-5'-hydroxy-3'-heptenoate-macrolactin from seaweed-associated Bacillus subtilis MTCC 10403.

PubMed

Chakraborty, Kajal; Thilakan, Bini; Raola, Vamshi Krishna

2014-12-17

Seaweed-associated heterotrophic bacterial communities were screened to isolate potentially useful antimicrobial strains, which were characterized by phylogenetic analysis. The bacteria were screened for the presence of metabolite genes involved in natural product biosynthetic pathway, and the structural properties of secondary metabolites were correlated with the genes. Bioactivity-guided isolation of polyene antibiotic 7-O-methyl-5'-hydroxy-3'-heptenoate-macrolactin from Bacillus subtilis MTCC10403 associated with seaweed Anthophycus longifolius using mass spectrometry and extensive 2D-NMR studies was carried out. The newly isolated macrolactin compound is a bactericidal antibiotic with broad spectrum activity against human opportunistic clinical pathogens. The biosynthetic pathway of 7-O-methyl-5'-hydroxy-3'-heptenoate-macrolactin by means of a stepwise, decarboxylative condensation pathway established the PKS-assisted biosynthesis of the parent macrolactin and the side-chain 5-hydroxyhept-3-enoate moiety attached to the macrolactin ring system at C-7. Antimicrobial activity analysis combined with the results of amplifying genes encoding for polyketide synthetase and nonribosomal peptide synthetase showed that seaweed-associated bacteria had broad-spectrum antimicrobial activity. The present work may have an impact on the exploitation of macrolactins for pharmaceutical and biotechnological applications.

Defining Antimicrobial Textile Requirements for Military Applications - A Gap Analysis

DTIC Science & Technology

2016-05-09

biocide that has broad spectrum antibacterial , antiviral, and antifungal activity . Copper behaves similarly to silver by binding and inactivating...urogenital health conditions in active duty Soldiers from 2002-2011...personnel in order to generate and update requirements and standards for incorporating anti-odor, antibacterial , and antifungal properties into CIE

Antagonistic activity of Bacillus subtilis SB1 and its biocontrol effect on tomato bacterial wilt

USDA-ARS?s Scientific Manuscript database

A potential biocontrol agent of bacterial wilt, Bacillus subtilis SB1, isolated from tomato roots, showed a broad-spectrum of antimicrobial activity in in vitro experiments. It inhibited the growth of many plant pathogens, including Ralstonia solanacearum, Xanthomonas oryzae pv. oryzae, Fusarium ox...

Molecular and chemical dialogues in bacteria-protozoa interactions

USDA-ARS?s Scientific Manuscript database

Soil-dwelling Pseudomonas fluorescens produce lipopeptide surfactants (LPs) with broad-spectrum antimicrobial activities. Recent studies suggested that LPs provide protection to P. fluorescens strain SS101 against grazing by the predatory protozoa Naegleria americana, both in vitro and in rhizospher...

Novel Group of Leaderless Multipeptide Bacteriocins from Gram-Positive Bacteria.

PubMed

Ovchinnikov, Kirill V; Chi, Hai; Mehmeti, Ibrahim; Holo, Helge; Nes, Ingolf F; Diep, Dzung B

2016-09-01

From raw milk we found 10 Lactococcus garvieae isolates that produce a new broad-spectrum bacteriocin. Though the isolates were obtained from different farms, they turned out to possess identical inhibitory spectra, fermentation profiles of sugars, and repetitive sequence-based PCR (rep-PCR) DNA patterns, indicating that they produce the same bacteriocin. One of the isolates (L. garvieae KS1546) was chosen for further assessment. Purification and peptide sequencing combined with genome sequencing revealed that the antimicrobial activity was due to a bacteriocin unit composed of three similar peptides of 32 to 34 amino acids. The three peptides are produced without leader sequences, and their genes are located next to each other in an operon-like structure, adjacent to the genes normally involved in bacteriocin transport (ABC transporter) and self-immunity. The bacteriocin, termed garvicin KS (GarKS), showed sequence homology to four multipeptide bacteriocins in databases: the known staphylococcal aureocin A70, consisting of four peptides, and three unannotated putative multipeptide bacteriocins produced by Bacillus cereus All these multipeptide bacteriocin loci show conserved genetic organization, including being located adjacent to conserved genetic determinants (Cro/cI and integrase) which are normally associated with mobile genetic elements or genome rearrangements. The antimicrobial activity of all multipeptide bacteriocins was confirmed with synthetic peptides, and all were shown to have broad antimicrobial spectra, with GarKS being the most active of them. The inhibitory spectrum of GarKS includes important pathogens belonging to the genera Staphylococcus, Bacillus, Listeria, and Enterococcus Bacterial resistance to antibiotics is a very serious global problem. There are no new antibiotics with novel antimicrobial mechanisms in clinical trials. Bacteriocins use antimicrobial mechanisms different from those of antibiotics and can kill antibiotic-resistant bacteria, but the number of bacteriocins with very broad antimicrobial spectra is very small. In this study, we have found and purified a novel three-peptide bacteriocin, garvicin KS. By homology search, we were able to find one known and three novel sequence-related bacteriocins consisting of 3 or 4 peptides. None of the peptides has modified amino acids in its sequence. Thus, the activity of all bacteriocins was confirmed with chemically synthesized peptides. All of them, especially garvicin KS, have very broad antibacterial spectra, thus representing a great potential in antimicrobial applications in the food industry and medicine. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Novel Group of Leaderless Multipeptide Bacteriocins from Gram-Positive Bacteria

PubMed Central

Chi, Hai; Mehmeti, Ibrahim; Holo, Helge; Nes, Ingolf F.

2016-01-01

ABSTRACT From raw milk we found 10 Lactococcus garvieae isolates that produce a new broad-spectrum bacteriocin. Though the isolates were obtained from different farms, they turned out to possess identical inhibitory spectra, fermentation profiles of sugars, and repetitive sequence-based PCR (rep-PCR) DNA patterns, indicating that they produce the same bacteriocin. One of the isolates (L. garvieae KS1546) was chosen for further assessment. Purification and peptide sequencing combined with genome sequencing revealed that the antimicrobial activity was due to a bacteriocin unit composed of three similar peptides of 32 to 34 amino acids. The three peptides are produced without leader sequences, and their genes are located next to each other in an operon-like structure, adjacent to the genes normally involved in bacteriocin transport (ABC transporter) and self-immunity. The bacteriocin, termed garvicin KS (GarKS), showed sequence homology to four multipeptide bacteriocins in databases: the known staphylococcal aureocin A70, consisting of four peptides, and three unannotated putative multipeptide bacteriocins produced by Bacillus cereus. All these multipeptide bacteriocin loci show conserved genetic organization, including being located adjacent to conserved genetic determinants (Cro/cI and integrase) which are normally associated with mobile genetic elements or genome rearrangements. The antimicrobial activity of all multipeptide bacteriocins was confirmed with synthetic peptides, and all were shown to have broad antimicrobial spectra, with GarKS being the most active of them. The inhibitory spectrum of GarKS includes important pathogens belonging to the genera Staphylococcus, Bacillus, Listeria, and Enterococcus. IMPORTANCE Bacterial resistance to antibiotics is a very serious global problem. There are no new antibiotics with novel antimicrobial mechanisms in clinical trials. Bacteriocins use antimicrobial mechanisms different from those of antibiotics and can kill antibiotic-resistant bacteria, but the number of bacteriocins with very broad antimicrobial spectra is very small. In this study, we have found and purified a novel three-peptide bacteriocin, garvicin KS. By homology search, we were able to find one known and three novel sequence-related bacteriocins consisting of 3 or 4 peptides. None of the peptides has modified amino acids in its sequence. Thus, the activity of all bacteriocins was confirmed with chemically synthesized peptides. All of them, especially garvicin KS, have very broad antibacterial spectra, thus representing a great potential in antimicrobial applications in the food industry and medicine. PMID:27316965

Synthetic membrane-targeted antibiotics.

PubMed

Vooturi, S K; Firestine, S M

2010-01-01

Antimicrobial resistance continues to evolve and presents serious challenges in the therapy of both nosocomial and community-acquired infections. The rise of resistant strains like methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus (VRSA) and vancomycin-resistant enterococci (VRE) suggests that antimicrobial resistance is an inevitable evolutionary response to antimicrobial use. This highlights the tremendous need for antibiotics against new bacterial targets. Agents that target the integrity of bacterial membrane are relatively novel in the clinical armamentarium. Daptomycin, a lipopeptide is a classical example of membrane-bound antibiotic. Nature has also utilized this tactic. Antimicrobial peptides (AMPs), which are found in all kingdoms, function primarily by permeabilizing the bacterial membrane. AMPs have several advantages over existing antibiotics including a broad spectrum of activity, rapid bactericidal activity, no cross-resistance with the existing antibiotics and a low probability for developing resistance. Currently, a small number of peptides have been developed for clinical use but therapeutic applications are limited because of poor bioavailability and high manufacturing cost. However, their broad specificity, potent activity and lower probability for resistance have spurred the search for synthetic mimetics of antimicrobial peptides as membrane-active antibiotics. In this review, we will discuss the different classes of synthetic membrane-bound antibiotics published since 2004.

Antimicrobial properties of Honduran medicinal plants.

PubMed

Lentz, D L; Clark, A M; Hufford, C D; Meurer-Grimes, B; Passreiter, C M; Cordero, J; Ibrahimi, O; Okunade, A L

1998-12-01

Ninety-two plants used in the traditional pharmacopoeia of the Pech and neighboring Mestizo peoples of central Honduras are reported. The results of in vitro antimicrobial screens showed that 19 of the extracts from medicinal plants revealed signs of antifungal activity while 22 demonstrated a measurable inhibitory effect on one or more bacterial cultures. Bioassay-guided fractionation of extracts from Mikania micrantha, Neurolaena lobata and Piper aduncum produced weak to moderately active isolates. The broad spectrum of activity of the extracts helps to explain the widespread use of these plants for wound healing and other applications.

Cationic Biomimetic Particles of Polystyrene/Cationic Bilayer/Gramicidin for Optimal Bactericidal Activity.

PubMed

Xavier, Gabriel R S; Carmona-Ribeiro, Ana M

2017-12-02

Nanostructured particles of polystyrene sulfate (PSS) covered by a cationic lipid bilayer of dioctadecyldimethylammonium bromide (DODAB) incorporated gramicidin D (Gr) yielding optimal and broadened bactericidal activity against both Escherichia coli and Staphylococcus aureus . The adsorption of DODAB/Gr bilayer onto PSS nanoparticles (NPs) increased the zeta-average diameter by 8-10 nm, changed the zeta-potential of the NPs from negative to positive, and yielded a narrow size distributions for the PSS/DODAB/Gr NPs, which displayed broad and maximal microbicidal activity at very small concentrations of the antimicrobials, namely, 0.057 and 0.0057 mM DODAB and Gr, respectively. The results emphasized the advantages of highly-organized, nanostructured, and cationic particles to achieve hybrid combinations of antimicrobials with broad spectrum activity at considerably reduced DODAB and Gr concentrations.

Archetypal tryptophan-rich antimicrobial peptides: properties and applications.

PubMed

Shagaghi, Nadin; Palombo, Enzo A; Clayton, Andrew H A; Bhave, Mrinal

2016-02-01

Drug-resistant microorganisms ('superbugs') present a serious challenge to the success of antimicrobial treatments. Subsequently, there is a crucial need for novel bio-control agents. Many antimicrobial peptides (AMPs) show a broad-spectrum activity against bacteria, fungi or viruses and are strong candidates to complement or substitute current antimicrobial agents. Some AMPs are also effective against protozoa or cancer cells. The tryptophan (Trp)-rich peptides (TRPs) are a subset of AMPs that display potent antimicrobial activity, credited to the unique biochemical properties of tryptophan that allow it to insert into biological membranes. Further, many Trp-rich AMPs cross bacterial membranes without compromising their integrity and act intracellularly, suggesting interactions with nucleic acids and enzymes. In this work, we overview some archetypal TRPs derived from natural sources, i.e., indolicidin, tritrpticin and lactoferricin, summarising their biochemical properties, structures, antimicrobial activities, mechanistic studies and potential applications.

Chitosan-thioglycolic acid as a versatile antimicrobial agent.

PubMed

Geisberger, Georg; Gyenge, Emina Besic; Hinger, Doris; Käch, Andres; Maake, Caroline; Patzke, Greta R

2013-04-08

As functionalized chitosans hold great potential for the development of effective and broad-spectrum antibiotics, representative chitosan derivatives were tested for antimicrobial activity in neutral media: trimethyl chitosan (TMC), carboxy-methyl chitosan (CMC), and chitosan-thioglycolic acid (TGA; medium molecular weight: MMW-TGA; low molecular weight: LMW-TGA). Colony forming assays indicated that LMW-TGA displayed superior antimicrobial activity over the other derivatives tested: a 30 min incubation killed 100% Streptococcus sobrinus (Gram-positive bacteria) and reduced colony counts by 99.99% in Neisseria subflava (Gram-negative bacteria) and 99.97% in Candida albicans (fungi). To elucidate LMW-TGA effects at the cellular level, microscopic studies were performed. Use of fluorescein isothiocyanate (FITC)-labeled chitosan derivates in confocal microscopy showed that LMW-TGA attaches to microbial cell walls, while transmission electron microscopy indicated that this derivative severely affects cell wall integrity and intracellular ultrastructure in all species tested. We therefore propose LMW-TGA as a promising and effective broad-band antimicrobial compound.

Identification and Structural Characterization of Naturally-Occurring Broad-Spectrum Cyclic Antibiotics Isolated from Paenibacillus

NASA Astrophysics Data System (ADS)

Knolhoff, Ann M.; Zheng, Jie; McFarland, Melinda A.; Luo, Yan; Callahan, John H.; Brown, Eric W.; Croley, Timothy R.

2015-08-01

The rise of antimicrobial resistance necessitates the discovery and/or production of novel antibiotics. Isolated strains of Paenibacillus alvei were previously shown to exhibit antimicrobial activity against a number of pathogens, such as E. coli, Salmonella, and methicillin-resistant Staphylococcus aureus (MRSA). The responsible antimicrobial compounds were isolated from these Paenibacillus strains and a combination of low and high resolution mass spectrometry with multiple-stage tandem mass spectrometry was used for identification. A group of closely related cyclic lipopeptides was identified, differing primarily by fatty acid chain length and one of two possible amino acid substitutions. Variation in the fatty acid length resulted in mass differences of 14 Da and yielded groups of related MSn spectra. Despite the inherent complexity of MS/MS spectra of cyclic compounds, straightforward analysis of these spectra was accomplished by determining differences in complementary product ion series between compounds that differ in molecular weight by 14 Da. The primary peptide sequence assignment was confirmed through genome mining; the combination of these analytical tools represents a workflow that can be used for the identification of complex antibiotics. The compounds also share amino acid sequence similarity to a previously identified broad-spectrum antibiotic isolated from Paenibacillus. The presence of such a wide distribution of related compounds produced by the same organism represents a novel class of broad-spectrum antibiotic compounds.

Impact of computerized pre-authorization of broad spectrum antibiotics in Pseudomonas aeruginosa at a children's hospital in Japan.

PubMed

Horikoshi, Yuho; Higuchi, Hiroshi; Suwa, Junichi; Isogai, Mihoko; Shoji, Takayo; Ito, Kenta

2016-08-01

The spread of antimicrobial-resistant organisms is a global concern. To stem this tide, an antimicrobial stewardship program at hospitals is essential to optimize the prescription of broad spectrum antibiotics. In this study we examined the impact of computerized pre-authorization for broad spectrum antibiotics for Pseudomonas aeruginosa at a children's hospital. An antimicrobial stewardship program at Tokyo Metropolitan Children's Medical Center was assessed between March 2010 and March 2015. A paper-based post-prescription audit was switched to computerized pre-authorization for broad antipseudomonal agents in October 2011. The prescriber was required to obtain approval from physicians in the pediatric infectious diseases division before prescribing restricted antimicrobial agents. Approved prescriptions were processed and logged electronically. We evaluated days of therapy per 1000 patient-days, the cost of antibiotics, and the susceptibility of P. aeruginosa to piperacillin, ceftazidime, cefepime, piperacillin/tazobactam, carbapenems, and ciprofloxacin. Also, the average length of admission and infection-related mortality at 30 days were compared pre- and post-intervention. Administration of carbapenems, piperacillin/tazobactam, and ceftazidime decreased significantly after the introduction of computerized pre-authorization. Antibiotic costs were reduced by JPY2.86 million (USD 26,000) annually. None of the antipseudomonal agents showed decreased sensitivity. The average length of admission was shorter in post-intervention. Infection-related mortality at 30 days showed no difference between the pre- and post-intervention periods. An antimicrobial stewardship program using computerized pre-authorization decreased the use and cost of broad spectrum antibiotics without significant difference in infection-related mortality at 30 days, although our study did not improve susceptibilities of P. aeruginosa. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Screening of antimicrobial activity of macroalgae extracts from the Moroccan Atlantic coast.

PubMed

El Wahidi, M; El Amraoui, B; El Amraoui, M; Bamhaoud, T

2015-05-01

The aim of this work is the screening of the antimicrobial activity of seaweed extracts against pathogenic bacteria and yeasts. The antimicrobial activity of the dichloromethane and ethanol extracts of ten marine macroalgae collected from the Moroccan's Atlantic coast (El-Jadida) was tested against two Gram+ (Bacillus subtilis and Staphylococcus aureus) and two Gram- (Escherichia coli and Pseudomonas aeruginosa) human pathogenic bacteria, and against two pathogenic yeasts (Candida albicans and Cryptococcus neoformans) using the agar disk-diffusion method. Seven algae (70%) of ten seaweeds are active against at least one pathogenic microorganisms studied. Five (50%) are active against the two studied yeast with an inhibition diameter greater than 15 mm for Cystoseira brachycarpa. Six (60%) seaweeds are active against at least one studied bacteria with five (50%) algae exhibiting antibacterial inhibition diameter greater than 15 mm. Cystoseira brachycarpa, Cystoseira compressa, Fucus vesiculosus, and Gelidium sesquipedale have a better antimicrobial activity with a broad spectrum antimicrobial and are a potential source of antimicrobial compounds and can be subject of isolation of the natural antimicrobials. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Characterization of antimicrobial lipopeptides produced by Bacillus sp. LM7 isolated from chungkookjang, a Korean traditional fermented soybean food.

PubMed

Lee, Mi-Hwa; Lee, Jiyeon; Nam, Young-Do; Lee, Jong Suk; Seo, Myung-Ji; Yi, Sung-Hun

2016-03-16

A wild-type microorganism exhibiting antimicrobial activities was isolated from the Korean traditional fermented soybean food Chungkookjang and identified as Bacillus sp. LM7. During its stationary growth phase, the microorganism secreted an antimicrobial substance, which we partially purified using a simple two-step procedure involving ammonium sulfate precipitation and heat treatment. The partially purified antimicrobial substance, Anti-LM7, was stable over a broad pH range (4.0-9.0) and at temperatures up to 80 °C for 30 min, and was resistant to most proteolytic enzymes and maintained its activity in 30% (v/v) organic solvents. Anti-LM7 inhibited the growth of a broad range of Gram-positive bacteria, including Bacillus cereus and Listeria monocytogenes, but it did not inhibit lactic acid bacteria such as Lactobacillus plantarum and Lactococcus lactis subsp. Lactis. Moreover, unlike commercially available nisin and polymyxin B, Anti-LM7 inhibited certain fungal strains. Lastly, liquid chromatography-mass spectrometry analysis of Anti-LM7 revealed that it contained eight lipopeptides belonging to two families: four bacillomycin D and four surfactin analogs. These Bacillus sp. LM7-produced heterogeneous lipopeptides exhibiting extremely high stability and a broad antimicrobial spectrum are likely to be closely related to the antimicrobial activity of Chungkookjang, and their identification presents an opportunity for application of the peptides in environmental bioremediation, pharmaceutical, cosmetic, and food industries. Copyright © 2015 Elsevier B.V. All rights reserved.

Fatty acid conjugation enhances the activities of antimicrobial peptides.

PubMed

Li, Zhining; Yuan, Penghui; Xing, Meng; He, Zhumei; Dong, Chuanfu; Cao, Yongchang; Liu, Qiuyun

2013-04-01

Antimicrobial peptides are small molecules that play a crucial role in innate immunity in multi-cellular organisms, and usually expressed and secreted constantly at basal levels to prevent infection, but local production can be augmented upon an infection. The clock is ticking as rising antibiotic abuse has led to the emergence of many drug resistance bacteria. Due to their broad spectrum antibiotic and antifungal activities as well as anti-viral and anti-tumor activities, efforts are being made to develop antimicrobial peptides into future microbial agents. This article describes some of the recent patents on antimicrobial peptides with fatty acid conjugation. Potency and selectivity of antimicrobial peptide can be modulated with fatty acid tails of variable length. Interaction between membranes and antimicrobial peptides was affected by fatty acid conjugation. At concentrations above the critical miscelle concentration (CMC), propensity of solution selfassembly hampered binding of the peptide to cell membranes. Overall, fatty acid conjugation has enhanced the activities of antimicrobial peptides, and occasionally it rendered inactive antimicrobial peptides to be bioactive. Antimicrobial peptides can not only be used as medicine but also as food additives.

Broad spectrum antimicrobial activity of melimine covalently bound to contact lenses.

PubMed

Dutta, Debarun; Cole, Nerida; Kumar, Naresh; Willcox, Mark D P

2013-01-07

To develop a stable antimicrobial contact lens, which is effective against the International Organization for Standardization (ISO) panel microorganisms, Acanthamoeba castellanii and drug resistant strains of Pseudomonas aeruginosa and Staphylococcus aureus. Melimine was covalently incorporated into etafilcon A lenses. The amount of peptide present on the lens surface was quantified using amino acid analysis. After coating, the heat stability (121°C), lens surface hydrophobicity (by captive bubble), and in vitro cytotoxicity to mouse L929 cells of the lenses were investigated. Antimicrobial activity against the micro-organisms was evaluated by viable plate count and fluorescence microscopy, measuring the proportion of cell death compared with control lenses with no melimine. The most effective concentration was determined to be 152 ± 44 μg lens(-1) melimine on the lens surface. After coating, lenses were relatively hydrophilic and were nontoxic to mammalian cells. The activity remained high after autoclaving (e.g., 3.1, 3.9, 1.2, and 1.0 log inhibition against P. aeruginosa, S. aureus, A. castellanii, and Fusarium solani, respectively). Fluorescence microscopy confirmed significantly reduced (P < 0.001) adhesion of viable bacteria to melimine contact lenses. Viable count confirmed that lenses were active against all the bacteria and fungi from the ISO panel, Acanthamoeba and gave at least 2 log inhibition against all the multidrug resistant S. aureus and P. aeruginosa strains. Melimine may offer excellent potential for development as a broad spectrum antimicrobial coating for contact lenses, showing activity against all the bacterial and fungal ISO panel microorganisms, Acanthamoeba, and antibiotic resistant strains of P. aeruginosa and S. aureus.

Metronidazole-triazole conjugates: Activity against Clostridium difficile and parasites

PubMed Central

Jarrad, Angie M.; Karoli, Tomislav; Debnath, Anjan; Tay, Chin Yen; Huang, Johnny X.; Kaeslin, Geraldine; Elliott, Alysha G.; Miyamoto, Yukiko; Ramu, Soumya; Kavanagh, Angela M.; Zuegg, Johannes; Eckmann, Lars; Blaskovich, Mark A.T.; Cooper, Matthew A.

2015-01-01

Metronidazole has been used clinically for over 50 years as an antiparasitic and broad-spectrum antibacterial agent effective against anaerobic bacteria. However resistance to metronidazole in parasites and bacteria has been reported, and improved second-generation metronidazole analogues are needed. The copper catalysed Huigsen azide-alkyne 1,3-dipolar cycloaddition offers a way to efficiently assemble new libraries of metronidazole analogues. Several new metronidazole-triazole conjugates (Mtz-triazoles) have been identified with excellent broad spectrum antimicrobial and antiparasitic activity targeting Clostridium difficile, Entamoeba histolytica and Giardia lamblia. Cross resistance to metronidazole was observed against stable metronidazole resistant C. difficile and G. lamblia strains. However for the most potent Mtz-triazoles, the activity remained in a therapeutically relevant window. PMID:26117821

Evaluation of Novel Antimicrobial Peptides as Topical Anti-Infectives with Broad Spectrum Activity Against Combat-Related Bacterial and Fungal Wound Infections

DTIC Science & Technology

2016-10-01

absence of topical antibiotics, are immediately colonized by gram -positive skin flora, such as Staphylococcus aureus. Gram -negative bacteria such as...complications. Silver sulfadiazine is not active against fungal infections,4 and its side effects include staining of the treated burn wound, allergic

Self-assembly of cationic multidomain peptide hydrogels: supramolecular nanostructure and rheological properties dictate antimicrobial activity

NASA Astrophysics Data System (ADS)

Jiang, Linhai; Xu, Dawei; Sellati, Timothy J.; Dong, He

2015-11-01

Hydrogels are an important class of biomaterials that have been widely utilized for a variety of biomedical/medical applications. The biological performance of hydrogels, particularly those used as wound dressing could be greatly advanced if imbued with inherent antimicrobial activity capable of staving off colonization of the wound site by opportunistic bacterial pathogens. Possessing such antimicrobial properties would also protect the hydrogel itself from being adversely affected by microbial attachment to its surface. We have previously demonstrated the broad-spectrum antimicrobial activity of supramolecular assemblies of cationic multi-domain peptides (MDPs) in solution. Here, we extend the 1-D soluble supramolecular assembly to 3-D hydrogels to investigate the effect of the supramolecular nanostructure and its rheological properties on the antimicrobial activity of self-assembled hydrogels. Among designed MDPs, the bactericidal activity of peptide hydrogels was found to follow an opposite trend to that in solution. Improved antimicrobial activity of self-assembled peptide hydrogels is dictated by the combined effect of supramolecular surface chemistry and storage modulus of the bulk materials, rather than the ability of individual peptides/peptide assemblies to penetrate bacterial cell membrane as observed in solution. The structure-property-activity relationship developed through this study will provide important guidelines for designing biocompatible peptide hydrogels with built-in antimicrobial activity for various biomedical applications.Hydrogels are an important class of biomaterials that have been widely utilized for a variety of biomedical/medical applications. The biological performance of hydrogels, particularly those used as wound dressing could be greatly advanced if imbued with inherent antimicrobial activity capable of staving off colonization of the wound site by opportunistic bacterial pathogens. Possessing such antimicrobial properties would also protect the hydrogel itself from being adversely affected by microbial attachment to its surface. We have previously demonstrated the broad-spectrum antimicrobial activity of supramolecular assemblies of cationic multi-domain peptides (MDPs) in solution. Here, we extend the 1-D soluble supramolecular assembly to 3-D hydrogels to investigate the effect of the supramolecular nanostructure and its rheological properties on the antimicrobial activity of self-assembled hydrogels. Among designed MDPs, the bactericidal activity of peptide hydrogels was found to follow an opposite trend to that in solution. Improved antimicrobial activity of self-assembled peptide hydrogels is dictated by the combined effect of supramolecular surface chemistry and storage modulus of the bulk materials, rather than the ability of individual peptides/peptide assemblies to penetrate bacterial cell membrane as observed in solution. The structure-property-activity relationship developed through this study will provide important guidelines for designing biocompatible peptide hydrogels with built-in antimicrobial activity for various biomedical applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr05233e

Antibacterial activity of combination of synthetic and biopolymer non-woven structures.

PubMed

Bhullar, Sukhwinder K; Özsel, Burcak Kaya; Yadav, Ramesh; Kaur, Ginpreet; Chintamaneni, Meena; Buttar, Harpal S

2015-12-01

Fibrous structures and synthetic polymer blends offer potential usages in making biomedical devices, textiles used in medical practices, food packaging, tissue engineering, environmental applications and biomedical arena. These products are also excellent candidates for building scaffolds to grow stem cells for implantation, to make tissue engineering grafts, to make stents to open up blood vessels caused by atherosclerosis or narrowed by blood clots, for drug delivery systems for micro- to nano-medicines, for transdermal patches, and for healing of wounds and burn care. The current study was designed to evaluate the antimicrobial activity of woven and non-woven forms of nano- and macro-scale blended polymers having biocompatible and biodegradable characteristics. The antimicrobial activity of non-woven fibrous structures created with the combination of synthetic and biopolymer was assessed using Gram-negative, Gram-positive bacteria, such as Staphylococcus aureus, Proteus vulgaris, Escherichia coli and Enterobacter aerogenes using pour plate method. Structural evaluation of the fabricated samples was performed by Fourier transform infrared spectroscopy. Broad spectrum antibacterial activities were found from the tested materials consisting of polyvinyl alcohol (PVA) with chitosan and nylon-6 combined with chitosan and formic acid. The combination of PVA with chitosan was more bactericidal or bacteriostatic than that of nylon-6 combined with chitosan and formic acid. PVA combination with chitosan appears to be a broad-spectrum antimicrobial agent.

Antibacterial and leishmanicidal activities of temporin-SHd, a 17-residue long membrane-damaging peptide.

PubMed

Abbassi, Feten; Raja, Zahid; Oury, Bruno; Gazanion, Elodie; Piesse, Christophe; Sereno, Denis; Nicolas, Pierre; Foulon, Thierry; Ladram, Ali

2013-02-01

Temporins are a family of short antimicrobial peptides (8-17 residues) that mostly show potent activity against Gram-positive bacteria. Herein, we demonstrate that temporin-SHd, a 17-residue peptide with a net charge of +2 (FLPAALAGIGGILGKLF(amide)), expressed a broad spectrum of antimicrobial activity. This peptide displayed potent antibacterial activities against Gram-negative and Gram-positive bacteria, including multi-drug resistant Staphylococcus aureus strains, as well as antiparasitic activity against promastigote and the intracellular stage (amastigote) of Leishmania infantum, at concentration not toxic for the macrophages. Temporin-SHd that is structured in a non-amphipathic α-helix in anionic membrane-mimetic environments, strongly and selectively perturbs anionic bilayer membranes by interacting with the polar head groups and acyl region of the phospholipids, with formation of regions of two coexisting phases: one phase rich in peptide and the other lipid-rich. The disruption of lipid packing within the bilayer may lead to the formation of transient pores and membrane permeation/disruption once a threshold peptide accumulation is reached. To our knowledge, Temporin-SHd represents the first known 17-residue long temporin expressing such broad spectrum of antimicrobial activity including members of the trypanosomatidae family. Additionally, since only a few shorter members (13 residues) of the temporin family are known to display antileishmanial activity (temporins-TA, -TB and -SHa), SHd is an interesting tool to analyze the antiparasitic mechanism of action of temporins. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Antibacterial Activity Affected by the Conformational Flexibility in Glycine-Lysine Based α-Helical Antimicrobial Peptides.

PubMed

Rončević, Tomislav; Vukičević, Damir; Ilić, Nada; Krce, Lucija; Gajski, Goran; Tonkić, Marija; Goić-Barišić, Ivana; Zoranić, Larisa; Sonavane, Yogesh; Benincasa, Monica; Juretić, Davor; Maravić, Ana; Tossi, Alessandro

2018-04-12

Antimicrobial peptides often show broad-spectrum activity due to a mechanism based on bacterial membrane disruption, which also reduces development of permanent resistance, a desirable characteristic in view of the escalating multidrug resistance problem. Host cell toxicity however requires design of artificial variants of natural AMPs to increase selectivity and reduce side effects. Kiadins were designed using rules obtained from natural peptides active against E. coli and a validated computational algorithm based on a training set of such peptides, followed by rational conformational alterations. In vitro activity, tested against ESKAPE strains (ATCC and clinical isolates), revealed a varied activity spectrum and cytotoxicity that only in part correlated with conformational flexibility. Peptides with a higher proportion of Gly were generally less potent and caused less bacterial membrane alteration, as observed by flow cytometry and AFM, which correlate to structural characteristics as observed by circular dichroism spectroscopy and predicted by molecular dynamics calculations.

Absorbent silver (I) antimicrobial fabrics

USDA-ARS?s Scientific Manuscript database

In recent years, silver in form of silver ions, has been gaining importance in the wound management as an effective broad-spectrum antimicrobial agent. Silver has a long history as an antimicrobial agent, especially in the treatment of wounds. Alginates and carboxymethyl (CM) cotton contain carboxyl...

Effect of Shufeng Jiedu capsules as a broad-spectrum antibacterial.

PubMed

Bao, Yanyan; Gao, Yingjie; Cui, Xiaolan

2016-02-01

This study sought to investigate the broad-spectrum antibacterial action of an alternative medicine, Shufeng Jiedu capsules (SFJDC). Antibacterial testing was performed to determine whether SFJDC had broad-spectrum antibacterial action in vitro, and testing was performed to verify whether SFJDC prevented death due to a Streptococcus or Staphylococcus aureus infection in mice. Results of antibacterial testing suggested that SFJDC are a broad-spectrum antibacterial and that SFJDC are superior to Lianhua Qingwen capsules as a broad-spectrum antibacterial. Results of testing revealed that SFJDC lowered the mortality rate, it reduced mortality, it increased average survival time, and it increased the lifespan of mice dying due to a Staphylococcus aureus or Streptococcus infection. Thus, SFJDC could become a complement to broad-spectrum antimicrobials in clinical settings.

Novel 4-Thiazolidinone Derivatives as Anti-Infective Agents: Synthesis, Characterization, and Antimicrobial Evaluation.

PubMed

Gupta, Amit; Singh, Rajendra; Sonar, Pankaj K; Saraf, Shailendra K

2016-01-01

A series of new 4-thiazolidinone derivatives was synthesized, characterized by spectral techniques, and screened for antimicrobial activity. All the compounds were evaluated against five Gram-positive bacteria, two Gram-negative bacteria, and two fungi, at concentrations of 50, 100, 200, 400, 800, and 1600 µg/mL, respectively. Minimum inhibitory concentrations of all the compounds were also determined and were found to be in the range of 100-400 µg/mL. All the compounds showed moderate-to-good antimicrobial activity. Compounds 4a [2-(4-fluoro-phenyl)-3-(4-methyl-5,6,7,8-tetrahydro-quinazolin-2-yl)-thiazolidin-4-one] and 4e [3-(4,6-dimethyl-pyrimidin-2-yl)-2-(2-methoxy-phenyl)-thiazolidin-4-one] were the most potent compounds of the series, exhibiting marked antimicrobial activity against Pseudomonas fluorescens, Staphylococcus aureus, and the fungal strains. Thus, on the basis of results obtained, it may be concluded that synthesized compounds exhibit a broad spectrum of antimicrobial activity.

Identification of didecyldimethylammonium salts and salicylic acid as antimicrobial compounds in commercial fermented radish kimchi.

PubMed

Li, Jing; Chaytor, Jennifer L; Findlay, Brandon; McMullen, Lynn M; Smith, David C; Vederas, John C

2015-03-25

Daikon radish (Raphanus sativus) fermented with lactic acid bacteria, especially Leuconostoc or Lactobacillus spp., can be used to make kimchi, a traditional Korean fermented vegetable. Commercial Leuconostoc/radish root ferment filtrates are claimed to have broad spectrum antimicrobial activity. Leuconostoc kimchii fermentation products are patented as preservatives for cosmetics, and certain strains of this organism are reported to produce antimicrobial peptides (bacteriocins). We examined the antimicrobial agents in commercial Leuconostoc/radish root ferment filtrates. Both activity-guided fractionation with Amberlite XAD-16 and direct extraction with ethyl acetate gave salicylic acid as the primary agent with activity against Gram-negative bacteria. Further analysis of the ethyl acetate extract revealed that a didecyldimethylammonium salt was responsible for the Gram-positive activity. The structures of these compounds were confirmed by a combination of (1)H- and (13)C NMR, high-performance liquid chromatography, high-resolution mass spectrometry, and tandem mass spectrometry analyses. Radiocarbon dating indicates that neither compound is a fermentation product. No antimicrobial peptides were detected.

Antimicrobial properties of cultivable bacteria associated with seaweeds in the Gulf of Mannar on the southeast coast of India.

PubMed

Thilakan, B; Chakraborty, K; Chakraborty, R D

2016-08-01

In this study, 234 bacterial strains were isolated from 7 seaweed species in the Gulf of Mannar on the southeast coast of India. The strains having consistent antimicrobial activity were chosen for further studies, and this constituted about 9.8% of the active strains isolated. Phylogenetic analysis using 16S rDNA sequencing with the help of classical biochemical identification indicated the existence of 2 major phyla, Firmicutes and Proteobacteria. Antimicrobial activity analysis combined with the results of amplifying genes encoding for polyketide synthetase and nonribosomal peptide synthetase showed that seaweed-associated bacteria had broad-spectrum antimicrobial activity. These epibionts might be beneficial to seaweeds by limiting or preventing the development of competing or fouling bacteria. Phylogenetic analysis of ketosynthase (KS) regions with respect to the diverse range of KS domains showed that the KS domains from the candidate isolates were of Type I. The bacterial cultures retained their antimicrobial activities after plasmid curing, which further suggested that the antimicrobial activity of these isolates was not encoded by plasmid, and the genes encoding the antimicrobial product might be present within the genome. Seaweed-associated bacteria with potential antimicrobial activity suggested that the seaweed species are an ideal ecological niche harboring specific bacterial diversity representing a largely underexplored source of antimicrobial secondary metabolites.

Phytochemical screening and in vitro antimicrobial activity of Thymus lanceolatus Desf. from Algeria

PubMed Central

Benbelaïd, Fethi; Khadir, Abdelmounaïm; Abdoune, Mohamed Amine; Bendahou, Mourad

2013-01-01

Objective To investigate the antimicrobial activity of an endemic Thyme, Thymus lanceolatus (T. lanceolatus), against a large number of pathogens. Methods Four solvent extracts were evaluated for antimicrobial activity using disc diffusion method and MIC determination on twenty-one strains. Results T. lanceolatus extracts showed a broad-spectrum antimicrobial activity, especially ethanol extract with inhibition zone diameters ranging from 14 to 32 mm, and MIC values from 0.052 to 0.500 mg/mL. Chloroform extract was more active against Gram-positive bacteria, since it has an inhibitory potency on Staphylococcus aureus and Enterococcus faecalis at only 31 µg/mL. While, hexane and water extracts were less effective since they were inactive against several strains. Conclusions The findings of this study indicate that T. lanceolatus has a strong antimicrobial potential, which justifies its use in folk medicine for treatment of infectious diseases. Since this species is poorly investigated, further refined studies on it pure secondary metabolites are needed and very important, in the perspective to identify new antimicrobial molecules from this endemic plant.

Preliminary phytochemical and antibacterial screening of Sesuvium portulacastrum in the United Arab Emirates.

PubMed

Al-Azzawi, Amad; Alguboori, Alyaa; Hachim, Mahmoud Y; Najat, M; Al Shaimaa, A; Sad, Maryam

2012-10-01

The present study describes the phytochemical profile and antimicrobial activity of Sesuvium portulacastrum. Three extracts of S. portulacastrum obtained by extraction in aqueous, ethanolic and dichloromethane solvents, respectively, were compared for their antimicrobial activity and ethanolic extract further subjected to gas chromatography-mass spectrometry (GC-MS) analysis to find out the nature of the compounds responsible for the antimicrobial activity. The antibacterial activities were assessed by measuring the diameter of the inhibition zones, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values. Compared to the aqueous and dichloromethane extract, the ethanolic extract showed better antimicrobial activity against Staphylococcus aureus and E. coli, indicating its potential application related to noscomial infections. GC-MS results revealed 22, 23-Dihydrostigmasterol, Benzoic acid, 3,4,5-trihydroxy-(Gallic acid), (2R,3R)-(-)-Epicatechin and Capsaicin in the ethanolic extract to be the molecules responsible for the antimicrobial activity of S. portulacastrum. To the best of our knowledge, this is the first report on analysis of antimicrobial components from S. portulacastrum in United Arab Emirates (UAE), and our results confer the utility of this plant extract in developing a novel broad spectrum antimicrobial agent.

Mode of Action of Lactoperoxidase as Related to Its Antimicrobial Activity: A Review

PubMed Central

Bafort, F.; Parisi, O.; Perraudin, J.-P.; Jijakli, M. H.

2014-01-01

Lactoperoxidase is a member of the family of the mammalian heme peroxidases which have a broad spectrum of activity. Their best known effect is their antimicrobial activity that arouses much interest in in vivo and in vitro applications. In this context, the proper use of lactoperoxidase needs a good understanding of its mode of action, of the factors that favor or limit its activity, and of the features and properties of the active molecules. The first part of this review describes briefly the classification of mammalian peroxidases and their role in the human immune system and in host cell damage. The second part summarizes present knowledge on the mode of action of lactoperoxidase, with special focus on the characteristics to be taken into account for in vitro or in vivo antimicrobial use. The last part looks upon the characteristics of the active molecule produced by lactoperoxidase in the presence of thiocyanate and/or iodide with implication(s) on its antimicrobial activity. PMID:25309750

High-throughput screening of a diversity collection using biodefense category A and B priority pathogens.

PubMed

Barrow, Esther W; Clinkenbeard, Patricia A; Duncan-Decocq, Rebecca A; Perteet, Rachel F; Hill, Kimberly D; Bourne, Philip C; Valderas, Michelle W; Bourne, Christina R; Clarkson, Nicole L; Clinkenbeard, Kenneth D; Barrow, William W

2012-08-01

One of the objectives of the National Institutes of Allergy and Infectious Diseases (NIAID) Biodefense Program is to identify or develop broad-spectrum antimicrobials for use against bioterrorism pathogens and emerging infectious agents. As a part of that program, our institution has screened the 10 000-compound MyriaScreen Diversity Collection of high-purity druglike compounds against three NIAID category A and one category B priority pathogens in an effort to identify potential compound classes for further drug development. The effective use of a Clinical and Laboratory Standards Institute-based high-throughput screening (HTS) 96-well-based format allowed for the identification of 49 compounds that had in vitro activity against all four pathogens with minimum inhibitory concentration values of ≤16 µg/mL. Adaptation of the HTS process was necessary to conduct the work in higher-level containment, in this case, biosafety level 3. Examination of chemical scaffolds shared by some of the 49 compounds and assessment of available chemical databases indicates that several may represent broad-spectrum antimicrobials whose activity is based on novel mechanisms of action.

CHARACTERIZATION OF A NARROW SPECTRUM ANTIMICROBIAL THAT EXHIBITS SPECIFIC ACTIVITY AGAINST UROPATHOGENIC BACTERIA

DTIC Science & Technology

2017-08-28

NARROW-SPECTRUM ANTIMICROBIAL THAT EXHIBITS SPECIFIC ACTIVITY AGAINST UROPATHOGENIC BACTERIA by Caitlin M. Barrows Courtney M. Cowell Jennifer...From - To) October 2015 – September 2016 4. TITLE AND SUBTITLE CHARACTERIZATION OF A NARROW-SPECTRUM ANTIMICROBIAL THAT EXHIBITS SPECIFIC ACTIVITY ...objective of the work described in this report is to identify a narrow-spectrum antimicrobial that exhibits targeted activity against uropathogenic

Synthesis of Some Benzofuran Derivatives Containing Pyrimidine Moiety as Potent Antimicrobial Agents.

PubMed

Venkatesh, Talavara; Bodke, Yadav Dasharathrao; Joy, Muthipeedika Nibin; Dhananjaya, Bhadrapura Lakkappa; Venkataraman, Sivaramakrishnan

2018-01-01

In this investigation, the synthesis of 2-substituted pyrimidines by the reaction of benzofuran chalcones (3a-d) with urea, thiourea and guanidine hydrochloride was reported. The structures of title compounds (4a-d), (5a-d) and (6a-d) were established on the basis of analytical and spectral data. The synthesized compounds were screened for antimicrobial activity and molecular docking studies. Some of the compounds displayed excellent antimicrobial activity. The molecular docking analysis revealed that compounds 5a and 5c with the lowest binding energy in comparison to others suggesting its potential as best inhibitor of GluN-6-P. Consequently, it is confirmed from the above analysis that the compounds 5a and 5c might serve as a useful backbone scaffold for rational design, adaptation and investigation of more active analogs as potential broad spectrum antimicrobial agents.

Bioprospecting of antimicrobial activity of extracts of endophytic fungi from Bauhinia guianensis.

PubMed

Pinheiro, Eduardo A A; Pina, Jeferson R S; Feitosa, André O; Carvalho, Josiwander M; Borges, Fábio C; Marinho, Patrícia S B; Marinho, Andrey M R

Antibiotic resistance results in higher medical costs, prolonged hospital stays and increased mortality and is rising to dangerously high levels in all parts of the world. Therefore, this study aims to search for new antimicrobial agents through bioprospecting of extracts of endophytic fungi from Bauhinia guianensis, a typical Amazonian plant used in combating infections. Seventeen (17) fungi were isolated and as result the methanolic extract of the fungus Exserohilum rostratum showed good activity against the bacteria tested. The polyketide monocerin was isolated by the chromatographic technique, identified by NMR and MS, showing broad antimicrobial spectrum. Copyright © 2016 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

In Vitro Assessment of the Antimicrobial Efficacy of Optimized Nitroglycerin-Citrate-Ethanol as a Nonantibiotic, Antimicrobial Catheter Lock Solution for Prevention of Central Line-Associated Bloodstream Infections

PubMed Central

Reitzel, Ruth A.; Hirsh-Ginsberg, Cheryl; Murray, Kimberly; Chaftari, Anne-Marie; Hachem, Ray; Raad, Issam

2016-01-01

The rapid, broad-spectrum, biofilm-eradicating activity of the combination of 0.01% nitroglycerin, 7% citrate, and 20% ethanol and its potential as a nonantibiotic, antimicrobial catheter lock solution (ACLS) were previously reported. Here, a nitroglycerin-citrate-ethanol (NiCE) ACLS optimized for clinical assessment was developed by reducing the nitroglycerin and citrate concentrations and increasing the ethanol concentration. Biofilm-eradicating activity was sustained when the ethanol concentration was increased from 20 to 22% which fully compensated for reducing the citrate concentration from 7% to 4% as well as the nitroglycerin concentration from 0.01% to 0.0015% or 0.003%. The optimized formulations demonstrated complete and rapid (2 h) eradication of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate Staphylococcus aureus (VISA), methicillin-resistant Staphylococcus epidermidis (MRSE), vancomycin-resistant enterococci (VRE), multidrug-resistant (MDR) Pseudomonas aeruginosa, MDR Klebsiella pneumoniae, MDR Enterobacter cloacae, MDR Acinetobacter baumannii, MDR Escherichia coli, MDR Stenotrophomonas maltophilia, Candida albicans, and Candida glabrata biofilms. The optimized NiCE lock solutions demonstrated anticoagulant activities comparable to those of heparin lock solutions. NiCE lock solution was significantly more effective than taurolidine-citrate-heparin lock solution in eradicating biofilms of Staphylococcus aureus and Candida glabrata. The optimized, nonantibiotic, heparin-free NiCE lock solution demonstrates rapid broad-spectrum biofilm eradication as well as effective anticoagulant activity, making NiCE a high-quality ACLS candidate for clinical assessment. PMID:27297475

Biosynthesis and Characterization of AgNPs–Silk/PVA Film for Potential Packaging Application

PubMed Central

Tao, Gang; Cai, Rui; Wang, Yejing; Song, Kai; Guo, Pengchao; Zhao, Ping; Zuo, Hua; He, Huawei

2017-01-01

Bionanocomposite packaging materials have a bright future for a broad range of applications in the food and biomedical industries. Antimicrobial packaging is one of the bionanocomposite packaging materials. Silver nanoparticle (AgNP) is one of the most attractive antimicrobial agents for its broad spectrum of antimicrobial activity against microorganisms. However, the traditional method of preparing AgNPs-functionalized packaging material is cumbersome and not environmentally friendly. To develop an efficient and convenient biosynthesis method to prepare AgNPs-modified bionanocomposite material for packaging applications, we synthesized AgNPs in situ in a silk fibroin solution via the reduction of Ag+ by the tyrosine residue of fibroin, and then prepared AgNPs–silk/poly(vinyl alcohol) (PVA) composite film by blending with PVA. AgNPs were synthesized evenly on the surface or embedded in the interior of silk/PVA film. The prepared AgNPs–silk/PVA film exhibited excellent mechanical performance and stability, as well as good antibacterial activity against both Gram-negative and Gram-positive bacteria. AgNPs–silk/PVA film offers more choices to be potentially applied in the active packaging field. PMID:28773026

Biosynthesis and Characterization of AgNPs-Silk/PVA Film for Potential Packaging Application.

PubMed

Tao, Gang; Cai, Rui; Wang, Yejing; Song, Kai; Guo, Pengchao; Zhao, Ping; Zuo, Hua; He, Huawei

2017-06-17

Bionanocomposite packaging materials have a bright future for a broad range of applications in the food and biomedical industries. Antimicrobial packaging is one of the bionanocomposite packaging materials. Silver nanoparticle (AgNP) is one of the most attractive antimicrobial agents for its broad spectrum of antimicrobial activity against microorganisms. However, the traditional method of preparing AgNPs-functionalized packaging material is cumbersome and not environmentally friendly. To develop an efficient and convenient biosynthesis method to prepare AgNPs-modified bionanocomposite material for packaging applications, we synthesized AgNPs in situ in a silk fibroin solution via the reduction of Ag⁺ by the tyrosine residue of fibroin, and then prepared AgNPs-silk/poly(vinyl alcohol) (PVA) composite film by blending with PVA. AgNPs were synthesized evenly on the surface or embedded in the interior of silk/PVA film. The prepared AgNPs-silk/PVA film exhibited excellent mechanical performance and stability, as well as good antibacterial activity against both Gram-negative and Gram-positive bacteria. AgNPs-silk/PVA film offers more choices to be potentially applied in the active packaging field.

In vitro antimicrobial activity of Medilox® super-oxidized water.

PubMed

Gunaydin, Murat; Esen, Saban; Karadag, Adil; Unal, Nevzat; Yanik, Keramettin; Odabasi, Hakan; Birinci, Asuman

2014-07-14

Super-oxidized water is one of the broad spectrum disinfectants, which was introduced recently. There are many researches to find reliable chemicals which are effective, inexpensive, easy to obtain and use, and effective for disinfection of microorganisms leading hospital infections. Antimicrobial activity of super-oxidized water is promising. The aim of this study was to investigate the in-vitro antimicrobial activity of different concentrations of Medilox® super-oxidized water that is approved by the Food and Drug Administration (FDA) as high level disinfectant. In this study, super-oxidized water obtained from Medilox® [Soosan E & C, Korea] device, which had been already installed in our hospital, was used. Antimicrobial activities of different concentrations of super-oxidized water (1/1, 1/2, 1/5, 1/10, 1/20, 1/50, 1/100) at different exposure times (1, 2, 5, 10, 30 min) against six ATCC strains, eight antibiotic resistant bacteria, yeasts and molds were evaluated using qualitative suspension test. Dey-Engley Neutralizing Broth [Sigma-Aldrich, USA] was used as neutralizing agent. Medilox® was found to be effective against all standard strains (Acinetobacter baumannii 19606, Escherichia coli 25922, Enterococcus faecalis 29212, Klebsiella pneumoniae 254988, Pseudomonas aeruginosa 27853, Staphylococcus aureus 29213), all clinical isolates (Acinetobacter baumannii, Escherichia coli, vancomycin-resistant Enterococcus faecium, Klebsiella pneumoniae, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, Bacillus subtilis, Myroides spp.), and all yeastsat 1/1 dilution in ≥1 minute. It was found to be effective on Aspergillus flavus at 1/1 dilution in ≥2 minutes and on certain molds in ≥5 minutes. Medilox® super-oxidized water is a broad spectrum, on-site producible disinfectant, which is effective on bacteria and fungi and can be used for the control of nosocomial infection.

Screening for antibacterial activity of some Turkish plants against fish pathogens: a possible alternative in the treatment of bacterial infections

PubMed Central

Turker, Hakan; Yıldırım, Arzu Birinci

2015-01-01

The antibacterial activity of ethanolic and aqueous crude extracts from 36 plants in Turkey, including seven endemic species, against fish pathogens was studied using the disc diffusion assay. The extract that was most active against all microbial strains, except Aeromonas salmonicida, was that of Dorycnium pentaphyllum. Some of the extracts also showed a very broad spectrum of potent antimicrobial activity. The extract of Anemone nemorosa showed the highest antimicrobial activity against Vibrio anguillarum. V. anguillarum, a Gram-negative bacterium, appeared to be the most susceptible to the plant extracts used in this experiment. To the best of our knowledge, this is the first report on the antimicrobial activity of 11 of the studied plants. The preliminary screening assay indicated that some of the Turkish plants with antibacterial properties may offer alternative therapeutic agents against bacterial infections in aquaculture industry. PMID:26019642

Povidone iodine in wound healing: A review of current concepts and practices.

PubMed

Bigliardi, Paul Lorenz; Alsagoff, Syed Abdul Latiff; El-Kafrawi, Hossam Yehia; Pyon, Jai-Kyong; Wa, Chad Tse Cheuk; Villa, Martin Anthony

2017-08-01

Of the many antimicrobial agents available, iodophore-based formulations such as povidone iodine have remained popular after decades of use for antisepsis and wound healing applications due to their favorable efficacy and tolerability. Povidone iodine's broad spectrum of activity, ability to penetrate biofilms, lack of associated resistance, anti-inflammatory properties, low cytotoxicity and good tolerability have been cited as important factors, and no negative effect on wound healing has been observed in clinical practice. Over the past few decades, numerous reports on the use of povidone iodine have been published, however, many of these studies are of differing design, endpoints, and quality. More recent data clearly supports its use in wound healing. Based on data collected through PubMed using specified search criteria based on above topics and clinical experience of the authors, this article will review preclinical and clinical safety and efficacy data on the use of povidone iodine in wound healing and its implications for the control of infection and inflammation, together with the authors' advice for the successful treatment of acute and chronic wounds. Povidone iodine has many characteristics that position it extraordinarily well for wound healing, including its broad antimicrobial spectrum, lack of resistance, efficacy against biofilms, good tolerability and its effect on excessive inflammation. Due to its rapid, potent, broad-spectrum antimicrobial properties, and favorable risk/benefit profile, povidone iodine is expected to remain a highly effective treatment for acute and chronic wounds in the foreseeable future. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Antagonistic lactic acid bacteria isolated from goat milk and identification of a novel nisin variant Lactococcus lactis

PubMed Central

2014-01-01

Background The raw goat milk microbiota is considered a good source of novel bacteriocinogenic lactic acid bacteria (LAB) strains that can be exploited as an alternative for use as biopreservatives in foods. The constant demand for such alternative tools justifies studies that investigate the antimicrobial potential of such strains. Results The obtained data identified a predominance of Lactococcus and Enterococcus strains in raw goat milk microbiota with antimicrobial activity against Listeria monocytogenes ATCC 7644. Enzymatic assays confirmed the bacteriocinogenic nature of the antimicrobial substances produced by the isolated strains, and PCR reactions detected a variety of bacteriocin-related genes in their genomes. Rep-PCR identified broad genetic variability among the Enterococcus isolates, and close relations between the Lactococcus strains. The sequencing of PCR products from nis-positive Lactococcus allowed the identification of a predicted nisin variant not previously described and possessing a wide inhibitory spectrum. Conclusions Raw goat milk was confirmed as a good source of novel bacteriocinogenic LAB strains, having identified Lactococcus isolates possessing variations in their genomes that suggest the production of a nisin variant not yet described and with potential for use as biopreservatives in food due to its broad spectrum of action. PMID:24521354

Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases.

PubMed

Citorik, Robert J; Mimee, Mark; Lu, Timothy K

2014-11-01

Current antibiotics tend to be broad spectrum, leading to indiscriminate killing of commensal bacteria and accelerated evolution of drug resistance. Here, we use CRISPR-Cas technology to create antimicrobials whose spectrum of activity is chosen by design. RNA-guided nucleases (RGNs) targeting specific DNA sequences are delivered efficiently to microbial populations using bacteriophage or bacteria carrying plasmids transmissible by conjugation. The DNA targets of RGNs can be undesirable genes or polymorphisms, including antibiotic resistance and virulence determinants in carbapenem-resistant Enterobacteriaceae and enterohemorrhagic Escherichia coli. Delivery of RGNs significantly improves survival in a Galleria mellonella infection model. We also show that RGNs enable modulation of complex bacterial populations by selective knockdown of targeted strains based on genetic signatures. RGNs constitute a class of highly discriminatory, customizable antimicrobials that enact selective pressure at the DNA level to reduce the prevalence of undesired genes, minimize off-target effects and enable programmable remodeling of microbiota.

Bioprospecting saline gradient of a Wildlife Sanctuary for bacterial diversity and antimicrobial activities.

PubMed

DeLuca, Mara; King, Riley; Morsy, Mustafa

2017-08-11

Antibiotic-resistant bacteria are becoming a global crisis, causing death of thousands of people and significant economic impact. The discovery of novel antibiotics is crucial to saving lives and reducing healthcare costs. To address the antibiotic-resistant crisis, in collaboration the Small World Initiative, which aims to crowdsource novel antibiotic discovery, this study aimed to identify antimicrobial producing bacteria and bacterial diversity in the soil of the Stimpson Wildlife Sanctuary, an inland area with a soil salt gradient. Approximately 4500 bacterial colonies were screened for antimicrobial activity and roughly 100 bacteria were identified as antimicrobial producers, which belong to Entrococcaceae (74%), Yersiniaceae (19%), and unidentified families (7%). Several bacterial isolates showed production of broad spectrum inhibitory compounds, while others were more specific to certain pathogens. The data obtained from the current study provide a resource for further characterization of the soil bacteria with antimicrobial activity, with an aim to discover novel ones. The study showed no correlation between soil salt level and the presence of bacteria with antimicrobial activities. However, most of the identified antimicrobial producing bacteria do not belong to actinomycetes, the most common phyla of antibiotic producing bacteria and this could potentially lead to the discovery of novel antibiotics.

Identification of a Signal That Mediates the Crosstalk Between Biosynthetic Gene Clusters for the Antibiotics 2,4-diacetylphloroglucinol and Pyoluteorin in Pseudomonas protegens Pf-5

USDA-ARS?s Scientific Manuscript database

Pseudomonas protegens Pf-5 produces a broad spectrum of secondary metabolites with anti-microbial activity. The production of two of these metabolites, 2,4-diacetylphloroglucinol (DAPG) and pyoluteorin, is coordinately regulated. Our previous study indicated that phloroglucinol, an intermediate in t...

Antimicrobial activity of southern African medicinal plants with dermatological relevance: From an ethnopharmacological screening approach, to combination studies and the isolation of a bioactive compound.

PubMed

Mabona, Unathi; Viljoen, Alvaro; Shikanga, Emmanual; Marston, Andrew; Van Vuuren, Sandy

2013-06-21

Ethnobotanical reports on more than 100 southern African medicinal plants with dermatological relevance have been highlighted, yet there is still limited scientific data to support claims for their antimicrobial effectiveness against skin pathogens. Guided by ethnobotanical data, this paper explores the antimicrobial efficacies of southern African medicinal plants used to treat skin ailments. To investigate the antimicrobial properties of southern African medicinal plants against dermatologically relevant pathogens. The study also aimed at providing a scientific rationale for the traditional use of plant combinations to treat skin diseases and the isolation of the bio-active compound from the most active species, Aristea ecklonii (Iridaceae). Organic and aqueous extracts (132) were prepared from 47 plant species and screened for antimicrobial properties against dermatologically relevant pathogens using the micro-titre plate dilution method. Four different plant combinations were investigated for interactive properties and the sum of the fractional inhibitory concentration (ƩFIC) calculated. Isobolograms were used to further investigate the antimicrobial interactive properties of Pentanisia prunelloides combined with Elephantorrhiza elephantina at varied ratios. A bioactivity-guided fractionation process was adopted to fractionate the organic leaf extract of Aristea ecklonii. Plants demonstrating notable broad-spectrum activities (MIC values ≤1.00mg/ml) against the tested pathogens included extracts from Aristea ecklonii, Chenopodium ambrosioides, Diospyros mespiliformis, Elephantorrhiza elephantina, Eucalyptus camaldulensis, Gunnera perpensa, Harpephyllum caffrum, Hypericum perforatum, Melianthus comosus, Terminalia sericea and Warburgia salutaris. The organic extract of Elephantorrhiza elephantina, a plant reportedly used to treat acne vulgaris, demonstrated noteworthy antimicrobial activity (MIC value of 0.05mg/ml) against Propionibacterium acnes. Similarly, Diospyros mespiliformis reported for its traditional use to treat ringworm, also displayed noteworthy antimicrobial activity against Trichophyton mentagrophytes (MIC 0.10mg/ml) and Microsporum canis (MIC 0.50mg/ml). The aqueous root extracts of Pentanisia prunelloides combined (1:1) with Elephantorrhiza elephantina displayed synergistic interactions (ƩFIC values 0.31-0.38) against Staphylococcus aureus, gentamycin-methicillin resistant Staphylococcus aureus, Staphylococcus epidermidis and Candida albicans. Fractionation of Aristea ecklonii resulted in the isolation of the known bio-active compound, plumbagin, displaying noteworthy antimicrobial activity (MIC range between 2.00μg/ml and 16.00μg/ml). Most of the plant extracts demonstrated pathogen specific antimicrobial effects with a few exhibiting broad-spectrum activities. Positive antimicrobial effects noted for plants such as Elephantorrhiza elephantina and Diospyros mespiliformis used for acne vulgaris and ringworm infections, respectively, give some validation to their reported traditiona l uses. Synergistic interactions noted for Pentanisia prunelloides combined with Elephantorrhiza elephantina validate an enhanced antimicrobial effect when used in combination. Noteworthy antimicrobial activities (MIC range between 2.00μg/ml and 16.00μg/ml) were observed for plumbagin isolated from Aristea ecklonii. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Resistance among Gram-negative ESKAPE pathogens isolated from hospitalized patients with intra-abdominal and urinary tract infections in Latin American countries: SMART 2013-2015.

PubMed

Karlowsky, James A; Hoban, Daryl J; Hackel, Meredith A; Lob, Sibylle H; Sahm, Daniel F

Gram-negative ESKAPE pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are important etiologic agents of nosocomial infection that are frequently resistant to broad-spectrum antimicrobial agents. Gram-negative ESKAPE pathogens were collected from hospitalized patients in 11 Latin American countries from 2013 to 2015 as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) global surveillance program. In total, 2113 isolates from intra-abdominal infections (IAI) and 970 isolates from urinary tract infections (UTI) were tested against antimicrobial agents using standardized CLSI broth microdilution methodology. Of the agents tested, amikacin demonstrated the highest rates of susceptibility (%) for K. pneumoniae (92.2, 92.3), Enterobacter spp. (97.5, 92.1), and P. aeruginosa (85.3, 75.2) isolates from both IAI and UTI, respectively. Ertapenem (68.5, 62.6) and imipenem (79.2, 75.9) showed substantially higher rates of susceptibility (%) than other β-lactams, including piperacillin-tazobactam (35.9, 37.4) against ESBL-positive isolates of K. pneumoniae from IAI and UTI, respectively. Rates of susceptibility to all agents tested against A. baumannii were ≤30.9%. Gram-negative ESKAPE pathogens isolated from Latin America demonstrated compromised in vitro susceptibility to commonly prescribed broad-spectrum, parenteral antimicrobial agents. Continued surveillance is warranted. New antimicrobial agents with potent activity against Gram-negative ESKAPE pathogens are urgently needed. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Appropriate antimicrobial therapy in the era of multidrug-resistant human pathogens.

PubMed

Pogue, J M; Kaye, K S; Cohen, D A; Marchaim, D

2015-04-01

The past decade has brought a significant rise in antimicrobial resistance, and the ESKAPE pathogens have become a significant threat to public health. Three epidemiological features that negatively impact patients, which are consistently seen with the ESKAPE pathogens, are the following: 1) there has been a rise in incidence of these organisms as causative human pathogens, 2) there has been a significant increase in antimicrobial resistance in these bacterial species, and 3) the infections caused by these resistant strains are associated with worse outcomes when compared with infections caused by their susceptible counterparts. Significant delays in time to appropriate antimicrobial therapy of up to 5 days have been reported in infections due to these organisms and this is the strongest predictor of mortality with ESKAPE pathogens, particular in critically ill patients, where every hour delay has an incremental survival disadvantage for patients. Strategies to decrease these delays are urgently needed. Although routine broad-spectrum empiric coverage for these organisms would ideally limit this delay, agents with activity against these organisms are sometimes less effective, have significant toxicity risk, and their use can result in the development of resistance. Therefore, strategies to optimize therapy, although limiting unnecessary use of broad-spectrum antimicrobials, are urgently needed. This review will discuss potential strategies to optimize empiric therapy in the age of multi-drug resistance, the limitations of these strategies, and will discuss future directions and opportunities. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Melanin-templated rapid synthesis of silver nanostructures

PubMed Central

2014-01-01

Background As a potent antimicrobial agent, silver nanostructures have been used in nanosensors and nanomaterial-based assays for the detection of food relevant analytes such as organic molecules, aroma, chemical contaminants, gases and food borne pathogens. In addition silver based nanocomposites act as an antimicrobial for food packaging materials. In this prospective, the food grade melanin pigment extracted from sponge associated actinobacterium Nocardiopsis alba MSA10 and melanin mediated synthesis of silver nanostructures were studied. Based on the present findings, antimicrobial nanostructures can be developed against food pathogens for food industrial applications. Results Briefly, the sponge associated actinobacterium N. alba MSA10 was screened and fermentation conditions were optimized for the production of melanin pigment. The Plackett-Burman design followed by a Box-Behnken design was developed to optimize the concentration of most significant factors for improved melanin yield. The antioxidant potential, reductive capabilities and physiochemical properties of Nocardiopsis melanin was characterized. The optimum production of melanin was attained with pH 7.5, temperature 35°C, salinity 2.5%, sucrose 25 g/L and tyrosine 12.5 g/L under submerged fermentation conditions. A highest melanin production of 3.4 mg/ml was reached with the optimization using Box-Behnken design. The purified melanin showed rapid reduction and stabilization of silver nanostructures. The melanin mediated process produced uniform and stable silver nanostructures with broad spectrum antimicrobial activity against food pathogens. Conclusions The melanin pigment produced by N. alba MSA10 can be used for environmentally benign synthesis of silver nanostructures and can be useful for food packaging materials. The characteristics of broad spectrum of activity against food pathogens of silver nanostructures gives an insight for their potential applicability in incorporation of food packaging materials and antimicrobials for stored fruits and foods. PMID:24885756

Antioxidant and antimicrobial activities of cinnamic acid derivatives.

PubMed

Sova, M

2012-07-01

Cinnamic acid is an organic acid occurring naturally in plants that has low toxicity and a broad spectrum of biological activities. In the search for novel pharmacologically active compounds, cinnamic acid derivatives are important and promising compounds with high potential for development into drugs. Many cinnamic acid derivatives, especially those with the phenolic hydroxyl group, are well-known antioxidants and are supposed to have several health benefits due to their strong free radical scavenging properties. It is also well known that cinnamic acid has antimicrobial activity. Cinnamic acid derivatives, both isolated from plant material and synthesized, have been reported to have antibacterial, antiviral and antifungal properties. Acids, esters, amides, hydrazides and related derivatives of cinnamic acid with such activities are here reviewed.

Broad-spectrum antibiotics in Norwegian hospitals.

PubMed

Holen, Øyunn; Alberg, Torunn; Blix, Hege Salvesen; Smith, Ingrid; Neteland, Marion Iren; Eriksen, Hanne Merete

2017-03-01

BACKGROUND One of the objectives in the action plan to reduce antimicrobial resistance in the health services in Norway is to reduce the use of broad-spectrum antibiotics in Norwegian hospitals. This study describes the use of certain broad-spectrum antibiotics mentioned in the action plan in Norwegian hospitals, and assesses prescribing practices in relation to the Norwegian guidelines for antibiotic use in hospitals.MATERIAL AND METHOD Data were analysed from a nationwide non-identifiable point prevalence survey in May 2016 where all systemic use of antibiotics was recorded.RESULTS Broad-spectrum antibiotics accounted for 33 % of all antibiotics prescribed. Altogether 84 % of all broad-spectrum antibiotics were prescribed as treatment, 8 % were for prophylactic use, and 8 % were classified as other/unknown. Lower respiratory tract infections were the most frequent indication for treatment with broad-spectrum antibiotics, involving 30 % of all broad-spectrum treatment.INTERPRETATION This point prevalence survey in Norwegian hospitals in spring 2016 indicates a possibility for reducing the use of broad-spectrum antibiotics in the treatment of lower respiratory tract infections and for prophylactic use. Reduction of healthcare-associated infections may also contribute.

Complete genome sequence of Lactobacillus plantarum LZ206, a potential probiotic strain with antimicrobial activity against food-borne pathogenic microorganisms.

PubMed

Li, Ping; Gu, Qing; Zhou, Qingqing

2016-11-20

Lactobacilli strains have been considered as important candidates for manufacturing "natural food", due to their antimicrobial properties and generally regarded as safe (GRAS) status. Lactobacillus plantarum LZ206 is a potential probiotic strain isolated from raw cow milk, with antimicrobial activity against various pathogens, including Gram-positive bacteria (Staphylococcus aureus and Listeria monocytogenes), Gram-negtive bacteria (Escherichia coli and Salmonella enterica), and fungus Candida albicans. To better understand molecular base for its antimicrobial activity, entire genome of LZ206 was sequenced. It was revealed that genome of LZ206 contained a circular 3,212,951-bp chromosome, two circular plasmids and one predicted linear plasmid. A plantaricin gene cluster, which is responsible for bacteriocins biosynthesis and could be associated with its broad-spectrum antimicrobial activity, was identified based on comparative genomic analysis. Whole genome sequencing of L. plantarum LZ206 might facilitate its applications to protect food products from pathogens' contamination in the dairy industry. Copyright © 2016 Elsevier B.V. All rights reserved.

Preliminary phytochemical screening and antimicrobial evaluation of three medicinal plants used in Nigeria.

PubMed

Baba, Haruna; Onanuga, Adebola

2011-01-01

Methanol extract of three Nigerian medicinal plants were screened for antimicrobial activity using modified Kirby-Bauer disc diffusion and agar dilution techniques to determine the diameters of zone of inhibition and minimum inhibitory concentrations (MIC) of the extracts respectively. The extract of each of the plants were tested against five clinical bacterial isolates comprising of two Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) and three Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumonia) organisms. All the extracts exhibited moderate to high level of antimicrobial activities against these microorganisms. Phytochemical screening of powdered plant material revealed the presence of some secondary metabolites such as alkaloids, saponins, tannins, anthraquinones and flavonoids. These Nigerian medicinal plants could be developed into cheap, safe and culturally acceptable standardized herbal products and may serve as a source of new molecules for broad-spectrum antimicrobial agents.

External immunity in ant societies: sociality and colony size do not predict investment in antimicrobials

PubMed Central

Halawani, Omar; Pearson, Bria; Mathews, Stephanie; López-Uribe, Margarita M.; Dunn, Robert R.; Smith, Adrian A.

2018-01-01

Social insects live in dense groups with a high probability of disease transmission and have therefore faced strong pressures to develop defences against pathogens. For this reason, social insects have been hypothesized to invest in antimicrobial secretions as a mechanism of external immunity to prevent the spread of disease. However, empirical studies linking the evolution of sociality with increased investment in antimicrobials have been relatively few. Here we quantify the strength of antimicrobial secretions among 20 ant species that cover a broad spectrum of ant diversity and colony sizes. We extracted external compounds from ant workers to test whether they inhibited the growth of the bacterium Staphylococcus epidermidis. Because all ant species are highly social, we predicted that all species would exhibit some antimicrobial activity and that species that form the largest colonies would exhibit the strongest antimicrobial response. Our comparative approach revealed that strong surface antimicrobials are common to particular ant clades, but 40% of species exhibited no antimicrobial activity at all. We also found no correlation between antimicrobial activity and colony size. Rather than relying on antimicrobial secretions as external immunity to control pathogen spread, many ant species have probably developed alternative strategies to defend against disease pressure. PMID:29515850

Comparison of Antibacterial Activity of Lactobacillus plantarum Strains Isolated from Two Different Kinds of Regional Cheeses from Poland: Oscypek and Korycinski Cheese

PubMed Central

Ołdak, Aleksandra; Rzepkowska, Anna

2017-01-01

Oscypek and korycinski are traditional Polish cheeses, exclusively produced in Tatra and in Podlasie region, respectively, produced from raw, unpasteurized milk. The 29 Lactobacillus plantarum strains were isolated on MRS agar from 12 cheese samples and used as a material for study. The main purpose of the work was to assess the antimicrobial properties and recognition of selected strains for the unique antagonistic activity and preservation role in food. It has been found that the highest antimicrobial activity was observed in the case of L. monocytogenes strains; however, the level of that activity was different depending on the Lb. plantarum strain. Strains from oscypek produced broad spectrum, and a few strains isolated from korycinski cheese produced a narrow spectrum of antimicrobial compounds, other than organic acids and hydrogen peroxide. Moreover, the antagonistic activity shown by Lb. plantarum strains is connected with the source from which a given strain was isolated. Strains isolated from oscypek cheese represented stronger activity against L. monocytogenes, whereas strains isolated from korycinski cheese were more active against E. coli. Strains Lb. plantarum Os13 and Kor14 could be considered as good candidates for protective cultures to extend durability of food products. PMID:28626762

Identifying priorities to improve paediatric in-hospital antimicrobial use by cross-sectional evaluation of prevalence and appropriateness of prescription.

PubMed

Goycochea-Valdivia, Walter Alfredo; Moreno-Ramos, Francisco; Paño-Pardo, José Ramón; Aracil-Santos, Francisco Javier; Baquero-Artigao, Fernando; Del Rosal-Rabes, Teresa; Mellado-Peña, María José; Escosa-García, Luis

2017-11-01

Information about paediatric in-hospital antimicrobial usage and prescribing patterns to guide improvement strategies is scant. We aim to use an evaluation of the prevalence and appropriateness of antimicrobial prescription to identify antimicrobial stewardship priorities in children. A cross-sectional point study was performed on hospitalised paediatric patients in a Spanish tertiary hospital, assessing the prevalence of antimicrobial prescription (PAP) and appropriateness of antimicrobial prescription (AAP). AAP was defined as a correct indication plus an appropriate prescribing pattern (dose, spectrum and interval). Evaluation was performed using established antimicrobial guidelines. Other factors that may have a bearing on antimicrobial prescription were also analysed. A total of 171 patients were included. PAP was 49.7% (85/171) and AAP was 60.9% (91/161). The most common indications for antimicrobial use were antimicrobial prophylaxis (28.3%, 32/113) and pneumonia (8.2%, 8/113). Overall, 161 antimicrobials were prescribed (1.9 antimicrobials per patient): 55.3% (89/161) were empiric, 16.1% (26/161) were targeted and 28.6% (46/161) were prophylactic. Amoxicillin/clavulanate (8.2%, 14/171) and sulfamethoxazole/trimethoprim (8.2%, 14/171) were the most prescribed antimicrobials. The prescription of antifungals (11.7%, 20/171) and antivirals (1.8%, 3/171) was analysed. Major causes of inappropriate antibiotic use were prolonged prescriptions (21.7%, 35/161) and use of agents with an excessively broad coverage spectrum (21.1%, 34/161). PAP and AAP varied between wards and antimicrobials. Measurement of PAP and AAP offers valuable information for detecting priorities in hospital settings and monitoring antimicrobial usage prior to the development of antimicrobial stewardship programmes. In our setting, the main areas for improvement are duration of therapy and proper use of broad-spectrum antimicrobials. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Antimicrobial Protection of Marsupial Pouch Young

PubMed Central

Cheng, Yuanyuan; Belov, Katherine

2017-01-01

Marsupials diverged from eutherian mammals about 148 million years ago and represent a unique lineage of mammals with distinctive morphological and reproductive characteristics. Marsupials have significantly shorter gestation periods than eutherians. Pregnancy typically ranges from 15 to 35 days, with young being born at a very early developmental stage and lacking differentiated lymphoid tissues and mature effector cells. Recent microbiome studies of the marsupial pouch revealed that marsupial young can face intense microbial challenges after birth, as the pouch contains a broad range of Gram-positive and Gram-negative bacteria. Antimicrobials are believed to play a significant role in the immune protection of marsupial newborns during their pouch life. The skin of the post-reproductive pouch secretes antimicrobial lysozyme and dermcidin, which may contribute to the decreased density of certain bacteria in the pouch. A range of antimicrobial agents, such as immunoglobulins, lysozyme, transferrin, and cathelicidins, have been identified in marsupial milk. Antimicrobial assays have revealed that marsupial cathelicidins have broad-spectrum activity against a variety of bacteria and fungi, including several multi-drug resistant strains. In this article, we will review the action mechanisms of these antimicrobial compounds and discuss how they protect marsupial newborns from potentially pathogenic bacteria inside the pouch. We will also discuss the potential of marsupial antimicrobial compounds as a source of novel antibiotics. PMID:28326070

An endogenous ribonuclease inhibitor regulates the antimicrobial activity of ribonuclease 7 in the human urinary tract

PubMed Central

Spencer, John David; Schwaderer, Andrew L.; Eichler, Tad; Wang, Huanyu; Kline, Jennifer; Justice, Sheryl S.; Cohen, Daniel M.; Hains, David S.

2013-01-01

Recent studies stress the importance of antimicrobial peptides in protecting the urinary tract from infection. Previously, we have shown that ribonuclease 7 (RNase 7) is a potent antimicrobial peptide that has broad-spectrum antimicrobial activity against uropathogenic bacteria. The urothelium of the lower urinary tract and intercalated cells of the kidney produce RNase 7 but regulation of its antimicrobial activity has not been well defined. Here we characterize the expression of an endogenous inhibitor, ribonuclease inhibitor (RI), in the urinary tract and evaluate its effect on RNase 7’s antimicrobial activity. Using RNA isolated from non-infected human bladder and kidney tissue, quantitative real-time PCR showed that RNH1, the gene encoding RI, is constitutively expressed throughout the urinary tract. With pyelonephritis, RNH1 expression and RI peptide production significantly decrease. Immunostaining localized RI production to the umbrella cells of the bladder and intercalated cells of the renal collecting tubule. In vitro assays showed that RI bound to RNase 7 and suppressed its antimicrobial activity by blocking its ability to bind the cell wall of uropathogenic bacteria. Thus, these results demonstrate a new immunomodulatory role for RI and identified a unique regulatory pathway that may affect how RNase 7 maintains urinary tract sterility. PMID:24107847

Polybrominated diphenyl ethers with potent and broad spectrum antimicrobial activity from the marine sponge Dysidea.

PubMed

Sun, Shi; Canning, Corene B; Bhargava, Kanika; Sun, Xiuxiu; Zhu, Wenjun; Zhou, Ninghui; Zhang, Yifan; Zhou, Kequan

2015-01-01

Three polybrominated diphenyl ethers, 2-(2',4'-dibromophenoxy)-3,5-dibromophenol (1) and 2-(2',4'-dibromophenoxy)-3,4,5-tribromophenol (2) were isolated from the marine sponge Dysidea granulosa; and 2-(2',4'-dibromophenoxy)-4,6-dibromophenol (3) from Dysidea spp. They exhibited potent and broad spectrum in vitro antibacterial activity, especially against methicillin resistant Staphylococcus aureus (MRSA), methicillin sensitive Staphylococcus aureus (MSSA), Escherichia coli O157:H7, and Salmonella. Minimal inhibitory concentration (MIC) was evaluated against 12 clinical and standard strains of Gram positive and negative bacteria. The observed MIC range was 0.1-4.0mg/L against all the Gram positive bacteria and 0.1-16.0mg/L against Gram negative bacteria. 2-(2',4″-Dibromophenoxy)-3,5-dibromophenol showed stronger broad spectrum antibacterial activity than other two compounds. 2-(2',4″-Dibromophenoxy)-3,5-dibromophenol and 2-(2',4'-dibromophenoxy)-4,6-dibromophenol are thermo-stable. The results suggest that 2-(2',4'-dibromophenoxy)-3,5-dibromophenol could be used as a potential lead molecule for anti-MRSA, anti-E. coli O157:H7, and anti-Salmonella for drug development. Copyright © 2015 Elsevier Ltd. All rights reserved.

In Vitro Assessment of the Antimicrobial Efficacy of Optimized Nitroglycerin-Citrate-Ethanol as a Nonantibiotic, Antimicrobial Catheter Lock Solution for Prevention of Central Line-Associated Bloodstream Infections.

PubMed

Reitzel, Ruth A; Rosenblatt, Joel; Hirsh-Ginsberg, Cheryl; Murray, Kimberly; Chaftari, Anne-Marie; Hachem, Ray; Raad, Issam

2016-09-01

The rapid, broad-spectrum, biofilm-eradicating activity of the combination of 0.01% nitroglycerin, 7% citrate, and 20% ethanol and its potential as a nonantibiotic, antimicrobial catheter lock solution (ACLS) were previously reported. Here, a nitroglycerin-citrate-ethanol (NiCE) ACLS optimized for clinical assessment was developed by reducing the nitroglycerin and citrate concentrations and increasing the ethanol concentration. Biofilm-eradicating activity was sustained when the ethanol concentration was increased from 20 to 22% which fully compensated for reducing the citrate concentration from 7% to 4% as well as the nitroglycerin concentration from 0.01% to 0.0015% or 0.003%. The optimized formulations demonstrated complete and rapid (2 h) eradication of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate Staphylococcus aureus (VISA), methicillin-resistant Staphylococcus epidermidis (MRSE), vancomycin-resistant enterococci (VRE), multidrug-resistant (MDR) Pseudomonas aeruginosa, MDR Klebsiella pneumoniae, MDR Enterobacter cloacae, MDR Acinetobacter baumannii, MDR Escherichia coli, MDR Stenotrophomonas maltophilia, Candida albicans, and Candida glabrata biofilms. The optimized NiCE lock solutions demonstrated anticoagulant activities comparable to those of heparin lock solutions. NiCE lock solution was significantly more effective than taurolidine-citrate-heparin lock solution in eradicating biofilms of Staphylococcus aureus and Candida glabrata The optimized, nonantibiotic, heparin-free NiCE lock solution demonstrates rapid broad-spectrum biofilm eradication as well as effective anticoagulant activity, making NiCE a high-quality ACLS candidate for clinical assessment. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Self-assembled cationic amphiphiles as antimicrobial peptides mimics: Role of hydrophobicity, linkage type, and assembly state.

PubMed

Zhang, Yingyue; Algburi, Ammar; Wang, Ning; Kholodovych, Vladyslav; Oh, Drym O; Chikindas, Michael; Uhrich, Kathryn E

2017-02-01

Inspired by high promise using naturally occurring antimicrobial peptides (AMPs) to treat infections caused by antimicrobial-resistant bacteria, cationic amphiphiles (CAms) were strategically designed as synthetic mimics to overcome associated limitations, including high manufacture cost and low metabolic stability. CAms with facially amphiphilic conformation were expected to demonstrate membrane-lytic properties and thus reduce tendency of resistance development. By systematically tuning the hydrophobicity, CAms with optimized compositions exhibited potent broad-spectrum antimicrobial activity (with minimum inhibitory concentrations in low μg/mL range) as well as negligible hemolytic activity. Electron microscope images revealed the morphological and ultrastructure changes of bacterial membranes induced by CAm treatment and validated their membrane-disrupting mechanism. Additionally, an all-atom molecular dynamics simulation was employed to understand the CAm-membrane interaction on molecular level. This study shows that these CAms can serve as viable scaffolds for designing next generation of AMP mimics as antimicrobial alternatives to combat drug-resistant pathogens. Copyright © 2016 Elsevier Inc. All rights reserved.

Synthesis and Characterization of Antimicrobial Nanomaterials

DTIC Science & Technology

2013-01-01

coatings have broad application in medical and food processing fields. Additional potential exists for active disinfection/decontamination processes as well...technique to form homogenous silica nanoparticles. The reaction also provides a method to entrap additional enzyme in silica matrices. When additional ...elucidate the mechanism of lysozyme-mediated silica formation.22 The biocidal spectrum of the material can be broadened by addition of other

Titanium surfaces immobilized with the major antimicrobial fragment FK-16 of human cathelicidin LL-37 are potent against multiple antibiotic-resistant bacteria.

PubMed

Mishra, Biswajit; Wang, Guangshun

2017-08-01

Infections on implanted medical devices are a challenging problem, especially when bacteria form difficult-to-treat biofilms. Antimicrobial peptides are considered to be a solution due to their potency against antibiotic-resistant superbugs. Previously, the authors' laboratory demonstrated the prevention of staphylococcal biofilm formation in an animal catheter model by injecting merecidin (formerly known as 17BIPHE2), a peptide engineered based on the only human cathelicidin. This study documents an alternative solution via covalent immobilization of FK-16, amino acid sequence FKRIVQRIKDFLRNLV-amide, which corresponds to the major antimicrobial region (residues 17-32) of LL-37. FK-16 is superior to the longer peptide LL-37 in terms of synthesis cost and the shorter peptide KR-12 in terms of activity spectrum. Indeed, the FK16-coated titanium surface showed a broad-spectrum activity against the ESKAPE pathogens, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. It also demonstrated anti-adhesion and biofilm inhibition capabilities against both S. aureus and E. coli.

Highly Stable Graphene-Based Nanocomposite (GO-PEI-Ag) with Broad-Spectrum, Long-Term Antimicrobial Activity and Antibiofilm Effects.

PubMed

Zhao, Rongtao; Kong, Wen; Sun, Mingxuan; Yang, Yi; Liu, Wanying; Lv, Min; Song, Shiping; Wang, Lihua; Song, Hongbin; Hao, Rongzhang

2018-05-30

Various silver nanoparticle (AgNP)-decorated graphene oxide (GO) nanocomposites (GO-Ag) have received increasing attention owing to their antimicrobial activity and biocompatibility; however, their aggregation in physiological solutions and the generally complex synthesis methods warrant improvement. This study aimed to synthesize a polyethyleneimine (PEI)-modified and AgNP-decorated GO nanocomposite (GO-PEI-Ag) through a facile approach through microwave irradiation without any extra reductants and surfactants; its antimicrobial activity was investigated on Gram-negative/-positive bacteria (including drug-resistant bacteria) and fungi. Compared with GO-Ag, GO-PEI-Ag acquired excellent stability in physiological solutions and electropositivity, showing substantially higher antimicrobial efficacy. Moreover, GO-PEI-Ag exhibited particularly excellent long-term effects, presenting no obvious decline in antimicrobial activity after 1 week storage in physiological saline and repeated use for three times and the lasting inhibition of bacterial growth in nutrient-rich culture medium. In contrast, GO-Ag exhibited a >60% decline in antimicrobial activity after storage. Importantly, GO-PEI-Ag effectively eliminated adhered bacteria, thereby preventing biofilm formation. The primary antimicrobial mechanisms of GO-PEI-Ag were evidenced as physical damage to the pathogen structure, causing cytoplasmic leakage. Hence, stable GO-PEI-Ag with robust, long-term antimicrobial activity holds promise in combating public-health threats posed by drug-resistant bacteria and biofilms.

Repurposing Auranofin, Ebselen, and PX-12 as Antimicrobial Agents Targeting the Thioredoxin System

PubMed Central

May, Holly C.; Yu, Jieh-Juen; Guentzel, M. N.; Chambers, James P.; Cap, Andrew P.; Arulanandam, Bernard P.

2018-01-01

As microbial resistance to drugs continues to rise at an alarming rate, finding new ways to combat pathogens is an issue of utmost importance. Development of novel and specific antimicrobial drugs is a time-consuming and expensive process. However, the re-purposing of previously tested and/or approved drugs could be a feasible way to circumvent this long and costly process. In this review, we evaluate the U.S. Food and Drug Administration tested drugs auranofin, ebselen, and PX-12 as antimicrobial agents targeting the thioredoxin system. These drugs have been shown to act on bacterial, fungal, protozoan, and helminth pathogens without significant toxicity to the host. We propose that the thioredoxin system could serve as a useful therapeutic target with broad spectrum antimicrobial activity. PMID:29556223

Recent advances in the chemistry and biology of carbapenem antibiotics.

PubMed

Coulton, S; Hunt, E

1996-01-01

The discovery of the olivanic acids and thienamycin aroused considerable interest amongst medicinal chemists and microbiologists around the world. The susceptibility of these agents to metabolic degradation has, however, been a major obstacle in their development. For many years the only notable success from such intensive research was the combination of imipenem with cilastatin, an inhibitor of the renal dipeptidase enzyme DHP-1. The enormous success of Primaxin for the treatment of a range of life-threatening bacterial infections provided the impetus for the discovery of totally synthetic, non-natural carbapenem derivatives that combine the broad spectrum of antimicrobial activity with stability to enzymatic degradation. This has indeed been realised in the development of meropenem; it possesses the broad spectrum of activity and resistance to beta-lactamases that are embodied in imipenem as well as displaying increased stability to human dehydropeptidases. Most recent research has focused upon the development of carbapenem antibiotics which combine broad spectrum antimicrobial activity and metabolic stability with oral absorption, for the treatment of community-acquired infections. Indeed, the pro-drug esters of the tricyclic carbapenems represent the first significant advance in this respect. However, the increased use of carbapenem antibiotics would undoubtedly accelerate the emergence of carbapenem-hydrolysing enzymes. The ultimate challenge could therefore be the design and synthesis of carbapenem derivatives that are resistant to these metallo-beta-lactamases. Due to the enormous problems encountered in the development of the carbapenem antibiotics, this area of research has, in the past, been described as a battlefield that did not bode well for the future [181]. Primaxin and meropenem proved however that these problems were not insurmountable, and are therefore a testimony to the persistence and dedication of those scientists in their war against bacterial infection.

In Vitro and In Vivo Activities of Antimicrobial Peptides Developed Using an Amino Acid-Based Activity Prediction Method

PubMed Central

Wu, Xiaozhe; Wang, Zhenling; Li, Xiaolu; Fan, Yingzi; He, Gu; Wan, Yang; Yu, Chaoheng; Tang, Jianying; Li, Meng; Zhang, Xian; Zhang, Hailong; Xiang, Rong; Pan, Ying; Liu, Yan; Lu, Lian

2014-01-01

To design and discover new antimicrobial peptides (AMPs) with high levels of antimicrobial activity, a number of machine-learning methods and prediction methods have been developed. Here, we present a new prediction method that can identify novel AMPs that are highly similar in sequence to known peptides but offer improved antimicrobial activity along with lower host cytotoxicity. Using previously generated AMP amino acid substitution data, we developed an amino acid activity contribution matrix that contained an activity contribution value for each amino acid in each position of the model peptide. A series of AMPs were designed with this method. After evaluating the antimicrobial activities of these novel AMPs against both Gram-positive and Gram-negative bacterial strains, DP7 was chosen for further analysis. Compared to the parent peptide HH2, this novel AMP showed broad-spectrum, improved antimicrobial activity, and in a cytotoxicity assay it showed lower toxicity against human cells. The in vivo antimicrobial activity of DP7 was tested in a Staphylococcus aureus infection murine model. When inoculated and treated via intraperitoneal injection, DP7 reduced the bacterial load in the peritoneal lavage solution. Electron microscope imaging and the results indicated disruption of the S. aureus outer membrane by DP7. Our new prediction method can therefore be employed to identify AMPs possessing minor amino acid differences with improved antimicrobial activities, potentially increasing the therapeutic agents available to combat multidrug-resistant infections. PMID:24982064

Dissection of the antimicrobial and hemolytic activity of Cap18: Generation of Cap18 derivatives with enhanced specificity.

PubMed

Ebbensgaard, Anna; Mordhorst, Hanne; Overgaard, Michael Toft; Aarestrup, Frank Møller; Hansen, Egon Bech

2018-01-01

Due to the rapid emergence of resistance to classical antibiotics, novel antimicrobial compounds are needed. It is desirable to selectively kill pathogenic bacteria without targeting other beneficial bacteria in order to prevent the negative clinical consequences caused by many broad-spectrum antibiotics as well as reducing the development of antibiotic resistance. Antimicrobial peptides (AMPs) represent an alternative to classical antibiotics and it has been previously demonstrated that Cap18 has high antimicrobial activity against a broad range of bacterial species. In this study we report the design of a positional scanning library consisting of 696 Cap18 derivatives and the subsequent screening for antimicrobial activity against Y. ruckeri, A. salmonicida, S. Typhimurium and L. lactis as well as for hemolytic activity measuring the hemoglobin release of horse erythrocytes. We show that the hydrophobic face of Cap18, in particular I13, L17 and I24, is essential for its antimicrobial activity against S. Typhimurium, Y. ruckeri, A. salmonicida, E. coli, P. aeruginosa, L. lactis, L. monocytogenes and E. faecalis. In particular, Cap18 derivatives harboring a I13D, L17D, L17P, I24D or I24N substitution lost their antimicrobial activity against any of the tested bacterial strains. In addition, we were able to generate species-specific Cap18 derivatives by particular amino acid substitutions either in the hydrophobic face at positions L6, L17, I20, and I27, or in the hydrophilic face at positions K16 and K18. Finally, our data showed the proline residue at position 29 to be essential for the inherent low hemolytic activity of Cap18 and that substitution of the residues K16, K23, or G21 by any hydrophobic residues enhances the hemolytic activity. This study demonstrates the potential of generating species-specific AMPs for the selective elimination of bacterial pathogens.

In Vivo, In Vitro, and In Silico Characterization of Peptoids as Antimicrobial Agents.

PubMed

Czyzewski, Ann M; Jenssen, Håvard; Fjell, Christopher D; Waldbrook, Matt; Chongsiriwatana, Nathaniel P; Yuen, Eddie; Hancock, Robert E W; Barron, Annelise E

2016-01-01

Bacterial resistance to conventional antibiotics is a global threat that has spurred the development of antimicrobial peptides (AMPs) and their mimetics as novel anti-infective agents. While the bioavailability of AMPs is often reduced due to protease activity, the non-natural structure of AMP mimetics renders them robust to proteolytic degradation, thus offering a distinct advantage for their clinical application. We explore the therapeutic potential of N-substituted glycines, or peptoids, as AMP mimics using a multi-faceted approach that includes in silico, in vitro, and in vivo techniques. We report a new QSAR model that we developed based on 27 diverse peptoid sequences, which accurately correlates antimicrobial peptoid structure with antimicrobial activity. We have identified a number of peptoids that have potent, broad-spectrum in vitro activity against multi-drug resistant bacterial strains. Lastly, using a murine model of invasive S. aureus infection, we demonstrate that one of the best candidate peptoids at 4 mg/kg significantly reduces with a two-log order the bacterial counts compared with saline-treated controls. Taken together, our results demonstrate the promising therapeutic potential of peptoids as antimicrobial agents.

Antimicrobial activity of nanoemulsion in combination with cetylpyridinium chloride in multidrug-resistant Acinetobacter baumannii.

PubMed

Hwang, Yoon Y; Ramalingam, Karthikeyan; Bienek, Diane R; Lee, Valerie; You, Tao; Alvarez, Rene

2013-08-01

Acinetobacter baumannii has emerged as a serious problematic pathogen due to the ever-increasing presence of antibiotic resistance, demonstrating a need for novel, broad-spectrum antimicrobial therapeutic options. Antimicrobial nanoemulsions are emulsified mixtures of detergent, oil, and water (droplet size, 100 to 800 nm) which have broad antimicrobial activity against bacteria, enveloped viruses, and fungi. Here, we screened the antimicrobial activities of five nanoemulsion preparations against four Acinetobacter baumannii isolates to identify the most suitable preparation for further evaluation. Among them, N5, which contains 10% (vol/vol) Triton X-100, 25% (vol/vol) soybean oil, and 1% (wt/vol) cetylpyridinium chloride (CPC), showed the best efficacy against A. baumannii in both its planktonic and biofilm forms and was selected for further study. Our data demonstrate that, while the killing of planktonic forms of A. baumannii was due to the 1% CPC component of our nanoemulsions, the breakdown of biofilms was achieved via the emulsified oil and detergent fractions. Furthermore, we documented the effect of ethanol and NaCl in combination with N5 on planktonic A. baumannii. In killing curves of N5 combined with other agents (ethanol or NaCl), a synergistic effect of a ≥ 2-log decrease in CFU/ml was observed. The antibiofilm activity of N5 was confirmed via a cell proliferation test and scanning electron microscopy. The effects of exposure to severe environmental conditions, which simulates the field conditions in Iraq and Afghanistan, were evaluated, and this exposure did not affect the overall antimicrobial activity of N5. These studies lay a solid foundation for the utilization of nanoemulsions against the antibiotic-resistant forms of A. baumannii.

Antimicrobial Activity of Nanoemulsion in Combination with Cetylpyridinium Chloride in Multidrug-Resistant Acinetobacter baumannii

PubMed Central

Hwang, Yoon Y.; Ramalingam, Karthikeyan; Bienek, Diane R.; Lee, Valerie; You, Tao

2013-01-01

Acinetobacter baumannii has emerged as a serious problematic pathogen due to the ever-increasing presence of antibiotic resistance, demonstrating a need for novel, broad-spectrum antimicrobial therapeutic options. Antimicrobial nanoemulsions are emulsified mixtures of detergent, oil, and water (droplet size, 100 to 800 nm) which have broad antimicrobial activity against bacteria, enveloped viruses, and fungi. Here, we screened the antimicrobial activities of five nanoemulsion preparations against four Acinetobacter baumannii isolates to identify the most suitable preparation for further evaluation. Among them, N5, which contains 10% (vol/vol) Triton X-100, 25% (vol/vol) soybean oil, and 1% (wt/vol) cetylpyridinium chloride (CPC), showed the best efficacy against A. baumannii in both its planktonic and biofilm forms and was selected for further study. Our data demonstrate that, while the killing of planktonic forms of A. baumannii was due to the 1% CPC component of our nanoemulsions, the breakdown of biofilms was achieved via the emulsified oil and detergent fractions. Furthermore, we documented the effect of ethanol and NaCl in combination with N5 on planktonic A. baumannii. In killing curves of N5 combined with other agents (ethanol or NaCl), a synergistic effect of a ≥2-log decrease in CFU/ml was observed. The antibiofilm activity of N5 was confirmed via a cell proliferation test and scanning electron microscopy. The effects of exposure to severe environmental conditions, which simulates the field conditions in Iraq and Afghanistan, were evaluated, and this exposure did not affect the overall antimicrobial activity of N5. These studies lay a solid foundation for the utilization of nanoemulsions against the antibiotic-resistant forms of A. baumannii. PMID:23669390

A novel antimicrobial peptide against dental-caries-associated bacteria.

PubMed

Chen, Long; Jia, Lili; Zhang, Qiang; Zhou, Xirui; Liu, Zhuqing; Li, Bingjie; Zhu, Zhentai; Wang, Fenwei; Yu, Changyuan; Zhang, Qian; Chen, Feng; Luo, Shi-Zhong

2017-10-01

Dental caries, a highly prevalent oral disease, is primarily caused by pathogenic bacteria infection, and most of them are anaerobic. Herein, we investigated the activity of a designed antimicrobial peptide ZXR-2, and found it showed broad-spectrum activity against a variety of Gram-positive and Gram-negative oral bacteria, particularly the caries-related taxa Streptococcus mutans. Time-course killing assays indicated that ZXR-2 killed most bacterial cells within 5 min at 4 × MIC. The mechanism of ZXR-2 involved disruption of cell membranes, as observed by scanning electron microscopy. Moreover, ZXR-2 inhibited the formation of S. mutans biofilm, but showed limited hemolytic effect. Based on its potent antimicrobial activity, rapid killing, and inhibition of S. mutans biofilm formation, ZXR-2 represents a potential therapeutic for the prevention and treatment of dental caries. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identification, Characterization, Immunolocalization, and Biological Activity of Lucilin Peptide.

PubMed

Alberto, Tellez German; Alejandra, Zapata Jesica; Johanna, Toro Lily; Carolina, Henao Diana; Pablo, Bedoya Juan; David, Rivera Juan; Valentin, Trujillo Juan; Bruno, Rivas; Lopez, Richard Onalbi Hoyos; Carlos, Castano Jhon

2018-06-08

Maggots from the Lucilia sp. genus are used for debridement of infected and necrotic wounds. Broad-spectrum antimicrobial activity has been described in the excretion/secretions (ES 1 ) of these larvae. This study identifies the genetic sequence of a cecropin-like antimicrobial peptide from Lucilia eximia. Total RNA was extracted and used for PCR-RACE amplification of a cecropin, the native peptide was immunolocalized in the tissues and secretions of the larvae, and a synthetic analog was used to explore its antimicrobial, cytotoxic, LPS neutralizing and wound-healing activities in vitro. The genetic cDNA sequence of a cecropin-like antimicrobial peptide in L. eximia called "Lucilin" was amplified, corresponding to 63 aa completed protein and 40 aa mature peptide; the structure of the mature peptide was predicted as an α-helix. The peptide was immunolocalized in the salivary glands, fat body, the ES, and hemolymph of the maggots. Lucilin synthetic peptide analog was active against E. coli DH10B with a MIC 2 of 7.8 µg/mL, E. coli extended spectrum b-lactamase (ESBL) (MIC: 15.6 µg/mL), and Enterobacter cloacae (MIC: 125 µg/mL), but it was not active against Pseudomonas aeruginosa and Staphylococcus epidermidis; and had no cytotoxic or hemolytic activity. It showed immunomodulatory activity against human peripheral blood mononuclear cells (PBMCs) stimulated with LPS, reducing the TNF-α production when treated at 17 µg/mL and induces cell migration of Hacat at 5 and 50 µg/mL. Lucilin is a cecropin-like peptide from L. eximia with antimicrobial activity against Gram negative bacteria and immunomodulatory activities, decreasing the TNF-α production in PBMCs and inducing cellular migration in human keratinocytes. Copyright © 2018. Published by Elsevier B.V.

Extended stability of antimicrobial agents in administration devices.

PubMed

Jenkins, Abi; Hills, Tim; Santillo, Mark; Gilchrist, Mark

2017-04-01

Outpatient parenteral antimicrobial therapy (OPAT) is an established approach to patient care. A lack of data on antimicrobial stability within administration devices is a barrier to service expansion, and poses an antimicrobial stewardship dilemma. Often broad-spectrum, long half-life agents are used instead of narrow-spectrum agents, which need more frequent administration, but could possibly be used if stability data were available. To complete a comprehensive literature review of published antimicrobial stability data, and assess these against a nationally recognized minimum dataset for medicines compounded into administration devices. Medline, EMBASE, Global Health, International Pharmaceutical Abstracts and Biomedical Research Database were interrogated in April 2014 and updated in November 2015. A total of 420 citations were reviewed with 121 selected for full text review. None of these papers met the inclusion criteria stipulated in the national standards. The most frequent reason for study exclusion was the tolerance limit for the level of the active pharmaceutical ingredient being wider than 95%-105% and absence of 'in-use' testing at 37 °C. This review found no published studies that comply with UK national standards for stability testing. We recommend further research and publication of antimicrobial stability data to support OPAT within the antimicrobial stewardship agenda. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Efficacy of enterocin S760 in treatment of mice with anthrax infection due to Bacillus anthracis M-71].

PubMed

Svetoch, E A; Borzilov, A I; Eruslanov, B V; Korobova, O V; Kombarova, T I; Levchuk, V P; Teĭmurazov, M G; Stepanshin, Iu G; Marinin, L I; Diatlov, I A

2011-01-01

The therapeutic efficacy of enterocin S760, a broad spectrum antimicrobial peptide produced by Enterococcus faecium LWP760 was tested on mice infected with Bacillus anthracis M-71 to induce anthrax (second Tsenkovsky's vaccine). Intraperitoneal four-, two- or one-fold administration of the peptide in a dose of 25 mg/kg for 10 days for prophylactic (1 hour after the contamination) and therapeutic (24 hours after the contamination) purposes prevented or cured the infection in 90-100% of the mice versus the 100-percent lethality in the control (untreated animals). The antimicrobial activity of enterocin S760 against B. anthracis M-71 in vivo correlated with activity in vitro. Enterocin S760 is considered a novel promising antimicrobial for the treatment of grampositive and gramnegative infections.

Occurrence of antimicrobial resistance in bacteria from diagnostic samples from dogs.

PubMed

Pedersen, Karl; Pedersen, Kristina; Jensen, Helene; Finster, Kai; Jensen, Vibeke F; Heuer, Ole E

2007-10-01

To study the occurrence of antimicrobial resistance among common bacterial pathogens from dogs and relate resistance patterns to data on consumption of antimicrobials. The antimicrobial susceptibility patterns of 201 Staphylococcus intermedius, 37 Streptococcus canis, 39 Pseudomonas aeruginosa, 25 Pasteurella multocida, 29 Proteus spp. and 449 Escherichia coli isolates from clinical submissions from dogs were determined by a broth-dilution method for determination of minimal inhibitory concentration. Data for consumption of antimicrobials were retrieved from VetStat, a national database for reporting antimicrobial prescriptions. The majority of the antimicrobials prescribed for dogs were broad-spectrum compounds, and extended-spectrum penicillins, cephalosporins and sulphonamides + trimethoprim together accounted for 81% of the total amount used for companion animals. Resistance to cephalosporins and amoxicillin with clavulanic acid was very low for all bacterial species examined, except for P. aeruginosa, and resistance to sulphonamides and trimethoprim was low for most species. Among the S. intermedius isolates, 60.2% were resistant to penicillin, 30.2% to fusidic acid and 27.9% to macrolides. Among E. coli isolates, the highest level of resistance was recorded for ampicillin, sulphonamides, trimethoprim, tetracyclines and streptomycin. Certain differences in resistance patterns between isolates from different sites or organs were noticed for E. coli, S. intermedius and Proteus isolates. This investigation provided data on occurrence of antimicrobial resistance in important pathogenic bacteria from dogs, which may be useful for the small animal practitioner. Resistance was low to the compounds that were most often used, but unfortunately, these compounds were broad-spectrum. Data on resistance and usage may form a background for the establishment of a set of recommendations for prudent use of antimicrobials for companion animals.

Cationic host defense peptides; novel antimicrobial therapeutics against Category A pathogens and emerging infections

PubMed Central

Findlay, Fern; Proudfoot, Lorna; Stevens, Craig

2016-01-01

Cationic Host Defense Peptides (HDP, also known as antimicrobial peptides) are crucial components of the innate immune system and possess broad-spectrum antibacterial, antiviral, and immunomodulatory activities. They can contribute to the rapid clearance of biological agents through direct killing of the organisms, inhibition of pro-inflammatory mediators such as lipopolysaccharide, and by modulating the inflammatory response to infection. Category A biological agents and materials, as classified by the United States National Institutes for Health, the US Centers for Disease Control and Prevention, and the US Department of Homeland Security, carry the most severe threat in terms of human health, transmissibility, and preparedness. As such, there is a pressing need for novel frontline approaches for prevention and treatment of diseases caused by these organisms, and exploiting the broad antimicrobial activity exhibited by cationic host defense peptides represents an exciting priority area for clinical research. This review will summarize what is known about the antimicrobial and antiviral effects of the two main families of cationic host defense peptides, cathelicidins, and defensins in the context of Category A biological agents which include, but are not limited to; anthrax (Bacillus anthracis), plague (Yersinia pestis), smallpox (Variola major), tularemia (Francisella tularensis). In addition, we highlight priority areas, particularly emerging viral infections, where more extensive research is urgently required. PMID:27315342

Cationic host defense peptides; novel antimicrobial therapeutics against Category A pathogens and emerging infections.

PubMed

Findlay, Fern; Proudfoot, Lorna; Stevens, Craig; Barlow, Peter G

2016-01-01

Cationic Host Defense Peptides (HDP, also known as antimicrobial peptides) are crucial components of the innate immune system and possess broad-spectrum antibacterial, antiviral, and immunomodulatory activities. They can contribute to the rapid clearance of biological agents through direct killing of the organisms, inhibition of pro-inflammatory mediators such as lipopolysaccharide, and by modulating the inflammatory response to infection. Category A biological agents and materials, as classified by the United States National Institutes for Health, the US Centers for Disease Control and Prevention, and the US Department of Homeland Security, carry the most severe threat in terms of human health, transmissibility, and preparedness. As such, there is a pressing need for novel frontline approaches for prevention and treatment of diseases caused by these organisms, and exploiting the broad antimicrobial activity exhibited by cationic host defense peptides represents an exciting priority area for clinical research. This review will summarize what is known about the antimicrobial and antiviral effects of the two main families of cationic host defense peptides, cathelicidins, and defensins in the context of Category A biological agents which include, but are not limited to; anthrax (Bacillus anthracis), plague (Yersinia pestis), smallpox (Variola major), tularemia (Francisella tularensis). In addition, we highlight priority areas, particularly emerging viral infections, where more extensive research is urgently required.

Avian host defense peptides.

PubMed

Cuperus, Tryntsje; Coorens, Maarten; van Dijk, Albert; Haagsman, Henk P

2013-11-01

Host defense peptides (HDPs) are important effector molecules of the innate immune system of vertebrates. These antimicrobial peptides are also present in invertebrates, plants and fungi. HDPs display broad-spectrum antimicrobial activities and fulfill an important role in the first line of defense of many organisms. It is becoming increasingly clear that in the animal kingdom the functions of HDPs are not confined to direct antimicrobial actions. Research in mammals has indicated that HDPs have many immunomodulatory functions and are also involved in other physiological processes ranging from development to wound healing. During the past five years our knowledge about avian HDPs has increased considerably. This review addresses our current knowledge on the evolution, regulation and biological functions of HDPs of birds. Copyright © 2013 Elsevier Ltd. All rights reserved.

Newly Isolated Paenibacillus tyrfis sp. nov., from Malaysian Tropical Peat Swamp Soil with Broad Spectrum Antimicrobial Activity

PubMed Central

Aw, Yoong-Kit; Ong, Kuan-Shion; Lee, Learn-Han; Cheow, Yuen-Lin; Yule, Catherine M.; Lee, Sui-Mae

2016-01-01

Emergence of antimicrobial resistance coupled with the slowdown in discovery of new antimicrobial compounds points to serious consequences for human health. Therefore, scientists are looking for new antimicrobial compounds from unique and understudied ecosystems such as tropical peat swamp forests. Over the course of isolating antimicrobial producing bacteria from North Selangor tropical peat swamp forest, Malaysia, a Gram variable, rod shaped, endospore forming, facultative anaerobic novel strain MSt1T that exerts potent and broad spectrum antimicrobial activity was isolated. Phylogenetic analysis using 16S rRNA gene sequences showed that strain MSt1T belonged to the genus Paenibacillus with the highest similarity to Paenibacillus elgii SD17T (99.5%). Whole genome comparison between strain MSt1T with its closely related species using average nucleotide identity (ANI) revealed that similarity between strain MSt1T with P. elgii B69 (93.45%) and Paenibacillus ehimensis A2 (90.42%) was below the recommended threshold of 95%. Further analysis using in silico pairwise DDH also showed that similarity between strain MSt1T with P. elgii B69 (55.4%) and P. ehimensis A2 (43.7%) was below the recommended threshold of 70%. Strain MSt1T contained meso-diaminopilemic acid in the cell wall and MK-7 as the major menaquinone. The major fatty acids of strain MSt1T were anteiso-C15:0 (48.2%) and C16:0 (29.0%) whereas the polar lipid profile consisted of phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, one unknown lipid, two unknown glycolipids, and one unknown phospholipid. Total DNA G+C content of strain MSt1T was 51.5 mol%. The extract from strain MSt1T exerted strong antimicrobial activity against Escherichia coli ATCC 25922 (MIC = 1.5 μg/mL), MRSA ATCC 700699 (MIC = 25 μg/mL) and Candida albicans IMR (MIC = 12.5 μg/mL). Partially purified active fraction exerted a strong effect against E. coli ATCC 25922 resulting in cell rupture when viewed with SEM. Based on distinctive taxonomic differences between strain MSt1T when compared to its closely related type species, we propose that strain MSt1T represents a novel species within the genus of Paenibacillus, for which the name Paenibacillus tyrfis sp. nov. (= DSM 100708T = MCCC 1K01247T) is proposed. PMID:26973605

Modified lysozymes as novel broad spectrum natural antimicrobial agents in foods.

PubMed

Aminlari, Ladan; Hashemi, Marjan Mohammadi; Aminlari, Mahmoud

2014-06-01

In recent years much attention and interest have been directed toward application of natural antimicrobial agents in foods. Some naturally occurring proteins such as lactoperoxidase, lactoferrin, and lysozyme have received considerable attention and are being considered as potential antimicrobial agents in foods. Lysozyme kills bacteria by hydrolyzing the peptidoglycan layer of the cell wall of certain bacterial species, hence its application as a natural antimicrobial agent has been suggested. However, limitations in the action of lysozyme against only Gram-positive bacteria have prompted scientists to extend the antimicrobial effects of lysozyme by several types of chemical modifications. During the last 2 decades extensive research has been directed toward modification of lysozyme in order to improve its antimicrobial properties. This review will report on the latest information available on lysozyme modifications and examine the applicability of the modified lysozymes in controlling growth of Gram-positive and Gram-negative bacteria in foods. The results of modifications of lysozyme using its conjugation with different small molecule, polysaccharides, as well as modifications using proteolytic enzymes will be reviewed. These types of modifications have not only increased the functional properties of lysozyme (such as solubility and heat stability) but also extended the antimicrobial activity of lysozyme. Many examples will be given to show that modification can decrease the count of Gram-negative bacteria in bacterial culture and in foods by as much as 5 log CFU/mL and in some cases essentially eliminated Escherichia coli. In conclusion this review demonstrates that modified lysozymes are excellent natural food preservatives, which can be used in food industry. The subject described in this review article can lead to the development of methods to produce new broad-spectrum natural antimicrobial agents, based on modification of chicken egg white lysozyme, which might potentially replace the currently used synthetic food preservatives. © 2014 Institute of Food Technologists®

Antimicrobial Peptides from Fish

PubMed Central

Masso-Silva, Jorge A.; Diamond, Gill

2014-01-01

Antimicrobial peptides (AMPs) are found widely distributed through Nature, and participate in the innate host defense of each species. Fish are a great source of these peptides, as they express all of the major classes of AMPs, including defensins, cathelicidins, hepcidins, histone-derived peptides, and a fish-specific class of the cecropin family, called piscidins. As with other species, the fish peptides exhibit broad-spectrum antimicrobial activity, killing both fish and human pathogens. They are also immunomodulatory, and their genes are highly responsive to microbes and innate immuno-stimulatory molecules. Recent research has demonstrated that some of the unique properties of fish peptides, including their ability to act even in very high salt concentrations, make them good potential targets for development as therapeutic antimicrobials. Further, the stimulation of their gene expression by exogenous factors could be useful in preventing pathogenic microbes in aquaculture. PMID:24594555

Butyrate enhances disease resistance of chickens by inducing antimicrobial host defense peptide gene expression

USDA-ARS?s Scientific Manuscript database

Host defense peptides (HDPs) constitute a large group of natural broad-spectrum antimicrobials and an important first line of immunity in virtually all forms of life. Specific augmentation of synthesis of endogenous HDPs may represent a promising antibiotic-alternative approach to disease control. I...

Antibacterial activity of alkaloids produced by endophytic fungus Aspergillus sp. EJC08 isolated from medical plant Bauhinia guianensis.

PubMed

Pinheiro, Eduardo Antonio A; Carvalho, Josiwander Miranda; dos Santos, Diellem Cristina P; Feitosa, André de Oliveira; Marinho, Patrícia Santana B; Guilhon, Giselle Maria Skelding Pinheiro; de Souza, Afonso Duarte L; da Silva, Felipe Moura A; Marinho, Andrey Moacir do R

2013-01-01

Bauhinia guianensis is a typical plant in the Amazon region belonging to the family Leguminosea, used by local populations for the treatment of infectious and renal diseases. Previous work on the plant B. guianensis led to the isolation of substances with anti-inflammatory and analgesic activities. Thus, compounds isolated from B. guianensis with antimicrobial activities had not been identified. Given that there is a possibility of biological activity reported for a given plant being found in the endophytic fungi, we decided to isolate endophytic fungi from B. guianensis and test their antimicrobial activities. The alkaloids known as fumigaclavine C and pseurotin A were isolated by column chromatography and identified by 1D and 2D NMR techniques and mass spectrometry. The alkaloids are first reported as broad-spectrum antibacterial agents with good activity.

Recent approaches in design of peptidomimetics for antimicrobial drug discovery research.

PubMed

Lohan, Sandeep; Bisht, Gopal Singh

2013-06-01

Resistant pathogenic microbial strains are emerging at a rate that far exceeds the pace of new anti-infective drug development. In order to combat resistance development, there is pressing need to develop novel class of antibiotics having different mechanism of action in comparison to existing antibiotics. Antimicrobial peptides (AMPs) have been identified as ubiquitous components of innate immune system and widely regarded as a potential source of future antibiotics owing to a remarkable set of advantageous properties ranging from broad spectrum of activity to low propensity of resistance development. However, AMPs present several drawbacks that strongly limit their clinical applicability as ideal drug candidates such as; poor bioavailability, potential immunogenicity and high production cost. Thus, to overcome the limitations of native peptides, peptidomimetic becomes an important and promising approach. The different research groups worldwide engaged in antimicrobial drug discovery over the past decade have paid tremendous effort to design peptidomimetics. This review will focus on recent approaches in design of antimicrobial peptidomimetics their structure-activity relationship studies, mode of action, selectivity & toxicity.

Antioxidant and antimicrobial properties of traditional green and purple "Napoletano" basil cultivars (Ocimum basilicum L.) from Campania region (Italy).

PubMed

Tenore, Gian Carlo; Campiglia, Pietro; Ciampaglia, Roberto; Izzo, Luana; Novellino, Ettore

2017-09-01

The present study is the first effort to a comprehensive evaluation of the antioxidant and antimicrobial activities of 'Napoletano' green and purple basil (Ocimum basilicum L.) varieties. The results obtained revealed that the basil sample extracts were characterised by a generally higher polyphenolic concentration than those reported elsewhere for other more conventional and geographically different basil varieties. Napoletano purple basil revealed higher radical-scavenging and ferric-reducing capacities than the green one probably due to its relevant anthocyanin content. As regards the antimicrobial properties, both basil varieties exhibited activity against a broad spectrum of food-borne and human pathogenic micro-organisms, revealing not only a moderate to high natural preserving capacity, but also potentially beneficial influence on human health. Results indicated Napoletano green and purple basils as a good source of antioxidants of potential nutraceutical interest.

Occidiofungin is an important component responsible for the antifungal activity of Burkholderia pyrrocinia strain Lyc2.

PubMed

Wang, X Q; Liu, A X; Guerrero, A; Liu, J; Yu, X Q; Deng, P; Ma, L; Baird, S M; Smith, L; Li, X D; Lu, S E

2016-03-01

To identify the taxonomy of tobacco rhizosphere-isolated strain Lyc2 and investigate the mechanisms of the antifungal activities, focusing on antimicrobials gene clusters identification and function analysis. Multilocus sequence typing and 16S rRNA analyses indicated that strain Lyc2 belongs to Burkholderia pyrrocinia. Bioassay results indicated strain Lyc2 showed significant antifungal activities against a broad range of plant and animal fungal pathogens and control efficacy on seedling damping off disease of cotton. A 55·2-kb gene cluster which was homologous to ocf gene clusters in Burkholderia contaminans MS14 was confirmed to be responsible for antifungal activities by random mutagenesis; HPLC was used to verify the production of antifungal compounds. Multiple antibiotic and secondary metabolized biosynthesis gene clusters predicated by antiSMASH revealed the broad spectrum of antimicrobials activities of the strain. Our results revealed the mechanisms of antifungal activities of strain Lyc2 and expand our knowledge about production of occidiofungin in the bacteria Burkholderia. Understanding the mechanisms of antifungal activities of strain Lyc2 has contributed to discovery of new antibiotics and expand our knowledge of production of occidiofungin in the bacteria Burkholderia. © 2015 The Society for Applied Microbiology.

Phytotherapy as an alternative to conventional antimicrobials: combating microbial resistance.

PubMed

Enioutina, Elena Yu; Teng, Lida; Fateeva, Tatyana V; Brown, Jessica C S; Job, Kathleen M; Bortnikova, Valentina V; Krepkova, Lubov V; Gubarev, Michael I; Sherwin, Catherine M T

2017-11-01

In the modern antimicrobial era, the rapid spread of resistance to antibiotics and introduction of new and mutating viruses is a global concern. Combating antimicrobial resistant microbes (AMR) requires coordinated international efforts that incorporate new conventional antibiotic development as well as development of alternative drugs with antimicrobial activity, management of existing antimicrobials, and rapid detection of AMR pathogens. Areas covered: This manuscript discusses some conventional strategies to control microbial resistance. The main purpose of the manuscript is to present information on specific herbal medicines that may serve as good treatment alternatives to conventional antimicrobials for infections sensitive to conventional as well as resistant strains of microorganisms. Expert commentary: Identification of potential new antimicrobials is challenging; however, one source for potential structurally diverse and complex antimicrobials are natural products. Natural products may have advantages over other post-germ theory antimicrobials. Many antimicrobial herbal medicines possess simultaneous antibacterial, antifungal, antiprotozoal and/or antiviral properties. Herbal products have the potential to boost host resistance to infections, particularly in immunocompromised patients. Antimicrobial broad-spectrum activity in conjunction with immunostimulatory properties may help to prevent microbial resistance to herbal medicine. As part of the efforts to broaden use of herbal medicines to treat microbial infections, pre-clinical and clinical testing guidelines of these compounds as a whole should be implemented to ensure consistency in formulation, efficacy and safety.

In Vivo, In Vitro, and In Silico Characterization of Peptoids as Antimicrobial Agents

PubMed Central

Fjell, Christopher D.; Waldbrook, Matt; Chongsiriwatana, Nathaniel P.; Yuen, Eddie; Hancock, Robert E. W.; Barron, Annelise E.

2016-01-01

Bacterial resistance to conventional antibiotics is a global threat that has spurred the development of antimicrobial peptides (AMPs) and their mimetics as novel anti-infective agents. While the bioavailability of AMPs is often reduced due to protease activity, the non-natural structure of AMP mimetics renders them robust to proteolytic degradation, thus offering a distinct advantage for their clinical application. We explore the therapeutic potential of N-substituted glycines, or peptoids, as AMP mimics using a multi-faceted approach that includes in silico, in vitro, and in vivo techniques. We report a new QSAR model that we developed based on 27 diverse peptoid sequences, which accurately correlates antimicrobial peptoid structure with antimicrobial activity. We have identified a number of peptoids that have potent, broad-spectrum in vitro activity against multi-drug resistant bacterial strains. Lastly, using a murine model of invasive S. aureus infection, we demonstrate that one of the best candidate peptoids at 4 mg/kg significantly reduces with a two-log order the bacterial counts compared with saline-treated controls. Taken together, our results demonstrate the promising therapeutic potential of peptoids as antimicrobial agents. PMID:26849681

Antimicrobial efficacy of 0·05% cetylpyridinium chloride mouthrinses.

PubMed

Sreenivasan, P K; Haraszthy, V I; Zambon, J J

2013-01-01

This study evaluated the antimicrobial activity of two commercially available 0·05% cetylpyridinium chloride (CPC) mouthrinses with or without alcohol and examined its antimicrobial activity on oral bacterial species including fresh clinical isolates compared to a chlorhexidine mouthrinse and a control fluoride mouthrinse without CPC. Two different approaches were used to evaluate antimicrobial activity. First, the minimum inhibitory concentration (MIC) was determined for each mouthrinse against a panel of 25 micro-organisms including species associated with dental caries, gingivitis and periodontitis. Second, supragingival dental plaque obtained from 15 adults was incubated with the four mouthrinses to evaluate antimicrobial activity on micro-organisms in oral biofilms. Both CPC mouthrinses exhibited lower MIC's, that is, greater antimicrobial activity, against oral Gram-negative bacteria especially periodontal pathogens and species implicated in halitosis such as Aggregatibacter actinomycemcomitans, Campylobacter rectus, Eikenella corrodens, Porphyromonas gingivalis, Prevotella intermedia and Solobacterium moorei than the control mouthrinse. Ex-vivo tests on supragingival plaque micro-organisms demonstrated significantly greater antimicrobial activity by the CPC mouthrinses (>90% killing, P < 0·001) and the chlorhexidine rinse (>98% killing, P < 0·05) compared to the control fluoride mouthrinse. Whilst the chlorhexidine mouthrinse was most effective, mouthrinses containing 0·05% CPC formulated with or without alcohol demonstrated broad-spectrum antimicrobial activity against both laboratory strains and supragingival plaque bacteria compared to a control mouthrinse without CPC. These in vitro and ex-vivo studies provide a biological rationale for previous clinical studies demonstrating the efficacy of CPC mouthrinses in reducing supragingival plaque and plaque-associated gingivitis. © 2012 The Society for Applied Microbiology.

Peptidomic approach identifies cruzioseptins, a new family of potent antimicrobial peptides in the splendid leaf frog, Cruziohyla calcarifer.

PubMed

Proaño-Bolaños, Carolina; Zhou, Mei; Wang, Lei; Coloma, Luis A; Chen, Tianbao; Shaw, Chris

2016-09-02

Phyllomedusine frogs are an extraordinary source of biologically active peptides. At least 8 families of antimicrobial peptides have been reported in this frog clade, the dermaseptins being the most diverse. By a peptidomic approach, integrating molecular cloning, Edman degradation sequencing and tandem mass spectrometry, a new family of antimicrobial peptides has been identified in Cruziohyla calcarifer. These 15 novel antimicrobial peptides of 20-32 residues in length are named cruzioseptins. They are characterized by having a unique shared N-terminal sequence GFLD- and the sequence motifs -VALGAVSK- or -GKAAL(N/G/S) (V/A)V- in the middle of the peptide. Cruzioseptins have a broad spectrum of antimicrobial activity and low haemolytic effect. The most potent cruzioseptin was CZS-1 that had a MIC of 3.77μM against the Gram positive bacterium, Staphylococcus aureus and the yeast Candida albicans. In contrast, CZS-1 was 3-fold less potent against the Gram negative bacterium, Escherichia coli (MIC 15.11μM). CZS-1 reached 100% haemolysis at 120.87μM. Skin secretions from unexplored species such as C. calcarifer continue to demonstrate the enormous molecular diversity hidden in the amphibian skin. Some of these novel peptides may provide lead structures for the development of a new class of antibiotics and antifungals of therapeutic use. Through the combination of molecular cloning, Edman degradation sequencing, tandem mass spectrometry and MALDI-TOF MS we have identified a new family of 15 antimicrobial peptides in the skin secretion of Cruziohyla calcarifer. The novel family is named "Cruzioseptins" and contains cationic amphipathic peptides of 20-32 residues. They have a broad range of antimicrobial activity that also includes effective antifungals with low haemolytic activity. Therefore, C. calcarifer has proven to be a rich source of novel peptides, which could become leading structures for the development of novel antibiotics and antifungals of clinical application. Copyright © 2016 Elsevier B.V. All rights reserved.

Lactolisterin BU, a Novel Class II Broad-Spectrum Bacteriocin from Lactococcus lactis subsp. lactis bv. diacetylactis BGBU1-4.

PubMed

Lozo, Jelena; Mirkovic, Nemanja; O'Connor, Paula M; Malesevic, Milka; Miljkovic, Marija; Polovic, Natalija; Jovcic, Branko; Cotter, Paul D; Kojic, Milan

2017-11-01

Lactococcus lactis subsp. lactis bv. diacetylactis BGBU1-4 produces a novel bacteriocin, lactolisterin BU, with strong antimicrobial activity against many species of Gram-positive bacteria, including important food spoilage and foodborne pathogens, such as Listeria monocytogenes , Staphylococcus aureus , Bacillus spp., and streptococci. Lactolisterin BU was extracted from the cell surface of BGBU1-4 by 2-propanol and purified to homogeneity by C 18 solid-phase extraction and reversed-phase high-performance liquid chromatography. The molecular mass of the purified lactolisterin BU was 5,160.94 Da, and an internal fragment, AVSWAWQH, as determined by N-terminal sequencing, showed low-level similarity to existing antimicrobial peptides. Curing and transformation experiments revealed the presence of a corresponding bacteriocin operon on the smallest plasmid, pBU6 (6.2 kb), of strain BGBU1-4. Analysis of the bacteriocin operon revealed a leaderless bacteriocin of 43 amino acids that exhibited similarity to bacteriocin BHT-B (63%) from Streptococcus ratti , a bacteriocin with analogy to aureocin A. IMPORTANCE Lactolisterin BU, a broad-spectrum leaderless bacteriocin produced by L. lactis subsp. lactis bv. diacetylactis BGBU1-4, expresses strong antimicrobial activity against food spoilage and foodborne pathogens, such as Listeria monocytogenes , Staphylococcus aureus , Bacillus spp., and streptococci. Lactolisterin BU showed the highest similarity to aureocin-like bacteriocins produced by different bacteria. The operon for synthesis is located on the smallest plasmid, pBU6 (6.2 kb), of strain BGBU1-4, indicating possible horizontal transfer among producers. Copyright © 2017 American Society for Microbiology.

Lactolisterin BU, a Novel Class II Broad-Spectrum Bacteriocin from Lactococcus lactis subsp. lactis bv. diacetylactis BGBU1-4

PubMed Central

Lozo, Jelena; Mirkovic, Nemanja; O'Connor, Paula M.; Malesevic, Milka; Miljkovic, Marija; Polovic, Natalija; Cotter, Paul D.

2017-01-01

ABSTRACT Lactococcus lactis subsp. lactis bv. diacetylactis BGBU1-4 produces a novel bacteriocin, lactolisterin BU, with strong antimicrobial activity against many species of Gram-positive bacteria, including important food spoilage and foodborne pathogens, such as Listeria monocytogenes, Staphylococcus aureus, Bacillus spp., and streptococci. Lactolisterin BU was extracted from the cell surface of BGBU1-4 by 2-propanol and purified to homogeneity by C18 solid-phase extraction and reversed-phase high-performance liquid chromatography. The molecular mass of the purified lactolisterin BU was 5,160.94 Da, and an internal fragment, AVSWAWQH, as determined by N-terminal sequencing, showed low-level similarity to existing antimicrobial peptides. Curing and transformation experiments revealed the presence of a corresponding bacteriocin operon on the smallest plasmid, pBU6 (6.2 kb), of strain BGBU1-4. Analysis of the bacteriocin operon revealed a leaderless bacteriocin of 43 amino acids that exhibited similarity to bacteriocin BHT-B (63%) from Streptococcus ratti, a bacteriocin with analogy to aureocin A. IMPORTANCE Lactolisterin BU, a broad-spectrum leaderless bacteriocin produced by L. lactis subsp. lactis bv. diacetylactis BGBU1-4, expresses strong antimicrobial activity against food spoilage and foodborne pathogens, such as Listeria monocytogenes, Staphylococcus aureus, Bacillus spp., and streptococci. Lactolisterin BU showed the highest similarity to aureocin-like bacteriocins produced by different bacteria. The operon for synthesis is located on the smallest plasmid, pBU6 (6.2 kb), of strain BGBU1-4, indicating possible horizontal transfer among producers. PMID:28842543

Appropriateness of gram-negative agent use at a tertiary care hospital in the setting of significant antimicrobial resistance.

PubMed

Vora, Neil M; Kubin, Christine J; Furuya, E Yoko

2015-01-01

Background.  Practicing antimicrobial stewardship in the setting of widespread antimicrobial resistance among gram-negative bacilli, particularly in urban areas, is challenging. Methods.  We conducted a retrospective cross-sectional study at a tertiary care hospital with an established antimicrobial stewardship program in New York, New York to determine appropriateness of use of gram-negative antimicrobials and to identify factors associated with suboptimal antimicrobial use. Adult inpatients who received gram-negative agents on 2 dates, 1 June 2010 or 1 December 2010, were identified through pharmacy records. Clinical data were collected for each patient. Use of gram-negative agents was deemed optimal or suboptimal through chart review and according to hospital guidelines. Data were compared using χ(2) or Fischer's exact test for categorical variables and Student t test or Mann-Whitney U test for continuous variables. Results.  A total of 356 patients were included who received 422 gram-negative agents. Administration was deemed suboptimal in 26% of instances, with the most common reason being spectrum of activity too broad. In multivariable analysis, being in an intensive care unit (adjusted odds ratio [aOR], .49; 95% confidence interval [CI], .29-.84), having an infectious diseases consultation within the previous 7 days (aOR, .52; 95% CI, .28-.98), and having a history of multidrug-resistant gram-negative bacilli within the past year (aOR, .24; 95% CI, .09-.65) were associated with optimal gram-negative agent use. Beta-lactam/beta-lactamase inhibitor combination drug use (aOR, 2.6; 95% CI, 1.35-5.16) was associated with suboptimal use. Conclusions.  Gram-negative agents were used too broadly despite numerous antimicrobial stewardship program activities.

Structure-Activity Relationship of Benzophenanthridine Alkaloids from Zanthoxylum rhoifolium Having Antimicrobial Activity

PubMed Central

Tavares, Luciana de C.; Zanon, Graciane; Weber, Andréia D.; Neto, Alexandre T.; Mostardeiro, Clarice P.; Da Cruz, Ivana B. M.; Oliveira, Raul M.; Ilha, Vinicius; Dalcol, Ionara I.; Morel, Ademir F.

2014-01-01

Zanthoxylum rhoifolium (Rutaceae) is a plant alkaloid that grows in South America and has been used in Brazilian traditional medicine for the treatment of different health problems. The present study was designed to evaluate the antimicrobial activity of the steam bark crude methanol extract, fractions, and pure alkaloids of Z. rhoifolium. Its stem bark extracts exhibited a broad spectrum of antimicrobial activity, ranging from 12.5 to 100 µg/mL using bioautography method, and from 125 to 500 µg/mL in the microdilution bioassay. From the dichloromethane basic fraction, three furoquinoline alkaloids (1–3), and nine benzophenanthridine alkaloids (4–12) were isolated and the antimicrobial activity of the benzophenanthridine alkaloids is discussed in terms of structure-activity relationships. The alkaloid with the widest spectrum of activity was chelerythrine (10), followed by avicine (12) and dihydrochelerythrine (4). The minimal inhibitory concentrations of chelerythrine, of 1.50 µg/mL for all bacteria tested, and between 3.12 and 6.25 µg/mL for the yeast tested, show this compound to be a more powerful antimicrobial agent when compared with the other active alkaloids isolated from Z. rhoifolium. To verify the potential importance of the methylenedioxy group (ring A) of these alkaloids, chelerythrine was selected to represent the remainder of the benzophenanthridine alkaloids isolated in this work and was subjected to a demethylation reaction giving derivative 14. Compared to chelerythrine, the derivative (14) was less active against the tested bacteria and fungi. Kinetic measurements of the bacteriolytic activities of chelerythrine against the bacteria Bacillus subtilis (Gram-positive) and Escherichia coli (Gram-negative) were determined by optical density based on real time assay, suggesting that its mechanism of action is not bacteriolytic. The present study did not detect hemolytic effects of chelerythrine on erythrocytes and found a protective effect considering the decrease in TBARS and AOPP (advanced oxidized protein products) levels when compared to the control group. PMID:24824737

Antimicrobial Peptides as Potential Alternatives to Antibiotics in Food Animal Industry.

PubMed

Wang, Shuai; Zeng, Xiangfang; Yang, Qing; Qiao, Shiyan

2016-05-03

Over the last decade, the rapid emergence of multidrug-resistant pathogens has become a global concern, which has prompted the search for alternative antibacterial agents for use in food animals. Antimicrobial peptides (AMPs), produced by bacteria, insects, amphibians and mammals, as well as by chemical synthesis, are possible candidates for the design of new antimicrobial agents because of their natural antimicrobial properties and a low propensity for development of resistance by microorganisms. This manuscript reviews the current knowledge of the basic biology of AMPs and their applications in non-ruminant nutrition. Antimicrobial peptides not only have broad-spectrum activity against bacteria, fungi, and viruses but also have the ability to bypass the common resistance mechanisms that are placing standard antibiotics in jeopardy. In addition, AMPs have beneficial effects on growth performance, nutrient digestibility, intestinal morphology and gut microbiota in pigs and broilers. Therefore, AMPs have good potential as suitable alternatives to conventional antibiotics used in swine and poultry industries.

Helical Antimicrobial Sulfono- {gamma} -AApeptides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yaqiong; Wu, Haifan; Teng, Peng

Host-defense peptides (HDPs) such as magainin 2 have emerged as potential therapeutic agents combating antibiotic resistance. Inspired by their structures and mechanism of action, herein we report the fi rst example of antimicrobial helical sulfono- γ - AApeptide foldamers. The lead molecule displays broad-spectrum and potent antimicrobial activity against multi-drug-resistant Gram- positive and Gram-negative bacterial pathogens. Time-kill studies and fl uorescence microscopy suggest that sulfono- γ -AApeptides eradicate bacteria by taking a mode of action analogous to that of HDPs. Clear structure - function relationships exist in the studied sequences. Longer sequences, presumably adopting more-de fi ned helical structures, aremore » more potent than shorter ones. Interestingly, the sequence with less helical propensity in solution could be more selective than the stronger helix-forming sequences. Moreover, this class of antimicrobial agents are resistant to proteolytic degradation. These results may lead to the development of a new class of antimicrobial foldamers combating emerging antibiotic-resistant pathogens.« less

Advances in Development of Antimicrobial Peptidomimetics as Potential Drugs.

PubMed

Molchanova, Natalia; Hansen, Paul R; Franzyk, Henrik

2017-08-29

The rapid emergence of multidrug-resistant pathogens has evolved into a global health problem as current treatment options are failing for infections caused by pan-resistant bacteria. Hence, novel antibiotics are in high demand, and for this reason antimicrobial peptides (AMPs) have attracted considerable interest, since they often show broad-spectrum activity, fast killing and high cell selectivity. However, the therapeutic potential of natural AMPs is limited by their short plasma half-life. Antimicrobial peptidomimetics mimic the structure and biological activity of AMPs, but display extended stability in the presence of biological matrices. In the present review, focus is on the developments reported in the last decade with respect to their design, synthesis, antimicrobial activity, cytotoxic side effects as well as their potential applications as anti-infective agents. Specifically, only peptidomimetics with a modular structure of residues connected via amide linkages will be discussed. These comprise the classes of α-peptoids ( N -alkylated glycine oligomers), β-peptoids ( N -alkylated β-alanine oligomers), β³-peptides, α/β³-peptides, α-peptide/β-peptoid hybrids, α/γ N -acylated N -aminoethylpeptides (AApeptides), and oligoacyllysines (OAKs). Such peptidomimetics are of particular interest due to their potent antimicrobial activity, versatile design, and convenient optimization via assembly by standard solid-phase procedures.

A heterodimer comprised of two bovine lactoferrin antimicrobial peptides exhibits powerful bactericidal activity against Burkholderia pseudomallei.

PubMed

Puknun, Aekkalak; Bolscher, Jan G M; Nazmi, Kamran; Veerman, Enno C I; Tungpradabkul, Sumalee; Wongratanacheewin, Surasakdi; Kanthawong, Sakawrat; Taweechaisupapong, Suwimol

2013-07-01

Melioidosis is a severe infectious disease that is endemic in Southeast Asia and Northern Australia. Burkholderia pseudomallei, the causative agent of this disease, has developed resistance to an increasing list of antibiotics, demanding a search for novel agents. Lactoferricin and lactoferrampin are two antimicrobial domains of lactoferrin with a broad spectrum of antimicrobial activity. A hybrid peptide (LFchimera) containing lactoferrampin (LFampin265-284) and a part of lactoferricin (LFcin17-30) has strikingly higher antimicrobial activities compared to the individual peptides. In this study, the antimicrobial activities of this chimeric construct (LFchimera1), as well as of another one containing LFcin17-30 and LFampin268-284, a shorter fragment of LFampin265-284 (LFchimera2), and the constituent peptides were tested against 7 isolates of B. pseudomallei and compared to the preferential antibiotic ceftazidime (CAZ). All isolates including B. pseudomallei 979b shown to be resistant to CAZ, at a density of 10(5) CFU/ml, could be killed by 5-10 μM of LFchimera1 within 2 h, while the other peptides as well as the antibiotic CAZ only inhibited the B. pseudomallei strains resulting in an overgrowth in 24 h. These data indicate that LFchimera1 could be considered for development of therapeutic agents against B. pseudomallei.

Antimicrobial and Immunomodulatory Activities of PR-39 Derived Peptides

PubMed Central

Veldhuizen, Edwin J. A.; Schneider, Viktoria A. F.; Agustiandari, Herfita; van Dijk, Albert; Tjeerdsma-van Bokhoven, Johanna L. M.; Bikker, Floris J.; Haagsman, Henk P.

2014-01-01

The porcine cathelicidin PR-39 is a host defence peptide that plays a pivotal role in the innate immune defence of the pig against infections. Besides direct antimicrobial activity, it is involved in immunomodulation, wound healing and several other biological processes. In this study, the antimicrobial- and immunomodulatory activity of PR-39, and N- and C-terminal derivatives of PR-39 were tested. PR-39 exhibited an unexpected broad antimicrobial spectrum including several Gram positive strains such as Bacillus globigii and Enterococcus faecalis. Of organisms tested, only Staphylococcus aureus was insensitive to PR-39. Truncation of PR-39 down to 15 (N-terminal) amino acids did not lead to major loss of activity, while peptides corresponding to the C-terminal part of PR-39 were hampered in their antimicrobial activity. However, shorter peptides were all much more sensitive to inhibition by salt. Active peptides induced ATP leakage and loss of membrane potential in Bacillus globigii and Escherichia coli, indicating a lytic mechanism of action for these peptides. Finally, only the mature peptide was able to induce IL-8 production in porcine macrophages, but some shorter peptides also had an effect on TNF-α production showing differential regulation of cytokine induction by PR-39 derived peptides. None of the active peptides showed high cytotoxicity highlighting the potential of these peptides for use as an alternative to antibiotics. PMID:24755622

Antimicrobial synergism and cytotoxic properties of Citrus limon L., Piper nigrum L. and Melaleuca alternifolia (Maiden and Betche) Cheel essential oils.

PubMed

Nikolić, Miloš M; Jovanović, Katarina K; Marković, Tatjana Lj; Marković, Dejan Lj; Gligorijević, Nevenka N; Radulović, Siniša S; Kostić, Marina; Glamočlija, Jasmina M; Soković, Marina D

2017-11-01

The chemical composition, antimicrobial and synergistic effect, and cytotoxic activity of Citrus limon (lemon), Piper nigrum (green pepper) and Melaleuca alternifoila (tea tree) essential oils (EOs) were investigated. Chemical analyses of essential oils were tested by GC-FID and GC-MS spectroscopy. The antimicrobial activity assay was conducted using microdilution method against several oral bacteria and Candida spp. originating from the humans with oral disorders. The synergistic antimicrobial activity was evaluated using checkerboard method. The cytotoxicity evaluation of EOs was assessed using MTT test. Limonene (37.5%) and β-pinene (17.9%) were the major compounds in C. limon oil, β-pinene (34.4%), δ-3-carene (19.7%), limonene (18.7%) and α-pinene (10.4%) in P. nigrum oil and terpinen-4-ol (38.6%) and γ-terpinene (21.7%) in M. alternifolia oil. The broad-spectrum antimicrobial activity was achieved by tested three EOs, with C. limon oil being the strongest against bacteria and M. alternifolia oil strongest against fungi. The EOs demonstrated synergism; their combined application revealed an increase in antimicrobial activity. All tested essential oils showed lower cytotoxic activity in comparison with the positive control, and the obtained results confirmed a dose-dependent activity. The results of this study encourage use of tested EOs in development of a novel agent intended for prevention or therapy of corresponding oral disorders. © 2017 Royal Pharmaceutical Society.

Activity of LL-37, CRAMP and antimicrobial peptide-derived compounds E2, E6 and CP26 against Mycobacterium tuberculosis.

PubMed

Rivas-Santiago, Bruno; Rivas Santiago, Cesar E; Castañeda-Delgado, Julio E; León-Contreras, Juan C; Hancock, Robert E W; Hernandez-Pando, Rogelio

2013-02-01

Tuberculosis (TB) is a major worldwide health problem in part due to the lack of development of new treatments and the emergence of new strains such as multidrug-resistant (MDR) and extensively drug-resistant strains that are threatening and impairing the control of this disease. In this study, the efficacy of natural and synthetic cationic antimicrobial (host defence) peptides that have been shown often to possess broad-spectrum antimicrobial activity was tested. The natural antimicrobial peptides human LL-37 and mouse CRAMP as well as synthetic peptides E2, E6 and CP26 were tested for their activity against Mycobacterium tuberculosis both in in vitro and in vivo models. The peptides had moderate antimicrobial activities, with minimum inhibitory concentrations ranging from 2 μg/mL to 10 μg/mL. In a virulent model of M. tuberculosis lung infection, intratracheal therapeutic application of these peptides three times a week at doses of ca. 1mg/kg led to significant 3-10-fold reductions in lung bacilli after 28-30 days of treatment. The treatments worked both against the drug-sensitive H37Rv strain and a MDR strain. These results indicate that antimicrobial peptides might constitute a novel therapy against TB. Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

An amino acid composition criterion for membrane active antimicrobials

NASA Astrophysics Data System (ADS)

Schmidt, Nathan; Lai, Ghee Hwee; Mishra, Abhijit; Bong, Dennis; McCray, Paul, Jr.; Selsted, Michael; Ouellette, Andre; Wong, Gerard

2011-03-01

Membrane active antimicrobials (AMPs) are short amphipathic peptides with broad spectrum anti microbial activity. While it is believed that their hydrophobic and cationic moieties are responsible for membrane-based mechanisms of action, membrane disruption by AMPs is manifested in a diversity of outcomes, such as pore formation, blebbing, and budding. This complication, along with others, have made a detailed, molecular understanding of AMPs difficult. We use synchrotron small angle xray scattering to investigate the interaction of model bacterial and eukaryotic cell membranes with archetypes from beta-sheet AMPs (e.g. defensins) and alpha-helical AMPs (e.g. magainins). The relationship between membrane composition and peptide induced changes in membrane curvature and topology is examined. By comparing the membrane rearrangement and phase behavior induced by these different peptides we will discuss the importance of amino acid composition on AMP design.

Synergistic antimicrobial activity of Boswellia serrata Roxb. ex Colebr. (Burseraceae) essential oil with various azoles against pathogens associated with skin, scalp and nail infections.

PubMed

Sadhasivam, S; Palanivel, S; Ghosh, S

2016-12-01

Antimicrobials from natural sources have gained immense importance in recent times to combat the global challenge of antibiotic resistance. Essential oils are implicated in antimicrobial action against several species. Here, we have screened nine commercially available essential oils for their antimicrobial activity against organisms associated with skin, scalp and nail infections mainly Propionibacterium acnes, Malassezia spp., Candida albicans and Trichophyton spp. Among nine essential oils, Boswellia serrata essential oil demonstrated superior antimicrobial activity against all the micro-organisms and surprisingly it showed maximum activity against Trichophyton spp. The gas chromatography-mass spectrometry analysis of B. serrata oil indicates a major composition of α thujene, ρ cymene and sabinene. Additionally, B. serrata oil was found to inhibit Staphylococcus epidermidis biofilm, and its combination with azoles has shown synergistic activity against azole-resistant strain of C. albicans. These broad-spectrum antimicrobial activities of B. serrata oil will make it an ideal candidate for topical use. Eradication of skin and nail infections still remain a challenge and there are serious concerns regarding the recurrence of the diseases associated with these infections. Antimicrobials from plant sources are gaining importance in therapeutics because they encounter minimal challenges of emergence of resistance. We have demonstrated the antimicrobial activity of Boswellia serrata essential oil against micro-organisms involved in skin, scalp and nail infections, especially if it has shown favourable synergistic antifungal activity in combination with azoles against the azole-resistant Candida albicans strain. Thus, B. serrata oil can be one of the plausible therapeutic agents for management of skin, scalp and nail infections. © 2016 The Society for Applied Microbiology.

Pituitary adenylate cyclase-activating polypeptide is a potent broad-spectrum antimicrobial peptide: Structure-activity relationships.

PubMed

Starr, Charles G; Maderdrut, Jerome L; He, Jing; Coy, David H; Wimley, William C

2018-06-01

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a naturally occurring cationic peptide with potent immunosuppressant and cytoprotective activities. We now show that full length PACAP38 and to a lesser extent, the truncated form PACAP27, and the closely related vasoactive intestinal peptide (VIP) and secretin had antimicrobial activity against the Gram-negative bacteria Escherichia coli in the radial diffusion assay. PACAP38 was more potent than either the bovine neutrophil antimicrobial peptide indolicidin or the synthetic antimicrobial peptide ARVA against E. coli. PACAP38 also had activity against the Gram-positive bacteria Staphylococcus aureus in the same assay with comparable potency to indolicidin and ARVA. In the more stringent broth dilution assay, PACAP38 had moderate sterilizing activity against E. coli, and potent sterilizing activity against the Gram-negative bacteria Pseudomonas aeruginosa. PACAP27, VIP and secretin were much less active than PACAP38 in this assay. PACAP38 also had some activity against the Gram-positive bacteria Bacillus cereus in the broth dilution assay. Many exopeptidase-resistant analogs of PACAP38, including both receptor agonists and antagonists, had antimicrobial activities equal to, or better than PACAP38, in both assays. PACAP38 made the membranes of E. coli permeable to SYTOX Green, suggesting a classical membrane lytic mechanism. These data suggest that analogs of PACPAP38 with a wide range of useful biological activities can be made by judicious substitutions in the sequence. Copyright © 2018 Elsevier Inc. All rights reserved.

Design of Embedded-Hybrid Antimicrobial Peptides with Enhanced Cell Selectivity and Anti-Biofilm Activity

PubMed Central

Xu, Wei; Zhu, Xin; Tan, Tingting; Li, Weizhong; Shan, Anshan

2014-01-01

Antimicrobial peptides have attracted considerable attention because of their broad-spectrum antimicrobial activity and their low prognostic to induce antibiotic resistance which is the most common source of failure in bacterial infection treatment along with biofilms. The method to design hybrid peptide integrating different functional domains of peptides has many advantages. In this study, we designed an embedded-hybrid peptide R-FV-I16 by replacing a functional defective sequence RR7 with the anti-biofilm sequence FV7 embedded in the middle position of peptide RI16. The results demonstrated that the synthetic hybrid the peptide R-FV-I16 had potent antimicrobial activity over a wide range of Gram-negative and Gram-positive bacteria, as well as anti-biofilm activity. More importantly, R-FV-I16 showed lower hemolytic activity and cytotoxicity. Fluorescent assays demonstrated that R-FV-I16 depolarized the outer and the inner bacterial membranes, while scanning electron microscopy and transmission electron microscopy further indicated that this peptide killed bacterial cells by disrupting the cell membrane, thereby damaging membrane integrity. Results from SEM also provided evidence that R-FV-I16 inherited anti-biofilm activity from the functional peptide sequence FV7. Embedded-hybrid peptides could provide a new pattern for combining different functional domains and showing an effective avenue to screen for novel antimicrobial agents. PMID:24945359

Evaluation of some pharmacological activities of Budmunchiamine - A isolated from Albizia amara.

PubMed

Thippeswamy, Sreerangegowda; Mohana, Devihalli Chikkaiah; Abhishek, Rayasandra Umesh; Manjunath, Kiragandur

2015-03-01

The present investigations were aimed to evaluate the antimicrobial and antioxidant efficacies of budmunchiamine-A (BUA) of Albizia amara . The activity-guided isolation leaded to isolate the bioactive compound budmunchiamine-A from alkaloid extract of A. amara . The budmunchiamine-A showed significant broad-spectrum antimicrobial activity with zone of inhibition (ZOI), minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC) values varied from 7.3 to 24.5 mm, 0.95 to 62.5 μg/mL, and 1.9 to 250 μg/mL, respectively. The budmunchiamine-A exhibited moderate antioxidant activity with inhibitory concentration 50% (IC 50 ) value of 400 μg/mL in 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and percent inhibition of β-carotene/linoleic acid was 67.8%. The results suggest the possible use of budmunchiamine-A as a molecular entity for drug development in pharmaceutical industry.

Evaluation of some pharmacological activities of Budmunchiamine - A isolated from Albizia amara

PubMed Central

Thippeswamy, Sreerangegowda; Mohana, Devihalli Chikkaiah; Abhishek, Rayasandra Umesh; Manjunath, Kiragandur

2015-01-01

The present investigations were aimed to evaluate the antimicrobial and antioxidant efficacies of budmunchiamine-A (BUA) of Albizia amara . The activity-guided isolation leaded to isolate the bioactive compound budmunchiamine-A from alkaloid extract of A. amara . The budmunchiamine-A showed significant broad-spectrum antimicrobial activity with zone of inhibition (ZOI), minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC) values varied from 7.3 to 24.5 mm, 0.95 to 62.5 μg/mL, and 1.9 to 250 μg/mL, respectively. The budmunchiamine-A exhibited moderate antioxidant activity with inhibitory concentration 50% (IC 50 ) value of 400 μg/mL in 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and percent inhibition of β-carotene/linoleic acid was 67.8%. The results suggest the possible use of budmunchiamine-A as a molecular entity for drug development in pharmaceutical industry. PMID:26221099

The Potential Use of Natural and Structural Analogues of Antimicrobial Peptides in the Fight against Neglected Tropical Diseases.

PubMed

Lewies, Angélique; Wentzel, Johannes F; Jacobs, Garmi; Du Plessis, Lissinda H; Angélique, Lewies; Frederik, Wentzel Johannes; Garmi, Jacobs; Hester, Du Plessis Lissinda

2015-08-24

Recently, research into the development of new antimicrobial agents has been driven by the increase in resistance to traditional antibiotics and Emerging Infectious Diseases. Antimicrobial peptides (AMPs) are promising candidates as alternatives to current antibiotics in the treatment and prevention of microbial infections. AMPs are produced by all known living species, displaying direct antimicrobial killing activity and playing an important role in innate immunity. To date, more than 2000 AMPs have been discovered and many of these exhibit broad-spectrum antibacterial, antiviral and anti-parasitic activity. Neglected tropical diseases (NTDs) are caused by a variety of pathogens and are particularly wide-spread in low-income and developing regions of the world. Alternative, cost effective treatments are desperately needed to effectively battle these medically diverse diseases. AMPs have been shown to be effective against a variety of NTDs, including African trypanosomes, leishmaniosis and Chagas disease, trachoma and leprosy. In this review, the potential of selected AMPs to successfully treat a variety of NTD infections will be critically evaluated.

Purification and characterization of bacteriocin produced by oral Lactobacillus paracasei SD1.

PubMed

Wannun, P; Piwat, S; Teanpaisan, R

2014-06-01

The present study aimed to purify and characterize the antimicrobial protein from Lactobacillus paracasei SD1, which is a strain from the human oral cavity. Antimicrobial activity was obtained from purifying the culture supernatant of L. paracasei SD1. Purification of the active compound was achieved with ammonium sulfate precipitation followed by chloroform and gel filtration chromatography. As revealed by SDS-PAGE, the active fraction was homogeneous, showing a protein with an approximate molecular weight of 25,000 Da. It was confirmed as having a molecular mass of 24,028.2 Da by mass spectrometry. The antimicrobial compound, named "paracasin SD1", exhibited a broad spectrum against oral pathogens. Paracasin SD1 was stable in a pH range between 3.0 and 8.0 at 100 °C for 5 min, and showed resistance to α-amylase, catalase, lysozyme and whole saliva. However, its activity was lost after proteinase K and trypsin treatment. The results obtained suggest the possibility of using paracasin SD1 for application in prevention/treatment of oral diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Accidental injection of sodium hypochlorite in inferior alveolar nerve block anesthesia].

PubMed

Hongyan, Li; Jian, Xu; Baorong, Zhang; Yue, Jia; Minhua, Liu; Yilang, Luo; Jing, Zhao

2016-12-01

Sodium hypochlorite (NaClO) has been widely used in clinical practice as one of the most efficient root canal irrigants. Its properties include broad-spectrum antimicrobial activity and ability to dissolve necrotic tissues. However, when used improperly, NaClO can cause a series of adverse reactions, such as mucosal inflammation, irritation, or injury. This paper presents a case of accidental injection of NaClO in inferior alveolar nerve block anesthesia.

Evaluation of Novel Antimicrobial Peptides as Topical Anti-Infectives with Broad-Spectrum Activity against Combat-Related Bacterial and Fungal Wound Infections

DTIC Science & Technology

2017-10-01

proceed with studies at Bridge PTS in Austin , TX . 6. Products Poster #1054 presentation at MHSRS 2016 First Prize Award 7. Participants and...Bioscience, Inc. REPORT DATE: October 2017 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort Detrick...Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 11. SPONSOR/MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION / AVAILABILITY

Antibiotic policies in acute English NHS trusts: implementation of 'Start Smart-Then Focus' and relationship with Clostridium difficile infection rates.

PubMed

Llewelyn, Martin J; Hand, Kieran; Hopkins, Susan; Walker, A Sarah

2015-04-01

The objective of this study was to establish how antibiotic prescribing policies at National Health Service (NHS) hospitals match the England Department of Health 'Start Smart-Then Focus' recommendations and relate to Clostridium difficile infection (CDI) rates. Antibiotic pharmacists were surveyed regarding recommendations for empirical treatment of common syndromes ('Start Smart') and antimicrobial prescription reviews ('Focus') at their hospital trusts. If no response was provided, policy data were sought from trust websites and the MicroGuide app (Horizon Strategic Partners, UK). Empirical treatment recommendations were categorized as broad spectrum (a β-lactam penicillin/β-lactamase inhibitor, cephalosporin, quinolone or carbapenem) or narrow spectrum. CDI rates were gathered from the national mandatory surveillance system. Data were obtained for 105/145 English acute hospital trusts (72%). β-Lactam/β-lactamase inhibitor combinations were recommended extensively. Only for severe community-acquired pneumonia and pyelonephritis were narrow-spectrum agents recommended first line at a substantial number of trusts [42/105 (40%) and 50/105 (48%), respectively]. Policies commonly recommended dual therapy with aminoglycosides and β-lactams for abdominal sepsis [40/93 trusts (43%)] and undifferentiated severe sepsis [54/94 trusts (57%)]. Most policies recommended treating for ≥ 7 days for most indications. Nearly all policies [100/105 trusts (95%)] recommended antimicrobial prescription reviews, but only 46/96 respondents (48%) reported monitoring compliance. Independent predictors of higher CDI rates were recommending a broad-spectrum regimen for community-acquired pneumonia (P=0.06) and, counterintuitively, a recommended treatment duration of <48 h for nosocomial pneumonia (P=0.01). Hospital antibiotic policies in the NHS 'Start Smart' by recommending broad-spectrum antibiotics for empirical therapy, but this may have the unintended potential to increase the use of broad-spectrum antibiotics and risk of CDI unless better mechanisms are in place to improve 'Focus'. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Impact of broad-spectrum antimicrobial treatment on the ecology of intestinal flora.

PubMed

Yang, Jen-Jia; Wang, Jann-Tay; Cheng, Aristine; Chuang, Yu-Chung; Sheng, Wang-Huei

2017-06-28

Suppression of intestinal flora by broad-spectrum antimicrobial agents facilitated risk of colonization or infection with resistant pathogen. We aimed to investigate the changes in bowel carriage of target resistant microorganisms (TRO) among patients treated with three different classes of Pseudomonas-sparing broad-spectrum antimicrobial agents (ertapenem, moxifloxacin and flomoxef) with anaerobic coverage. Risk factors for developing colonization of TRO were also analyzed. We prospectively enrolled the adult hospitalized patients (>20 years old) who were indicated for at least 7-day course with either of ertapenem, moxifloxacin or flomoxef. Rectal swabs were performed for the patients who received at least 1-day course of study antibiotics during the treatment duration. The TROs included Pseudomonas aeruginosa, Enterobacteriaceae, and Acinetobacter baumannii. MacConkey agars with study antibiotics were used to isolate the TROs and evaluate the antimicrobial resistance. The mean age of our study population was 61.6 years, and 58.8% were males. The rates of rectal colonization for Pseudomonas aeruginosa was similar among the study medications (ertapenem 13.2%, flomoxef 20%, moxifloxacin 14.3%, p = 0.809). Compared with ertapenem, flomoxef (odds ratio [OR], 4.30; 95% confidence interval [95% CI], 1.28-14.48, p = 0.019) and moxifloxacin (OR, 6.95; 95% CI, 1.36-35.52, p = 0.019) had higher risk for colonization of ertapenem-resistant Escherichiacoli colonization. The patients who received treatment of ertapenem may have a lower risk of rectal colonization for ertapenem resistant Escherichia coli than those who received flomoxef or moxifloxacin. The rate of Pseudomonas colonization did not differ between the three study Pseudomonas-sparing agents. Copyright © 2017. Published by Elsevier B.V.

CMC stabilized nano silver synthesis, characterization and its antibacterial and synergistic effect with broad spectrum antibiotics.

PubMed

Prema, P; Thangapandiyan, S; Immanuel, G

2017-02-20

In the present study silver nanoparticles were synthesized by reduction of AgNO 3 using aqueous CMC solution, which acts as both reducing and capping agent. The formation of AgNO 3 nanoparticles was observed visually by color change and these nanoparticles were characterized through UV-vis spectroscopy, FTIR, XRD, SEM, EDS and AFM. The FTIR peaks observed to be ranging from 3300 to 605cm -1 . The AFM image clearly showed the surface morphology of well dispersed nanoparticles. SEM image illustrates the nanoparticles with spherical shape. The crystalline nature of the particles was assured by XRD analysis. The antimicrobial activity of nanoparticles was tested against human bacterial pathogens (Bacillus cereus, Staphylococcus aureus, S. epidermidis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhimurium &Vibrio vulnificus). The bacterial growth was highly inhibited by the nanoparticles. The synergistic effect of nanoparticles in combination with selected broad spectrum antibiotics against the tested bacteria determined strong growth inhibitory activity. Copyright © 2016. Published by Elsevier Ltd.

Time series analysis of the impact of an intervention in Tayside, Scotland to reduce primary care broad-spectrum antimicrobial use.

PubMed

Hernandez-Santiago, Virginia; Marwick, Charis A; Patton, Andrea; Davey, Peter G; Donnan, Peter T; Guthrie, Bruce

2015-08-01

Concern about Clostridium difficile infection (CDI) and resistance has driven interventions internationally to reduce broad-spectrum antimicrobial use. An intervention combining guidelines, education and feedback was implemented in Tayside, Scotland in 2009 aiming to reduce primary care prescribing of co-amoxiclav, cephalosporins, fluoroquinolones and clindamycin ('4C antimicrobials'). Our aim was to assess the impact of this real-world intervention on antimicrobial prescribing rates. We used interrupted time series with segmented regression analysis to examine associations between the intervention and changes in antimicrobial prescribing (quarterly rates of patients exposed to 4C antimicrobials, non-4C antimicrobials and any antimicrobial in 2005-12). The intervention was associated with a highly significant and sustained decrease in 4C antimicrobial prescribing, by 33.5% (95% CI -26.1 to -40.9), 42.2% (95% CI -34.2 to -50.2) and 55.5% (95% CI -45.9 to -65.1) at 6, 12 and 24 months after intervention, respectively. The effect was seen across all age groups, with the largest reductions in people aged 65 years and over (58.4% reduction at 24 months, 95% CI -46.7 to -70.1) and care home residents (65.6% reduction at 24 months, 95% CI -51.8 to -79.4). There were balancing increases in doxycycline, nitrofurantoin and trimethoprim prescribing as well as a reduction in macrolide prescribing. Total antimicrobial exposure did not change. A real-world intervention to reduce primary care prescribing of antimicrobials associated with CDI led to large, sustained reductions in the targeted prescribing, largely due to substitution with guideline-recommended antimicrobials rather than by avoiding antimicrobial use altogether. Further research is needed to examine the impact on antimicrobial resistance. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The ABCs of the US Broad Spectrum Antimicrobials Program: Antibiotics, Biosecurity, and Congress

PubMed Central

2015-01-01

Antibiotic resistance has been increasing at an alarming rate in the United States and globally for decades, but the problem has only recently gained broad attention at the highest levels of the US government. More and more patients are dying of infections that do not respond to antibiotics that are currently available. Meanwhile, the antibacterial product pipeline remains fragile in part because of a lack of commercial interest from pharmaceutical companies. The Biomedical Advanced Research and Development Authority (BARDA) Broad Spectrum Antimicrobials (BSA) program leads the US government's effort to bridge this gap by advancing new antibacterials through late stages of clinical development. Other commentators have described in detail BARDA's structure, process, and role in antibacterial development. This commentary offers a public policy perspective on the emerging politics of antibiotic resistance in the context of US biosecurity politics and medical countermeasure (MCM) development. It identifies promising developments and difficult challenges that together will ultimately determine whether BARDA can become a global leader for antibiotic development. PMID:26569379

European Surveillance of Antimicrobial Consumption (ESAC): outpatient penicillin use in Europe.

PubMed

Ferech, Matus; Coenen, Samuel; Dvorakova, Katerina; Hendrickx, Erik; Suetens, Carl; Goossens, Herman

2006-08-01

Data on outpatient penicillin use in Europe were collected from 25 countries within the ESAC project, funded by DG SANCO of the European Commission, using the WHO ATC/DDD methodology. For the period 1997-2003, data on outpatient use of systemic penicillins aggregated at the level of the active substance were collected and expressed in DDD (WHO, version 2004) per 1000 inhabitants per day (DID). Of the 'Penicillins' (J01C), outpatient use of narrow-spectrum penicillins (J01CE), broad-spectrum penicillins (J01CA), penicillinase-resistant penicillins (J01CF) and combinations with beta-lactamase inhibitors (J01CR) in 25 European countries was analysed in detail. Total outpatient penicillin use in 2003 varied by a factor of 4 between the country with the highest (15.27 DID in Slovakia) and lowest use (3.86 DID in the Netherlands). Narrow-spectrum penicillins, broad-spectrum penicillins and combinations with beta-lactamase inhibitors were used most in 4, 12 and 9 countries, respectively. Penicillin use increased by more than 1 DID in nine countries, whereas it decreased by more than 1 DID in two countries (Czech Republic, France). An increase of the use of combinations with beta-lactamase inhibitors by more than 10% in 10 countries coincided with an equal decrease of broad-spectrum penicillins in seven countries and narrow-spectrum penicillins in three countries. Penicillins represent the most widely used antibiotic class in all 25 participating countries; albeit with considerable variation of their use patterns. A distinct shift from narrow-spectrum penicillins to broad-spectrum penicillins, and specifically their combinations with beta-lactamase inhibitors, was observed during the period 1997-2003.

Antimicrobial Peptides: Insights into Membrane Permeabilization, Lipopolysaccharide Fragmentation and Application in Plant Disease Control.

PubMed

Datta, Aritreyee; Ghosh, Anirban; Airoldi, Cristina; Sperandeo, Paola; Mroue, Kamal H; Jiménez-Barbero, Jesús; Kundu, Pallob; Ramamoorthy, Ayyalusamy; Bhunia, Anirban

2015-07-06

The recent increase in multidrug resistance against bacterial infections has become a major concern to human health and global food security. Synthetic antimicrobial peptides (AMPs) have recently received substantial attention as potential alternatives to conventional antibiotics because of their potent broad-spectrum antimicrobial activity. These peptides have also been implicated in plant disease control for replacing conventional treatment methods that are polluting and hazardous to the environment and to human health. Here, we report de novo design and antimicrobial studies of VG16, a 16-residue active fragment of Dengue virus fusion peptide. Our results reveal that VG16KRKP, a non-toxic and non-hemolytic analogue of VG16, shows significant antimicrobial activity against Gram-negative E. coli and plant pathogens X. oryzae and X. campestris, as well as against human fungal pathogens C. albicans and C. grubii. VG16KRKP is also capable of inhibiting bacterial disease progression in plants. The solution-NMR structure of VG16KRKP in lipopolysaccharide features a folded conformation with a centrally located turn-type structure stabilized by aromatic-aromatic packing interactions with extended N- and C-termini. The de novo design of VG16KRKP provides valuable insights into the development of more potent antibacterial and antiendotoxic peptides for the treatment of human and plant infections.

Five-Year Longitudinal Assessment (2008 to 2012) of E-101 Solution Activity against Clinical Target and Antimicrobial-Resistant Pathogens

PubMed Central

Pillar, Chris M.; Sahm, Daniel F.; O'Hanley, Peter; Stephens, Jackson T.

2014-01-01

This study summarizes the topical E-101 solution susceptibility testing results for 760 Gram-positive and Gram-negative target pathogens collected from 75 U.S. sites between 2008 and 2012 and 103 ESKAPE pathogens. E-101 solution maintained potent activity against all bacterial species studied for each year tested, with MICs ranging from <0.008 to 0.25 μg porcine myeloperoxidase (pMPO)/ml. These results confirm that E-101 solution retains its potent broad-spectrum activity against U.S. clinical isolates and organisms with challenging resistance phenotypes. PMID:24841272

The Central Hinge Link Truncation of the Antimicrobial Peptide Fowlicidin-3 Enhances Its Cell Selectivity without Antibacterial Activity Loss

PubMed Central

Qu, Pei; Gao, Wei; Chen, Huixian; Li, Dan; Yang, Na; Zhu, Jian; Li, Zhongqiu

2016-01-01

Antimicrobial peptides (AMPs) have been paid considerable attention because of their broad-spectrum antimicrobial activity and a reduced possibility of the development of bacterial drug resistance. Fowlicidin-3 (Fow-3) is an identified type of chicken cathelicidin AMP that has exhibited considerable antimicrobial activity and cytotoxicity. To reduce cell toxicity and improve cell selectivity, several truncated peptides of fowlicidin-3, Fow-3(1-15), Fow-3(1-19), Fow-3(1-15-20-27), and Fow-3(20-27), were synthesized. Our results indicated that neither the N- nor C-terminal segment alone [Fow-3(1-15), Fow-3(1-19), Fow-3(20-27)] was sufficient to confer antibacterial activity. However, Fow-3(1-19) with the inclusion of the central hinge link (-AGIN-) retained substantial cell toxicity, which other analogs lost. Fow-3(1-15-20-27) displayed potent antimicrobial activity for a wide range of Gram-negative and Gram-positive bacteria and no obvious hemolytic activity or cytotoxicity. The central link region was shown to be critically important in the function of cell toxicity but was not relevant to antibacterial activity. Fow-3(1-15-20-27) maintained antibacterial activity in the presence of physiological concentrations of salts. The results from fluorescence spectroscopy, scanning electron microcopy, and transmission electron microcopy showed that Fow-3(1-15-20-27) as well as fowlicidin-3 killed bacterial cells by increasing membrane permeability and damaging the membrane envelope integrity. Fow-3(1-15-20-27) could be a promising antimicrobial agent for clinical application. PMID:26902768

Small cationic antimicrobial peptidomimetics: emerging candidate for the development of potential anti-infective agents.

PubMed

Lohan, Sandeep; Bisht, Gopal Singh

2013-01-01

Rapid increase in the emergence and spread of microbes resistant to conventionally used antibiotics has become a major threat to global health care. Antimicrobial peptides (AMPs) are considered as a potential source of novel antibiotics because of their numerous advantages such as broad-spectrum activity, lower tendency to induce resistance, immunomodulatory response and unique mode of action. However, AMPs have several drawbacks such as; susceptibility to protease degradation, toxicity and high costs of manufacturing. Therefore, extensive research efforts are underway to explore the therapeutic potential of these fascinating natural compounds. This review highlights the potential of small cationic antimicrobial peptidomimetics (SCAMPs; M.W. ≅ 700 Da) as new generation antibiotics. In particular, we focused on recently identified small active pharmacophore from bulky templates of native AMPs, β-peptides, and lipopeptides. In addition, various design strategies recently undertaken to improve the physicochemical properties (proteolytic stability & plasma protein binding) of small cationic peptides have also been discussed.

Plants of the Melaleuca Genus as Antimicrobial Agents: From Farm to Pharmacy.

PubMed

Sharifi-Rad, Javad; Salehi, Bahare; Varoni, Elena Maria; Sharopov, Farukh; Yousaf, Zubaida; Ayatollahi, Seyed Abdulmajid; Kobarfard, Farzad; Sharifi-Rad, Mehdi; Afdjei, Mohammad Hossain; Sharifi-Rad, Majid; Iriti, Marcello

2017-10-01

Plants belonging to Melaleuca genus (Myrtaceae family) are native to Oceania, where they have been used for ages by Aborigine people in Australian traditional medicine, mainly because of their broad-spectrum antimicrobial activity. Although, M. linariifolia, M. dissitiflora, and other species of Melaleuca can also be used, the tea tree oil, an essential oil obtained from M. alternifolia shows the longest history of medicinal uses. Tea tree oil contains for the 80-90% several monoterpenes (terpinen-4-ol, α-terpinene, 1,8-cineol, p-cymene, α-terpineol, α-pinene, terpinolene, limonene, and sabinene). Sesquiterpenes and aromatic compounds further compose this oil. The essential oil of Melaleuca spp. has been reported to possess effective antibacterial and antifungal properties in vitro. In particular, data show that 1,8-cineol, terpinen-4-ol and methyl eugenol play the key role in mediating this oil's antimicrobial activity. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Improved antimicrobial compound production by a new isolate Streptomyces hygroscopicus MTCC 4003 using Plackett-Burman design and response Surface methodology.

PubMed

Singh, Neha; Rai, Vibhuti

2012-01-01

An active strain, isolated from soil of Chhattisgarh, India, showed broad-spectrum antimicrobial activity against various pathogenic bacteria and fungi in glucose soybean meal broth. Strain was characterized as Streptomyces hygroscopicus MTCC 4003 based on 16S rRNA sequencing from Microbial Type culture Collection (MTCC), IMTECH, Chandigarh, India. Identification of the purified antimicrobial compound was done by using Infra-red (IR), Mass, Ultraviolet (UV), 1H and 13C nuclear magnetic resonance (NMR) spectra. Plackett-Burman design (PBD) and response surface methodology (RSM) methods were used for the optimization of antibiotic production. Effects of the four medium components soybean meal, glucose, CaCO3 and MgSO4 showed positive effect on antibiotic production, were investigated with the help of PBD. The individual and interaction effects of the selected variables were determined by RSM using central composite design (CCD). Applying statistical design, antibiotic production was improved nearly ten times (412 mg/L) compared with unoptimized production medium (37 mg/L).

Design and synthesis of some new 2,3'-bipyridine-5-carbonitriles as potential anti-inflammatory/antimicrobial agents.

PubMed

Elzahhar, Perihan A; Elkazaz, Salwa; Soliman, Raafat; El-Tombary, Alaa A; Shaltout, Hossam A; El-Ashmawy, Ibrahim M; Abdel Wahab, Abeer E; El-Hawash, Soad A

2017-08-01

Inflammation may cause accumulation of fluid in the injured area, which may promote bacterial growth. Other reports disclosed that non-steroidal anti-inflammatory drugs may enhance progression of bacterial infection. This work describes synthesis of new series of 2,3'-bipyridine-5-carbonitriles as structural analogs of etoricoxib, linked at position-6 to variously substituted thio or oxo moieties. Biological screening results revealed that compounds 2b, 4b, 7e and 8 showed significant acute and chronic AI activities and broad spectrum of antimicrobial activity. In addition, similarity ensemble approach was applied to predict potential biological targets of the tested compounds. Then, pharmacophore modeling study was employed to determine the most important structural parameters controlling bioactivity. Moreover, title compounds showed physicochemical properties within those considered adequate for drug candidates. This study explored the potential of such series of compounds as structural leads for further modification to develop a new class of dual AI-antimicrobial agents.

Search for antibacterial and antifungal agents from selected Indian medicinal plants.

PubMed

Kumar, V Prashanth; Chauhan, Neelam S; Padh, Harish; Rajani, M

2006-09-19

A series of 61 Indian medicinal plants belonging to 33 different families used in various infectious disorders, were screened for their antimicrobial properties. Screening was carried out at 1000 and 500 microg/ml concentrations by agar dilution method against Bacillus cereus var mycoides, Bacillus pumilus, Bacillus subtilis, Bordetella bronchiseptica, Micrococcus luteus, Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Streptococcus faecalis, Candida albicans, Aspergillus niger and Saccharomyces cerevisiae. Twenty-eight plant extracts showed activity against at least one of the test organisms used in the screening. On the basis of the results obtained, we conclude that the crude extracts of Dorema ammoniacum, Sphaeranthus indicus, Dracaena cinnabari, Mallotus philippinensis, Jatropha gossypifolia, Aristolochia indica, Lantana camara, Nardostachys jatamansi, Randia dumetorum and Cassia fistula exhibited significant antimicrobial activity and properties that support folkloric use in the treatment of some diseases as broad-spectrum antimicrobial agents. This probably explains the use of these plants by the indigenous people against a number of infections.

Isolation, purification, and characterization of antimicrobial compound 6-[1,2-dimethyl-6-(2-methyl-allyloxy)-hexyl]-3-(2-methoxy-phenyl)-chromen-4-one from Penicillium sp. HT-28.

PubMed

Kaur, Harpreet; Arora, Daljit Singh; Sharma, Vishal

2014-08-01

A fungal culture (Penicillium sp., HT-28), isolated from soil has been evaluated for its bioactivity, which showed broad spectrum antimicrobial activity and was effective against methicillin-resistant Staphylococcus aureus (MRSA) also. Statistical optimization of the medium by response surface methodology (RSM) enhanced the antimicrobial activity up to 1.8-fold. Column chromatography was used to isolate the active compound (A), which was characterized to be 6-[1,2-dimethyl-6-(2-methyl-allyloxy)-hexyl]-3-(2-methoxy-phenyl)-chromen-4-one by various spectroscopic techniques such as infrared (IR), (1)H and (13)C nuclear magnetic resonance (NMR) spectra, and mass spectroscopy. Minimum inhibitory concentration (MIC) of the active compound (A) ranged from 0.5 to 15 μg/mL. Viable cell count studies of the active compound (A) showed S. aureus, Escherichia coli, Staphylococcus epidermidis, and Salmonella typhimurium 1 to be the most sensitive. The compound retained its bioactivity after treating it at 100 °C for 1 h. Furthermore, the compound (A) when tested for its biosafety was found neither to be cytotoxic nor mutagenic. The study demonstrated that an apparently novel compound isolated from Penicillium sp. (HT-28) seems to be a stable and potent antimicrobial.

Current state of a dual behaviour of antimicrobial peptides-Therapeutic agents and promising delivery vectors.

PubMed

Piotrowska, Urszula; Sobczak, Marcin; Oledzka, Ewa

2017-12-01

Micro-organism resistance is an important challenge in modern medicine due to the global uncontrolled use of antibiotics. Natural and synthetic antimicrobial peptides (AMPs) symbolize a new family of antibiotics, which have stimulated research and clinical interest as new therapeutic options for infections. They represent one of the most promising antimicrobial substances, due to their broad spectrum of biological activity, against bacteria, fungi, protozoa, viruses, yeast and even tumour cells. Besides, being antimicrobial, AMPs have been shown to bind and neutralize bacterial endotoxins, as well as possess immunomodulatory, anti-inflammatory, wound-healing, angiogenic and antitumour properties. In contrast to conventional antibiotics, which have very defined and specific molecular targets, host cationic peptides show varying, complex and very rapid mechanisms of actions that make it difficult to form an effective antimicrobial defence. Importantly, AMPs display their antimicrobial activity at micromolar concentrations or less. To do this, many peptide-based drugs are commercially available for the treatment of numerous diseases, such as hepatitis C, myeloma, skin infections and diabetes. Herein, we present an overview of the general mechanism of AMPs action, along with recent developments regarding carriers of AMPs and their potential applications in medical fields. © 2017 John Wiley & Sons A/S.

Synthetic hepcidin from fish: Uptake and protection against Vibrio anguillarum in sea bass (Dicentrarchus labrax).

PubMed

Álvarez, Claudio Andrés; Acosta, Félix; Montero, Daniel; Guzmán, Fanny; Torres, Elisa; Vega, Belinda; Mercado, Luis

2016-08-01

The generation of a variety of new therapeutic agents to control and reduce the effects of pathogen in aquaculture is urgently needed. The antimicrobial peptides (AMPs) are one of the major components of the innate defenses and typically have broad-spectrum antimicrobial activity. However, absorption and distributions of exogenous AMPs for therapeutics application on farmed fish species need to be studied. Previous studies in our laboratory have shown the properties of hepcidin as an effective antimicrobial peptide produced in fish in response to LPS and iron. Therefore, we decided to investigate the antimicrobial activity of four synthetic variants of hepcidin against Vibrio anguillarum in vitro, and using the more effective peptide we demonstrated the pathogen's ability to protect against the infection in European Sea bass. Additionally the uptake of this peptide after ip injection was demonstrated, reaching its distribution organs such as intestine, head kidney, spleen and liver. The synthetic peptide did not show cytotoxic effects and significantly reduced the accumulated mortalities percentage (23.5%) compared to the European Sea bass control (72.5%) at day 21. In conclusion, synthetic hepcidin shows antimicrobial activity against V. anguillarum and the in vivo experiments suggest that synthetic hepcidin was distributed trough the different organs in the fish. Thus, synthetic hepcidin antimicrobial peptide could have high potential for therapeutic application in farmed fish species. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of side group functionality and molecular weight on the activity of synthetic antimicrobial polypeptides.

PubMed

Engler, Amanda C; Shukla, Anita; Puranam, Sravanthi; Buss, Hilda G; Jreige, Nina; Hammond, Paula T

2011-05-09

The rapid emergence of antibiotic-resistant bacteria along with increasing difficulty in biofilm treatment has caused an immediate need for the development of new classes of antimicrobial therapeutics. We have developed a library of antimicrobial polypeptides, prepared by the ring-opening polymerization of γ-propargyl-L-glutamate N-carboxyanhydride and the alkyne-azide cycloaddition click reaction, which mimic the favorable characteristics of naturally occurring antimicrobial peptides (AmPs). AmPs are known not to cause drug resistance as well as prevent bacteria attachment on surfaces. The ease and scale of synthesis of the antimicrobial polypeptides developed here are significantly improved over the traditional Merrifield synthetic peptide approaches needed for naturally occurring antimicrobial peptides and avoids the unique challenges of biosynthetic pathways. The polypeptides range in length from 30 to 140 repeat units and can have varied side group functionality, including primary, secondary, tertiary, and quaternary amines with hydrocarbon side chains ranging from 1 to 12 carbons long. Overall, we find these polypeptides to exhibit broad-spectrum activity against both Gram positive and Gram negative bacteria, namely, S. aureus and E. coli , while having very low hemolytic activity. Many of the polypeptides can also be used as surface coatings to prevent bacterial attachment. The polypeptide library developed in this work addresses the need for effective biocompatible therapeutics for drug delivery and medical device coatings.

Food-grade antimicrobials potentiate the antibacterial activity of 1,2-hexanediol.

PubMed

Yogiara; Hwang, S J; Park, S; Hwang, J-K; Pan, J-G

2015-05-01

Preservative agents determining the shelf life of cosmetic products must have effective antimicrobial activity while meeting safety requirements for topical use. In this study, we determined the antimicrobial activity of 1,2-hexanediol against several Gram-positive and Gram-negative bacteria. Antimicrobial susceptibility tests have shown that 1,2-hexanediol exhibits broad-spectrum activity against Gram-positive and Gram-negative bacteria with MICs of 0·5-2% (v/v). The bactericidal concentration of 1,2-hexanediol was ranging from 1 to 2 × MIC as demonstrated by time-kill curve assay. A membrane depolarization assay showed that 1,2-hexanediol disrupted the cytoplasmic membrane potential. A checkerboard assay indicated that the effective concentration of 1,2-hexanediol was reduced up to 0·25-0·5 × MIC when combined with macelignan and octyl gallate against Gram-positive bacteria. However, this combination was not effective against Gram-negative bacteria. A turbidity reduction assay demonstrated that the combination of a high concentration of 1,2-hexanediol with food-grade antimicrobial compounds could trigger lytic activity towards Bacillus cereus cells. The remaining cell turbidity was 24·6 and 22·2% when 2% of 1,2-hexanediol was combined with 8 mg l(-1) octyl gallate or with 32 mg l(-1) macelignan respectively. This study showed that food-grade antimicrobial compounds may be used in combination with 1,2-hexanediol to increase its efficacy as a preservative agent in cosmetics. The antimicrobial activity of 1,2-hexanediol against Gram-positive and Gram-negative bacteria was potentiated with food-grade antimicrobials including xanthorrhizol, macelignan, panduratin A and octyl gallate, which have already been reported to display anti-inflammatory and other beneficial activities related to cosmetics. Therefore, the combination of 1,2-hexanediol and these food-grade antimicrobial agents would have benefits not only for increasing the antimicrobial activity but also in cosmetics use. © 2015 The Society for Applied Microbiology.

Antimicrobial Activity and Phytochemical Analysis of Organic Extracts from Cleome spinosa Jaqc.

PubMed Central

da Silva, Ana P. Sant'Anna; Nascimento da Silva, Luís C.; Martins da Fonseca, Caíque S.; de Araújo, Janete M.; Correia, Maria T. dos Santos; Cavalcanti, Marilene da Silva; Lima, Vera L. de Menezes

2016-01-01

Due to the use of Cleome spinosa Jacq. (Cleomaceae) in traditional medicine against inflammatory and infectious processes, this study evaluated the in vitro antimicrobial potential and phytochemical composition of extracts from its roots and leaves. From leaves (L) and roots (R) of C. spinosa different extracts were obtained (cyclohexane: ChL and ChR; chloroform: CL and CR; ethyl acetate: EAL and EAR, methanol: ML and MR). The antimicrobial activity was evaluated by the broth microdilution method to obtain the minimum inhibitory (MIC) and microbicidal (MMC) concentrations against 17 species, including bacteria and yeasts. Additionally, antimicrobial and combinatory effects with oxacillin were assessed against eight clinical isolates of Staphylococcus aureus. All C. spinosa extracts showed a broad spectrum of antimicrobial activity, as they have inhibited all tested bacteria and yeasts. This activity seems to be related to the phytochemicals (flavonoid, terpenoids and saponins) detected into the extracts of C. spinosa. ChL and CL extracts were the most actives, with MIC less than 1 mg/mL against S. aureus, Bacillus subtilis, and Micrococcus luteus. It is important to note that these concentrations are much lower than their 50% hemolysis concentration (HC50) values. Strong correlations were found between the average MIC against S. aureus and their phenolic (r = −0.89) and flavonoid content (r = −0.87), reinforcing the possible role of these metabolite classes on the antimicrobial activity of C. spinosa derived extracts. Moreover, CL and CR showed the best inhibitory activity against S. aureus clinical isolates, they also showed synergistic action with oxacillin against all these strains (at least at one combined proportion). These results encourage the identification of active substances which could be used as lead(s) molecules in the development of new antimicrobial drugs. PMID:27446005

A Novel Teaching Tool Combined With Active-Learning to Teach Antimicrobial Spectrum Activity.

PubMed

MacDougall, Conan

2017-03-25

Objective. To design instructional methods that would promote long-term retention of knowledge of antimicrobial pharmacology, particularly the spectrum of activity for antimicrobial agents, in pharmacy students. Design. An active-learning approach was used to teach selected sessions in a required antimicrobial pharmacology course. Students were expected to review key concepts from the course reader prior to the in-class sessions. During class, brief concept reviews were followed by active-learning exercises, including a novel schematic method for learning antimicrobial spectrum of activity ("flower diagrams"). Assessment. At the beginning of the next quarter (approximately 10 weeks after the in-class sessions), 360 students (three yearly cohorts) completed a low-stakes multiple-choice examination on the concepts in antimicrobial spectrum of activity. When data for students was pooled across years, the mean number of correct items was 75.3% for the items that tested content delivered with the active-learning method vs 70.4% for items that tested content delivered via traditional lecture (mean difference 4.9%). Instructor ratings on student evaluations of the active-learning approach were high (mean scores 4.5-4.8 on a 5-point scale) and student comments were positive about the active-learning approach and flower diagrams. Conclusion. An active-learning approach led to modestly higher scores in a test of long-term retention of pharmacology knowledge and was well-received by students.

A Novel Teaching Tool Combined With Active-Learning to Teach Antimicrobial Spectrum Activity

PubMed Central

2017-01-01

Objective. To design instructional methods that would promote long-term retention of knowledge of antimicrobial pharmacology, particularly the spectrum of activity for antimicrobial agents, in pharmacy students. Design. An active-learning approach was used to teach selected sessions in a required antimicrobial pharmacology course. Students were expected to review key concepts from the course reader prior to the in-class sessions. During class, brief concept reviews were followed by active-learning exercises, including a novel schematic method for learning antimicrobial spectrum of activity (“flower diagrams”). Assessment. At the beginning of the next quarter (approximately 10 weeks after the in-class sessions), 360 students (three yearly cohorts) completed a low-stakes multiple-choice examination on the concepts in antimicrobial spectrum of activity. When data for students was pooled across years, the mean number of correct items was 75.3% for the items that tested content delivered with the active-learning method vs 70.4% for items that tested content delivered via traditional lecture (mean difference 4.9%). Instructor ratings on student evaluations of the active-learning approach were high (mean scores 4.5-4.8 on a 5-point scale) and student comments were positive about the active-learning approach and flower diagrams. Conclusion. An active-learning approach led to modestly higher scores in a test of long-term retention of pharmacology knowledge and was well-received by students. PMID:28381885

Antimicrobial activity of eugenol and essential oils containing eugenol: A mechanistic viewpoint.

PubMed

Marchese, Anna; Barbieri, Ramona; Coppo, Erika; Orhan, Ilkay Erdogan; Daglia, Maria; Nabavi, Seyed Fazel; Izadi, Morteza; Abdollahi, Mohammad; Nabavi, Seyed Mohammad; Ajami, Marjan

2017-11-01

Eugenol is a hydroxyphenyl propene, naturally occurring in the essential oils of several plants belonging to the Lamiaceae, Lauraceae, Myrtaceae, and Myristicaceae families. It is one of the major constituents of clove (Syzygium aromaticum (L.) Merr. & L.M. Perry, Myrtaceae) oil and is largely used in both foods and cosmetics as a flavoring agent. A large body of recent scientific evidence supports claims from traditional medicine that eugenol exerts beneficial effects on human health. These effects are mainly associated with antioxidant and anti-inflammatory activities. Eugenol has also shown excellent antimicrobial activity in studies, being active against fungi and a wide range of gram-negative and gram-positive bacteria. The aim of this review is to analyze scientific data from the main published studies describing the antibacterial and antifungal activities of eugenol targeting different kind of microorganisms, such as those responsible for human infectious diseases, diseases of the oral cavity, and food-borne pathogens. This article also reports the effects of eugenol on multi-drug resistant microorganisms. On the basis of this collected data, eugenol represents a very interesting bioactive compound with broad spectrum antimicrobial activity against both planktonic and sessile cells belonging to food-decaying microorganisms and human pathogens.

Green synthesis of silver nanoparticles from Moringa oleifera leaf extracts and its antimicrobial potential

NASA Astrophysics Data System (ADS)

Moodley, Jerushka S.; Babu Naidu Krishna, Suresh; Pillay, Karen; Sershen; Govender, Patrick

2018-03-01

In this study we report on the synthesis of silver nanoparticles (AgNPs) from the leaf extracts of Moringa oleifera using sunlight irradiation as primary source of energy, and its antimicrobial potential. Silver nanoparticle formation was confirmed by surface plasmon resonance at 450 nm and 440 nm, respectively for both fresh and freeze-dried leaf samples. Crystanality of AgNPs was confirmed by transmission electron microscopy, scanning electron microscopy with energy dispersive x-ray spectroscopy and Fourier transform infrared (FTIR) spectroscopy analysis. FTIR spectroscopic analysis suggested that flavones, terpenoids and polysaccharides predominate and are primarily responsible for the reduction and subsequent capping of AgNPs. X-ray diffraction analysis also demonstrated that the size range of AgNPs from both samples exhibited average diameters of 9 and 11 nm, respectively. Silver nanoparticles showed antimicrobial activity on both bacterial and fungal strains. The biosynthesised nanoparticle preparations from M. oleifera leaf extracts exhibit potential for application as broad-spectrum antimicrobial agents.

The Freshwater Sponge Ephydatia fluviatilis Harbours Diverse Pseudomonas Species (Gammaproteobacteria, Pseudomonadales) with Broad-Spectrum Antimicrobial Activity

PubMed Central

Keller-Costa, Tina; Jousset, Alexandre; van Overbeek, Leo; van Elsas, Jan Dirk; Costa, Rodrigo

2014-01-01

Bacteria are believed to play an important role in the fitness and biochemistry of sponges (Porifera). Pseudomonas species (Gammaproteobacteria, Pseudomonadales) are capable of colonizing a broad range of eukaryotic hosts, but knowledge of their diversity and function in freshwater invertebrates is rudimentary. We assessed the diversity, structure and antimicrobial activities of Pseudomonas spp. in the freshwater sponge Ephydatia fluviatilis. Polymerase Chain Reaction – Denaturing Gradient Gel Electrophoresis (PCR-DGGE) fingerprints of the global regulator gene gacA revealed distinct structures between sponge-associated and free-living Pseudomonas communities, unveiling previously unsuspected diversity of these assemblages in freshwater. Community structures varied across E. fluviatilis specimens, yet specific gacA phylotypes could be detected by PCR-DGGE in almost all sponge individuals sampled over two consecutive years. By means of whole-genome fingerprinting, 39 distinct genotypes were found within 90 fluorescent Pseudomonas isolates retrieved from E. fluviatilis. High frequency of in vitro antibacterial (49%), antiprotozoan (35%) and anti-oomycetal (32%) activities was found among these isolates, contrasting less-pronounced basidiomycetal (17%) and ascomycetal (8%) antagonism. Culture extracts of highly predation-resistant isolates rapidly caused complete immobility or lysis of cells of the protozoan Colpoda steinii. Isolates tentatively identified as P. jessenii, P. protegens and P. oryzihabitans showed conspicuous inhibitory traits and correspondence with dominant sponge-associated phylotypes registered by cultivation-independent analysis. Our findings suggest that E. fluviatilis hosts both transient and persistent Pseudomonas symbionts displaying antimicrobial activities of potential ecological and biotechnological value. PMID:24533086

Anti-biofilm peptides as a new weapon in antimicrobial warfare.

PubMed

Pletzer, Daniel; Coleman, Shannon R; Hancock, Robert Ew

2016-10-01

Microorganisms growing in a biofilm state are very resilient in the face of treatment by many antimicrobial agents. Biofilm infections are a significant problem in chronic and long-term infections, including those colonizing medical devices and implants. Anti-biofilm peptides represent a very promising approach to treat biofilm-related infections and have an extraordinary ability to interfere with various stages of the biofilm growth mode. Anti-biofilm peptides possess promising broad-spectrum activity in killing both Gram-positive and Gram-negative bacteria in biofilms, show strong synergy with conventional antibiotics, and act by targeting a universal stringent stress response. Understanding downstream processes at the molecular level will help to develop and design peptides with increased activity. Anti-biofilm peptides represent a novel, exciting approach to treating recalcitrant bacterial infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Clinical studies on flomoxef in respiratory tract infections].

PubMed

Kanegae, H; Yamada, H; Yamaguchi, T; Kuroki, S; Katoh, O

1987-10-01

Flomoxef (FMOX, 6315-S) is a new oxacephem with a broad spectrum of antimicrobial activity. We used FMOX for treatment of 13 patients with respiratory tract infections including 4 cases of pneumonia, 5 of lung abscess and 4 of exacerbation of the chronic airway diseases. FMOX showed excellent in vitro antimicrobial activities against clinical isolates including 4 strains of Streptococcus pneumoniae, 2 strains of Haemophilus influenzae and each one strain of Escherichia coli and Klebsiella pneumoniae. Clinical responses were excellent in 3 cases, good in 7 and fair or poor in 3. No side effect was observed, but abnormal laboratory findings caused by FMOX administration were found in 2 cases; hypertransaminasemia and eosinophilia. However, neither of them was severe. From the above results, it is considered that FMOX will be useful for treatment of patients with respiratory tract infections.

Expression, purification and characterization of the recombinant cysteine-rich antimicrobial peptide snakin-1 in Pichia pastoris.

PubMed

Kuddus, Md Ruhul; Rumi, Farhana; Tsutsumi, Motosuke; Takahashi, Rika; Yamano, Megumi; Kamiya, Masakatsu; Kikukawa, Takashi; Demura, Makoto; Aizawa, Tomoyasu

2016-06-01

Snakin-1 (SN-1) is a small cysteine-rich plant antimicrobial peptide with broad spectrum antimicrobial activity which was isolated from potato (Solanum tuberosum). Here, we carried out the expression of a recombinant SN-1 in the methylotrophic yeast Pichia pastoris, along with its purification and characterization. A DNA fragment encoding the mature SN-1 was cloned into pPIC9 vector and introduced into P. pastoris. A large amount of pure recombinant SN-1 (approximately 40 mg/1L culture) was obtained from a fed-batch fermentation culture after purification with a cation exchange column followed by RP-HPLC. The identity of the recombinant SN-1 was verified by MALDI-TOF MS, CD and (1)H NMR experiments. All these data strongly indicated that the recombinant SN-1 peptide had a folding with six disulfide bonds that was identical to the native SN-1. Our findings showed that SN-1 exhibited strong antimicrobial activity against test microorganisms and produced very weak hemolysis of mammalian erythrocytes. The mechanism of its antimicrobial action against Escherichia coli was investigated by both outer membrane permeability assay and cytoplasmic membrane depolarization assay. These assays demonstrated that SN-1 is a membrane-active antimicrobial peptide which can disrupt both outer and cytoplasmic membrane integrity. This is the first report on the recombinant expression and purification of a fully active SN-1 in P. pastoris. Copyright © 2016 Elsevier Inc. All rights reserved.

A broad-spectrum antimicrobial activity of Bacillus subtilis RLID 12.1.

PubMed

Ramachandran, Ramya; Chalasani, Ajay Ghosh; Lal, Ram; Roy, Utpal

2014-01-01

In the present study, an attempt was made to biochemically characterize the antimicrobial substance from the soil isolate designated as RLID 12.1 and explore its potential applications in biocontrol of drug-resistant pathogens. The antimicrobial potential of the wild-type isolate belonging to the genus Bacillus was determined by the cut-well agar assay. The production of antimicrobial compound was recorded maximum at late exponential growth phase. The ultrafiltered concentrate was insensitive to organic solvents, metal salts, surfactants, and proteolytic and nonproteolytic enzymes. The concentrate was highly heat stable and active over a wide range of pH values. Partial purification, zymogram analysis, and TLC were performed to determine the preliminary biochemical nature. The molecular weight of the antimicrobial peptide was determined to be less than 2.5 kDa in 15% SDS-PAGE and in zymogram analysis against Streptococcus pyogenes. The N-terminal amino acid sequence by Edman degradation was partially determined to be T-P-P-Q-S-X-L-X-X-G, which shows very insignificant identity to other antimicrobial peptides from bacteria. The minimum inhibitory concentrations of dialysed and partially purified ion exchange fractions were determined against some selected gram-positive and gram-negative bacteria and some pathogenic yeasts. The presence of three important antimicrobial peptide biosynthesis genes ituc, fend, and bmyb was determined by PCR.

Essential oils and their principal constituents as antimicrobial agents for synthetic packaging films.

PubMed

Kuorwel, Kuorwel K; Cran, Marlene J; Sonneveld, Kees; Miltz, Joseph; Bigger, Stephen W

2011-01-01

Spices and herbal plant species have been recognized to possess a broad spectrum of active constituents that exhibit antimicrobial (AM) activity. These active compounds are produced as secondary metabolites associated with the volatile essential oil (EO) fraction of these plants. A wide range of AM agents derived from EOs have the potential to be used in AM packaging systems which is one of the promising forms of active packaging systems aimed at protecting food products from microbial contamination. Many studies have evaluated the AM activity of synthetic AM and/or natural AM agents incorporated into packaging materials and have demonstrated effective AM activity by controlling the growth of microorganisms. This review examines the more common synthetic and natural AM agents incorporated into or coated onto synthetic packaging films for AM packaging applications. The focus is on the widely studied herb varieties including basil, oregano, and thyme and their EOs. © 2011 Institute of Food Technologists®

Chemical Changes in Nonthermal Plasma-Treated N-Acetylcysteine (NAC) Solution and Their Contribution to Bacterial Inactivation.

PubMed

Ercan, Utku K; Smith, Josh; Ji, Hai-Feng; Brooks, Ari D; Joshi, Suresh G

2016-02-02

In continuation of our previous reports on the broad-spectrum antimicrobial activity of atmospheric non-thermal dielectric barrier discharge (DBD) plasma treated N-Acetylcysteine (NAC) solution against planktonic and biofilm forms of different multidrug resistant microorganisms, we present here the chemical changes that mediate inactivation of Escherichia coli. In this study, the mechanism and products of the chemical reactions in plasma-treated NAC solution are shown. UV-visible spectrometry, FT-IR, NMR, and colorimetric assays were utilized for chemical characterization of plasma treated NAC solution. The characterization results were correlated with the antimicrobial assays using determined chemical species in solution in order to confirm the major species that are responsible for antimicrobial inactivation. Our results have revealed that plasma treatment of NAC solution creates predominantly reactive nitrogen species versus reactive oxygen species, and the generated peroxynitrite is responsible for significant bacterial inactivation.

Chemical Changes in Nonthermal Plasma-Treated N-Acetylcysteine (NAC) Solution and Their Contribution to Bacterial Inactivation

PubMed Central

Ercan, Utku K.; Smith, Josh; Ji, Hai-Feng; Brooks, Ari D.; Joshi, Suresh G.

2016-01-01

In continuation of our previous reports on the broad-spectrum antimicrobial activity of atmospheric non-thermal dielectric barrier discharge (DBD) plasma treated N-Acetylcysteine (NAC) solution against planktonic and biofilm forms of different multidrug resistant microorganisms, we present here the chemical changes that mediate inactivation of Escherichia coli. In this study, the mechanism and products of the chemical reactions in plasma-treated NAC solution are shown. UV-visible spectrometry, FT-IR, NMR, and colorimetric assays were utilized for chemical characterization of plasma treated NAC solution. The characterization results were correlated with the antimicrobial assays using determined chemical species in solution in order to confirm the major species that are responsible for antimicrobial inactivation. Our results have revealed that plasma treatment of NAC solution creates predominantly reactive nitrogen species versus reactive oxygen species, and the generated peroxynitrite is responsible for significant bacterial inactivation. PMID:26832829

Antimicrobial compounds from seaweeds-associated bacteria and fungi.

PubMed

Singh, Ravindra Pal; Kumari, Puja; Reddy, C R K

2015-02-01

In recent decade, seaweeds-associated microbial communities have been significantly evaluated for functional and chemical analyses. Such analyses let to conclude that seaweeds-associated microbial communities are highly diverse and rich sources of bioactive compounds of exceptional molecular structure. Extracting bioactive compounds from seaweed-associated microbial communities have been recently increased due to their broad-spectrum antimicrobial activities including antibacterial, antifungal, antiviral, anti-settlement, antiprotozoan, antiparasitic, and antitumor. These allelochemicals not only provide protection to host from other surrounding pelagic microorganisms, but also ensure their association with the host. Antimicrobial compounds from marine sources are promising and priority targets of biotechnological and pharmaceutical applications. This review describes the bioactive metabolites reported from seaweed-associated bacterial and fungal communities and illustrates their bioactivities. Biotechnological application of metagenomic approach for identifying novel bioactive metabolites is also dealt, in view of their future development as a strong tool to discover novel drug targets from seaweed-associated microbial communities.

Antiseptics and Disinfectants: Activity, Action, and Resistance

PubMed Central

McDonnell, Gerald; Russell, A. Denver

1999-01-01

Antiseptics and disinfectants are extensively used in hospitals and other health care settings for a variety of topical and hard-surface applications. A wide variety of active chemical agents (biocides) are found in these products, many of which have been used for hundreds of years, including alcohols, phenols, iodine, and chlorine. Most of these active agents demonstrate broad-spectrum antimicrobial activity; however, little is known about the mode of action of these agents in comparison to antibiotics. This review considers what is known about the mode of action and spectrum of activity of antiseptics and disinfectants. The widespread use of these products has prompted some speculation on the development of microbial resistance, in particular whether antibiotic resistance is induced by antiseptics or disinfectants. Known mechanisms of microbial resistance (both intrinsic and acquired) to biocides are reviewed, with emphasis on the clinical implications of these reports. PMID:9880479

The assessment of the antibacterial and antifungal activities of aspirin, EDTA and aspirin-EDTA combination and their effectiveness as antibiofilm agents.

PubMed

Al-Bakri, A G; Othman, G; Bustanji, Y

2009-07-01

To evaluate the antimicrobial activities of aspirin, EDTA and an aspirin-EDTA (A-EDTA) combination against Pseudomonas aeruginosa, Escherichia coli and Candida albicans in planktonic and biofilm cultures. Minimal inhibitory concentrations (MIC) and minimal biocidal concentrations (MBC) were determined using twofold broth microdilution and viable counting methods, respectively. Aspirin's recorded MIC values ranged from 1.2 to 2.7 mg ml(-1). Checkerboard assay demonstrated a synergism in antimicrobial activity upon combination. Aspirin's minimal biofilm eradication concentration values (MBEC) against the established biofilms ranged between 1.35 and 3.83 mg ml(-1). A complete eradication of bacterial biofilms was achieved after a 4-h treatment with the A-EDTA combination. Both aspirin and EDTA possess broad-spectrum antimicrobial activity for both planktonic and biofilm cultures. Aspirin used at the MBEC for 24 h was successful in eradicating P. aeruginosa, E. coli and C. albicans biofilms established on abiotic surfaces. Moreover, the exposure to the A-EDTA combination (4 h) effected complete bacterial biofilm eradication. There is a continuous need for the discovery of new antimicrobial agents. Aspirin and EDTA are 'nonantibiotic drugs', the combination of which can be used successfully to treat and eradicate biofilms established on abiotic surfaces.

Will new generations of modified antimicrobial peptides improve their potential as pharmaceuticals?

PubMed Central

Brogden, Nicole K.; Brogden, Kim A.

2011-01-01

The concept of antimicrobial peptides (AMPs) as potent pharmaceuticals is firmly established in the literature, and most research articles on this topic conclude by stating that AMPs represent promising therapeutic agents against bacterial and fungal agents. Indeed, early research in this field showed that AMPs were diverse in nature, had high activities with low minimal inhibitory concentrations, had broad spectrums of activity against bacterial, fungal and viral pathogens, and could easily be manipulated to alter their specificities, reduce their cytotoxicities and increase their antimicrobial activities. Unfortunately, commercial development of these peptides, for even the simplest of applications, has been very limited. With some peptides there are obstacles with their manufacture, in vivo efficacy and in vivo retention. More recently, the focus has shifted. Contemporary research now uses a more sophisticated approach to develop AMPs that surmount many of these prior obstacles. AMP mimetics, hybrid AMPs, AMP congeners, cyclotides and stabilised AMPs, AMP conjugates and immobilised AMPs have all emerged with selective or ‘targeted’ antimicrobial activities, improved retention, or unique abilities that allow them to bind to medical or industrial surfaces. These groups of new peptides have creative medical and industrial application potentials to treat antibiotic-resistant bacterial infections and septic shock, to preserve food or to sanitise surfaces both in vitro and in vivo. PMID:21733662

Multifaceted defense against antagonistic microbes in developing offspring of the parasitoid wasp Ampulex compressa (Hymenoptera, Ampulicidae).

PubMed

Weiss, Katharina; Parzefall, Christopher; Herzner, Gudrun

2014-01-01

Effective antimicrobial strategies are essential adaptations of insects to protect themselves, their offspring, and their foods from microbial pathogens and decomposers. Larvae of the emerald cockroach wasp, Ampulex compressa, sanitize their cockroach hosts, Periplaneta americana, with a cocktail of nine antimicrobials comprising mainly (R)-(-)-mellein and micromolide. The blend of these antimicrobials has broad-spectrum antimicrobial activity. Here we explore the spatio-temporal pattern of deployment of antimicrobials during the development from egg to adult as well as their physico-chemical properties to assess how these aspects may contribute to the success of the antimicrobial strategy. Using gas chromatography/mass spectrometry (GC/MS) we show that larvae start sanitizing their food as soon as they have entered their host to feed on its tissue. Subsequently, they impregnate the cockroach carcass with antimicrobials to create a hygienic substrate for cocoon spinning inside the host. Finally, the antimicrobials are incorporated into the cocoon. The antimicrobial profiles on cockroach and wasp cocoon differed markedly. While micromolide persisted on the cockroaches until emergence of the wasps, solid-phase microextraction sampling and GC/MS analysis revealed that (R)-(-)-mellein vaporized from the cockroaches and accumulated in the enclosed nest. In microbial challenge assays (R)-(-)-mellein in the headspace of parasitized cockroaches inhibited growth of entomopathogenic and opportunistic microbes (Serratia marcescens, Aspergillus sydowii, Metarhizium brunneum). We conclude that, in addition to food sanitation, A. compressa larvae enclose themselves in two defensive walls by impregnating the cocoon and the cockroach cuticle with antimicrobials. On top of that, they use vaporous (R)-(-)-mellein to sanitize the nest by fumigation. This multifaceted antimicrobial defense strategy involving the spatially and temporally coordinated deployment of several antimicrobials in solution and vapor form has apparently evolved to reliably protect the larvae themselves and their food against a broad range of antagonistic microbes.

Multifaceted Defense against Antagonistic Microbes in Developing Offspring of the Parasitoid Wasp Ampulex compressa (Hymenoptera, Ampulicidae)

PubMed Central

Weiss, Katharina; Parzefall, Christopher; Herzner, Gudrun

2014-01-01

Effective antimicrobial strategies are essential adaptations of insects to protect themselves, their offspring, and their foods from microbial pathogens and decomposers. Larvae of the emerald cockroach wasp, Ampulex compressa, sanitize their cockroach hosts, Periplaneta americana, with a cocktail of nine antimicrobials comprising mainly (R)-(-)-mellein and micromolide. The blend of these antimicrobials has broad-spectrum antimicrobial activity. Here we explore the spatio-temporal pattern of deployment of antimicrobials during the development from egg to adult as well as their physico-chemical properties to assess how these aspects may contribute to the success of the antimicrobial strategy. Using gas chromatography/mass spectrometry (GC/MS) we show that larvae start sanitizing their food as soon as they have entered their host to feed on its tissue. Subsequently, they impregnate the cockroach carcass with antimicrobials to create a hygienic substrate for cocoon spinning inside the host. Finally, the antimicrobials are incorporated into the cocoon. The antimicrobial profiles on cockroach and wasp cocoon differed markedly. While micromolide persisted on the cockroaches until emergence of the wasps, solid-phase microextraction sampling and GC/MS analysis revealed that (R)-(-)-mellein vaporized from the cockroaches and accumulated in the enclosed nest. In microbial challenge assays (R)-(-)-mellein in the headspace of parasitized cockroaches inhibited growth of entomopathogenic and opportunistic microbes (Serratia marcescens, Aspergillus sydowii, Metarhizium brunneum). We conclude that, in addition to food sanitation, A. compressa larvae enclose themselves in two defensive walls by impregnating the cocoon and the cockroach cuticle with antimicrobials. On top of that, they use vaporous (R)-(-)-mellein to sanitize the nest by fumigation. This multifaceted antimicrobial defense strategy involving the spatially and temporally coordinated deployment of several antimicrobials in solution and vapor form has apparently evolved to reliably protect the larvae themselves and their food against a broad range of antagonistic microbes. PMID:24886721

Antimicrobial properties of honey.

PubMed

Israili, Zafar H

2014-01-01

Honey has been widely accepted as food and medicine by all generations, traditions, and civilizations, both ancient and modern. For at least 2700 years, honey has been used by humans to treat a variety of ailments through topical application, but only recently have the antiseptic and antimicrobial properties of honey been discovered. Honey has been reported to be effective in a number of human pathologies. Clinical studies have demonstrated that application of honey to severely infected cutaneous wounds rapidly clears infection from the wound and improves tissue healing. A large number of in vitro and limited clinical studies have confirmed the broad-spectrum antimicrobial (antibacterial, antifungal, antiviral, and antimycobacterial) properties of honey, which may be attributed to the acidity (low pH), osmotic effect, high sugar concentration, presence of bacteriostatic and bactericidal factors (hydrogen peroxide, antioxidants, lysozyme, polyphenols, phenolic acids, flavonoids, methylglyoxal, and bee peptides), and increase in cytokine release, and to immune modulating and anti-inflammatory properties of honey; the antimicrobial action involves several mechanisms. Despite a large amount of data confirming the antimicrobial activity of honey, there are no studies that support the systemic use of honey as an antibacterial agent.

What are the similarities and differences in antimicrobial prescribing between Australian public and private hospitals?

PubMed

Cotta, M O; Chen, C; Tacey, M; James, R S; Buising, K L; Marshall, C; Thursky, K A

2016-10-01

Identifying themes associated with inappropriate prescribing in Australian public and private hospitals will help target future antimicrobial stewardship initiatives. To describe current antimicrobial prescribing practices, identify similarities and differences between hospital sectors and provide target areas for improvement specific to each hospital sector. All hospitals included in the study were part of the 2014 national antimicrobial prescribing survey and conducted one of the following: a whole hospital point prevalence survey, serial point prevalence surveys or a sample of randomly selected patients. Data on the types of antibiotics used, their indications for use and the quality of prescription based on compliance with national and local prescribing guidelines were collected. Two hundred and two hospitals (166 public and 36 private) comprising 10 882 patients and 15 967 antimicrobial prescriptions were included. Public hospitals had higher proportions of prescriptions for treatment (81.5% vs 48.4%) and medical prophylaxis (8.8% and 4.6%), whilst private hospitals had significantly higher surgical prophylaxis use (9.6% vs 46.9%) (P < 0.001). In public hospitals, the main reasons for non-compliance of treatment prescriptions were spectrum being too broad (30.5%) while in private it was incorrect dosing. Prolonged duration was the main reason for non-compliance among surgical prophylaxis prescriptions in both types of hospitals. Australian hospitals need to target specific areas to improve antimicrobial use. Specifically, unnecessary broad-spectrum therapy should be a priority area in public hospitals, whilst emphasis on curtailing antimicrobial overuse in surgical prophylaxis needs to be urgently addressed across in the private hospital sector. © 2016 Royal Australasian College of Physicians.

Evaluation of empiric antibiotic de-escalation in febrile neutropenia.

PubMed

Kroll, Amanda L; Corrigan, Patricia A; Patel, Shejal; Hawks, Kelly G

2016-10-01

Up until 2010, the recommended duration of empiric broad-spectrum antibiotics for febrile neutropenia was until absolute neutrophil count (ANC) recovery. An updated guideline on the use of antimicrobial agents in neutropenic patients with cancer indicates that patients who have completed an appropriate treatment course of broad-spectrum antibiotics, with resolution of signs and symptoms of infection but persistent neutropenia, can be de-escalated to oral fluoroquinolone prophylaxis until ANC recovery. The primary objective of this retrospective investigation was to evaluate the safety and efficacy of de-escalating broad-spectrum antibiotics in patients remaining neutropenic after at least 14 days of empiric broadspectrum antibiotics for febrile neutropenia compared to patients continuing broad-spectrum antibiotics until ANC recovery. There were 16 patients (61.5%) in the comparator group who met the primary endpoint of remaining afebrile and without escalation of antibiotics for at least 72 hours after 14 days of broad-spectrum antibiotics and 21 patients (80.7%) in the de-escalation group who met the primary endpoint of remaining afebrile and without reinitiation of broad-spectrum antibiotics for at least 72 hours after de-escalation to levofloxacin therapy (p = 0.11). Mean total duration of broad-spectrum antibiotic therapy was 23.5 ± 1.5 days in the comparator group versus 22.2 ± 1.43 days in the de-escalation group (p = 0.39). Results of this investigation indicate that broad-spectrum antibiotics can be safely de-escalated to levofloxacin prophylaxis prior to ANC recovery in select patients. This practice may decrease the duration of broad-spectrum antibiotic exposure and associated complications. © The Author(s) 2015.

Reduced expression of dermcidin, a peptide active against propionibacterium acnes, in sweat of patients with acne vulgaris.

PubMed

Nakano, Toshiaki; Yoshino, Takashi; Fujimura, Takao; Arai, Satoru; Mukuno, Akira; Sato, Naoya; Katsuoka, Kensei

2015-09-01

Dermcidin (DCD), an antimicrobial peptide with a broad spectrum of activity against bacteria such as Propionibacterum acnes, is expressed constitutively in sweat in the absence of stimulation due to injury or inflammation. The aim of this study was to determine the relationship between DCD expression and acne vulgaris associated with P. acnes. The antimicrobial activity of recombinant full-length DCD (50 μg/ml) was 97% against Escherichia coli and 100% against Staphylococcus aureus. Antimicrobial activity against P. acnes ranged from 68% at 50 μg/ml DCD to 83% at 270 μg/ml DCD. DCD concentration in sweat from patients with acne vulgaris (median 9.8 μg/ml, range 6.9-95.3 μg/ml) was significantly lower than in healthy subjects (median 136.7 μg/ml, range 45.4-201.6 μg/ml) (p = 0.001). DCD demonstrated concentration-dependent, but partial, microbicidal activity against P. acnes. These results suggest that reduced DCD concentration in sweat in patients with inflammatory acne may permit proliferation of P. acnes in pilosebaceous units, resulting in progression of inflammatory acne.

Incidence and risk factors of surgical site infection in general surgery in a developing country.

PubMed

Alp, Emine; Elmali, Ferhan; Ersoy, Safiye; Kucuk, Can; Doganay, Mehmet

2014-04-01

To investigate the incidence of surgical site infections (SSIs) according to risk factors, etiological agents, antimicrobial resistance rates of pathogens, and antimicrobial prophylaxis (AMP) in a developing country. Prospective surveillance of SSIs was carried out in general surgery (GS) units between May 2005 and April 2009. SSI was diagnosed in 415 (10.8%) patients. Cefazolin was used as AMP in 780 (49%) operations, whereas broad-spectrum antibiotics were used in the remaining operations. AMP was administered for >24 h in 69 and 64% of the GS patients. The most significant risk factors for SSI after GS were total parenteral nutrition, transfusion, and a drainage catheter. The most common pathogen was Escherichia coli, but all the isolated pathogens were multiresistant. AMP is effective for reducing the risk of SSI; however, the prolonged use of AMP and broad-spectrum antibiotics may be associated with the emergence of resistant bacterial strains.

Morphological changes of the filamentous fungus Mucor mucedo and inhibition of chitin synthase activity induced by anethole.

PubMed

Yutani, Masahiro; Hashimoto, Yukie; Ogita, Akira; Kubo, Isao; Tanaka, Toshio; Fujita, Ken-ichi

2011-11-01

trans-Anethole (anethole), a major component of anise oil, has a broad antimicrobial spectrum with antimicrobial activity relatively weaker than those of well-known antibiotics, and significantly enhances the antifungal activity of polygodial and dodecanol against the baker's yeast Saccharomyces cerevisiae and human pathogenic yeast Candida albicans. However, the antifungal mechanism of anethole is unresolved. Anethole demonstrated antifungal activity against the filamentous fungus, Mucor mucedo IFO 7684, accompanied by hyphal morphological changes such as swollen hyphae at the tips. Its minimum growth inhibitory concentration was 0.625 mM. A hyperosmotic condition (1.2 M sorbitol) restricted the induction of morphological changes, while hypoosmotic treatment (distilled water) induced bursting of hyphal tips and leakage of cytoplasmic constituents. Furthermore, anethole dose-dependently inhibited chitin synthase (CHS) activity in permeabilized hyphae in an uncompetitive manner. These results suggest that the morphological changes of M. mucedo could be explained by the fragility of cell walls caused by CHS inhibition. Copyright © 2011 John Wiley & Sons, Ltd.

Biological evaluation of some new N-(2,6-dimethoxypyrimidinyl) thioureido benzenesulfonamide derivatives as potential antimicrobial and anticancer agents.

PubMed

Ghorab, Mostafa M; Alsaid, Mansour S; El-Gaby, Mohamed S A; Safwat, Nesreen A; Elaasser, Mahmoud M; Soliman, Aiten M

2016-11-29

A series of novel heterocyclic thioureas 3a-u containing sulfonamide moiety have been synthesized by the condensation of isothiocyanatobenzenesulfonamide 2 with a variety of heterocyclic amines. The newly synthesized heterocyclic thioureas were investigated for their antimicrobial and anticancer activity. The in vitro antibacterial and antifungal activity were done using well diffusion method. Interestingly, compounds 3j and 3m, showed similar or better activity compared with the reference drug against the tested microorganisms. Although, 3j was less active among its analogues to inhibit the breast carcinoma cells, it exhibit strong broad spectrum antimicrobial activities. However, The results of the cytotoxic activity revealed that compound 3p was the most active against the breast carcinoma cell line (MCF-7) giving promising IC 50 value of 1.72 μg/mL, compared with reference drug (5-flourouracil) with IC 50 value of 4.8 μg/mL. The most potent compounds in cytotoxic activity 3b and 3p were further docked inside the active site of CAIX and were found to exhibit a proper binding with the active site amino acids according to their bond lengths, angles and conformational energy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Isolation and characterization of large spectrum and multiple bacteriocin-producing Enterococcus faecium strain from raw bovine milk.

PubMed

Gaaloul, N; ben Braiek, O; Hani, K; Volski, A; Chikindas, M L; Ghrairi, T

2015-02-01

To assess the antimicrobial properties of lactic acid bacteria from Tunisian raw bovine milk. A bacteriocin-producing Enterococcus faecium strain was isolated from raw cow milk with activity against Gram-positive and Gram-negative bacteria. Antimicrobial substances produced by this strain were sensitive to proteolytic enzymes and were thermostable and resistant to a broad range of pH (2-10). Mode of action of antimicrobial substances was determined as bactericidal. Maximum activity was reached at the end of the exponential growth phase when checked against Listeria ivanovii BUG 496 (2366.62 AU ml(-1)). However, maximum antimicrobial activity against Pseudomonas aeruginosa 28753 was recorded at the beginning of the exponential growth phase. Enterococcus faecium GGN7 was characterized as free from virulence factors and was susceptible to tested antibiotics. PCR analysis of the micro-organism's genome revealed the presence of genes coding for enterocins A and B. Mass spectrometry analysis of RP-HPLC active fractions showed molecular masses corresponding to enterocins A (4835.77 Da) and B (5471.56 Da), and a peptide with a molecular mass of 3215.5 Da active only against Gram-negative indicator strains. The latter was unique in the databases. Enterococcus faecium GGN7 produces three bacteriocins with different inhibitory spectra. Based on its antimicrobial properties and safety, Ent. faecium GGN7 is potentially useful for food biopreservation. The results suggest the bacteriocins from GGN7 strain could be useful for food biopreservation. © 2014 The Society for Applied Microbiology.

The Central Hinge Link Truncation of the Antimicrobial Peptide Fowlicidin-3 Enhances Its Cell Selectivity without Antibacterial Activity Loss.

PubMed

Qu, Pei; Gao, Wei; Chen, Huixian; Li, Dan; Yang, Na; Zhu, Jian; Feng, Xingjun; Liu, Chunlong; Li, Zhongqiu

2016-05-01

Antimicrobial peptides (AMPs) have been paid considerable attention because of their broad-spectrum antimicrobial activity and a reduced possibility of the development of bacterial drug resistance. Fowlicidin-3 (Fow-3) is an identified type of chicken cathelicidin AMP that has exhibited considerable antimicrobial activity and cytotoxicity. To reduce cell toxicity and improve cell selectivity, several truncated peptides of fowlicidin-3, Fow-3(1-15), Fow-3(1-19), Fow-3(1-15-20-27), and Fow-3(20-27), were synthesized. Our results indicated that neither the N- nor C-terminal segment alone [Fow-3(1-15), Fow-3(1-19), Fow-3(20-27)] was sufficient to confer antibacterial activity. However, Fow-3(1-19) with the inclusion of the central hinge link (-AGIN-) retained substantial cell toxicity, which other analogs lost. Fow-3(1-15-20-27) displayed potent antimicrobial activity for a wide range of Gram-negative and Gram-positive bacteria and no obvious hemolytic activity or cytotoxicity. The central link region was shown to be critically important in the function of cell toxicity but was not relevant to antibacterial activity. Fow-3(1-15-20-27) maintained antibacterial activity in the presence of physiological concentrations of salts. The results from fluorescence spectroscopy, scanning electron microcopy, and transmission electron microcopy showed that Fow-3(1-15-20-27) as well as fowlicidin-3 killed bacterial cells by increasing membrane permeability and damaging the membrane envelope integrity. Fow-3(1-15-20-27) could be a promising antimicrobial agent for clinical application. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Biosynthesis of silver nanoparticles using lingonberry and cranberry juices and their antimicrobial activity.

PubMed

Puišo, Judita; Jonkuvienė, Dovilė; Mačionienė, Irena; Šalomskienė, Joana; Jasutienė, Ina; Kondrotas, Rokas

2014-09-01

In this study lingonberry and cranberry juices were used for silver nanoparticle synthesis. The berry juices were characterized by total phenolics, total anthocyanins and benzoic acid content, respectively 1.9-2.7mg/ml, 55.2-83.4mg/l and 590.8-889.2mg/l. The synthesis of silver nanoparticles was performed at room temperature assisting in solutions irradiated by ultraviolet for 30min. Ultraviolet-visible (UV-vis) spectroscopy and microscopy confirmed the formation of nanoparticles as well as the dark red color of colloid of silver samples showed the formation of stable nanoparticles. Broad localized surface plasmon resonance (LSPR) peaks in UV-vis spectra indicated the formation of polydispersive silver nanoparticles and LSPR was observed at 485nm and 520nm for the silver nanoparticles synthesis using lingonberry and cranberry juices, respectively. The antimicrobial activity of silver nanoparticles was determined against the reference strains of microorganisms that could be found in food products: Staphylococcus aureus ATCC 25923, Salmonella typhimurium ATCC 13076, Listeria monocytogenes ATCC 19111, Bacillus cereus ATCC 11778, Escherichia coli ATCC 25922, Bacillus subtilis ATCC 6633, Candida albicans ATCC 10231 and foodborne B. cereus producing and non-producing enterotoxins. Silver nanoparticles showed a broad spectrum of antimicrobial activity and were most active against S. aureus ATCC 25923, B. subtilis ATCC 6633 and B. cereus ATCC 11778 reference cultures, and less active against C. albicans ATCC 10231 and foodborne B. cereus. It can be concluded that lingonberry and cranberry juices could be used as bioreductants for silver ions. Copyright © 2014 Elsevier B.V. All rights reserved.

Structure-function analysis of Avian β-defensin-6 and β-defensin-12: role of charge and disulfide bridges.

PubMed

Yang, Ming; Zhang, Chunye; Zhang, Xuehan; Zhang, Michael Z; Rottinghaus, George E; Zhang, Shuping

2016-09-09

Avian beta-defensins (AvBD) are small, cationic, antimicrobial peptides. The potential application of AvBDs as alternatives to antibiotics has been the subject of interest. However, the mechanisms of action remain to be fully understood. The present study characterized the structure-function relationship of AvBD-6 and AvBD-12, two peptides with different net positive charges, similar hydrophobicity and distinct tissue expression profiles. AvBD-6 was more potent than AvBD-12 against E. coli, S. Typhimurium, and S. aureus as well as clinical isolates of extended spectrum beta lactamase (ESBL)-positive E. coli and K. pneumoniae. AvBD-6 was more effective than AvBD-12 in neutralizing LPS and interacting with bacterial genomic DNA. Increasing bacterial concentration from 10(5) CFU/ml to 10(9) CFU/ml abolished AvBDs' antimicrobial activity. Increasing NaCl concentration significantly inhibited AvBDs' antimicrobial activity, but not the LPS-neutralizing function. Both AvBDs were mildly chemotactic for chicken macrophages and strongly chemotactic for CHO-K1 cells expressing chicken chemokine receptor 2 (CCR2). AvBD-12 at higher concentrations also induced chemotactic migration of murine immature dendritic cells (DCs). Disruption of disulfide bridges abolished AvBDs' chemotactic activity. Neither AvBDs was toxic to CHO-K1, macrophages, or DCs. AvBDs are potent antimicrobial peptides under low-salt conditions, effective LPS-neutralizing agents, and broad-spectrum chemoattractant peptides. Their antimicrobial activity is positively correlated with the peptides' net positive charges, inversely correlated with NaCl concentration and bacterial concentration, and minimally dependent on intramolecular disulfide bridges. In contrast, their chemotactic property requires the presence of intramolecular disulfide bridges. Data from the present study provide a theoretical basis for the design of AvBD-based therapeutic and immunomodulatory agents.

Genome Sequence of Enterococcus faecium Strain ICIS 96 Demonstrating Intermicrobial Antagonism Associated with Bacteriocin Production.

PubMed

Pashkova, Tatiana M; Vasilchenko, Alexey S; Khlopko, Yuriy A; Kochkina, Elena E; Kartashova, Olga L; Sycheva, Maria V

2018-03-08

We report here the complete genome sequence of Enterococcus faecium strain ICIS 96, which was isolated from the feces of a horse. Bacteriological characterization of strain ICIS 96 revealed the absence of pathogenicity factors, while its spectrum of antagonistic activity was found to be broad, having activities associated with both Gram-positive and Gram-negative bacteria. Analysis of the E. faecium ICIS 96 genome revealed five genes associated with antimicrobial activity (enterocin [ent] A, ent B, lactobin A/cerein 7b, and ent L50 A/B). No genes that correlate with human pathogenicity were identified. Copyright © 2018 Pashkova et al.

Genome Sequence of Enterococcus faecium Strain ICIS 96 Demonstrating Intermicrobial Antagonism Associated with Bacteriocin Production

PubMed Central

Pashkova, Tatiana M.; Vasilchenko, Alexey S.; Khlopko, Yuriy A.; Kochkina, Elena E.; Kartashova, Olga L.

2018-01-01

ABSTRACT We report here the complete genome sequence of Enterococcus faecium strain ICIS 96, which was isolated from the feces of a horse. Bacteriological characterization of strain ICIS 96 revealed the absence of pathogenicity factors, while its spectrum of antagonistic activity was found to be broad, having activities associated with both Gram-positive and Gram-negative bacteria. Analysis of the E. faecium ICIS 96 genome revealed five genes associated with antimicrobial activity (enterocin [ent] A, ent B, lactobin A/cerein 7b, and ent L50 A/B). No genes that correlate with human pathogenicity were identified. PMID:29519833

Expression and purification of antimicrobial peptide adenoregulin with C-amidated terminus in Escherichia coli.

PubMed

Cao, Wei; Zhou, Yuxun; Ma, Yushu; Luo, Qingping; Wei, Dongzhi

2005-04-01

Adenoregulin is a 33 amino acid antimicrobial peptide isolated from the skin of the arboreal frog Phyllomedusa bicolor. Natural adenoregulin is synthesized with an amidated valine residue at C-terminus and shows lethal effects against filamentous fungi, as well as a broad spectrum of pathogenic microorganisms. A synthetic gene for adenoregulin (ADR) with an additional amino acid glutamine at C-terminus was cloned into pET32a vector to allow expression of ADR as a Trx fusion protein in Escherichia coli BL21(DE3). The resulting expression level of the fusion protein could reach up to 20% of the total cell proteins. The fusion protein could be purified effectively by Ni2+-chelating chromatography. Released from the fusion protein by enterokinase cleavage and purified to homogeneity, the recombinant ADR displayed antimicrobial activity similar to that of the synthetic ADR reported earlier. Comparing the antimicrobial activities of the recombinant adenoregulin with C-amidated terminus to that without an amidated C-terminus, we found that the amide of glutamine at C-terminus of ADR improved its potency on certain microorganisms such as Tritirachium album and Saccharomyces cerevisiae.

Effect of Antimicrobial Peptide KSL-W on Human Gingival Tissue and C. albicans Growth, Transition and Secreted Aspartyl Proteinase (SAPS) 2, 4, 5 and 6 Expressions

DTIC Science & Technology

2016-07-01

broad range of antibacterial activity and could play a role in preventing microbial infections(Decanis et al., 2009), (Zaslof, 2002). These antimicrobial...range of antibacterial activity and could play a role in preventing microbial infections(Decanis et al., 2009),(Zaslof, 2002). These antimicrobial...KSL- W (KKVVFWVKFK)(Na et al., 2007), which possess a broad range of antibacterial activity . It killed selected strains of non-oral and oral

A novel antimicrobial protein for plant protection consisting of a Xanthomonas oryzae harpin and active domains of cecropin A and melittin.

PubMed

Che, Yi-Zhou; Li, Yu-Rong; Zou, Hua-Song; Zou, Li-Fang; Zhang, Bing; Chen, Gong-You

2011-11-01

Discoveries about antimicrobial peptides and plant defence activators have made possible the de novo and rational design of novel peptides for use in crop protection. Here we report a novel chimeric protein, Hcm1, which was made by linking the active domains of cecropin A and melittin to the hypersensitive response (HR)-elicitor Hpa1 of Xanthomonas oryzae pv. oryzicola, the causal agent of rice bacterial leaf streak. The resulting chimeric protein maintained not only the HR-inducing property of the harpin, but also the antimicrobial activity of the cecropin A-melittin hybrid. Hcm1 was purified from engineered Escherichia coli and evaluated in terms of the minimal inhibitory concentration (MIC) and the 50% effective dose (ED(50)) against important plant pathogenic bacteria and fungi. Importantly, the protein acted as a potential pesticide by inducing disease resistance for viral, bacterial and fungal pathogens. This designed drug can be considered as a lead compound for use in plant protection, either for the development of new broad-spectrum pesticides or for expression in transgenic plants. © 2011 The Authors. Microbial Biotechnology © 2011 Society for Applied Microbiology and Blackwell Publishing Ltd.

Pharmacological Assessment of the Medicinal Potential of Acacia mearnsii De Wild.: Antimicrobial and Toxicity Activities

PubMed Central

Olajuyigbe, Olufunmiso O.; Afolayan, Anthony J.

2012-01-01

Acacia mearnsii De Wild. (Fabaceae) is a medicinal plant used in the treatment of microbial infections in South Africa without scientific validation of its bioactivity and toxicity. The antimicrobial activity of the crude acetone extract was evaluated by both agar diffusion and macrobroth dilution methods while its cytotoxicity effect was assessed with brine shrimp lethality assay. The study showed that both bacterial and fungal isolates were highly inhibited by the crude extract. The MIC values for the gram-positive bacteria (78.1–312.5) μg/mL, gram-negative bacteria (39.1–625) μg/mL and fungal isolates (625–5000) μg/mL differ significantly. The bacteria were more susceptible than the fungal strains tested. The antibiosis determination showed that the extract was more (75%) bactericidal than bacteriostatic (25%) and more fungicidal (66.67%) than fungistatic (33.33%). The cytotoxic activity of the extract was observed between 31.25 μg/mL and 500 μg/mL and the LC50 value (112.36 μg/mL) indicates that the extract was nontoxic in the brine shrimp lethality assay (LC50 > 100 μg/mL). These results support the use of A. mearnsii in traditional medicine for treatment of microbial infections. The extract exhibiting significant broad spectrum antimicrobial activity and nontoxic effects has potential to yield active antimicrobial compounds. PMID:22605976

Identification of structural traits that increase the antimicrobial activity of a chimeric peptide of human β-defensins 2 and 3.

PubMed

Spudy, Björn; Sönnichsen, Frank D; Waetzig, Georg H; Grötzinger, Joachim; Jung, Sascha

2012-10-12

Antimicrobial peptides participate in the first line of defence of many organisms against pathogens. In humans, the family of β-defensins plays a pivotal role in innate immunity. Two human β-defensins, β-defensin-2 and -3 (HBD2 and HBD3), show substantial sequence identity and structural similarity. However, HBD3 kills Staphylococcus (S.) aureus with a 4- to 8-fold higher efficiency compared to HBD2, whereas their activities against Escherichia (E.) coli are very similar. The generation of six HBD2/HBD3-chimeric molecules led to the identification of distinct molecular regions which mediate their divergent killing properties. One of the chimeras (chimera C3) killed both E. coli and S. aureus with an even higher efficacy compared to the wild-type molecules. Due to the broad spectrum of its antimicrobial activity against many human multidrug-resistant pathogens, this HBD2/HBD3-chimeric peptide represents a promising candidate for a new class of antibiotics. In order to investigate the structural basis of its exceptional antimicrobial activity, the peptide's tertiary structure was determined by NMR spectroscopy, which allowed its direct comparison to the published structures of HBD2 and HBD3 and the identification of the activity-increasing molecular features. Copyright © 2012 Elsevier Inc. All rights reserved.

In situ deposition of a personalized nanofibrous dressing via a handy electrospinning device for skin wound care

NASA Astrophysics Data System (ADS)

Dong, Rui-Hua; Jia, Yue-Xiao; Qin, Chong-Chong; Zhan, Lu; Yan, Xu; Cui, Lin; Zhou, Yu; Jiang, Xingyu; Long, Yun-Ze

2016-02-01

Current strategies for wound care provide limited relief to millions of patients who suffer from burns, chronic skin ulcers or surgical-related wounds. The goal of this work is to develop an in situ deposition of a personalized nanofibrous dressing via a handy electrospinning (e-spinning) device and evaluate its properties related to skin wound care. MCM-41 type mesoporous silica nanoparticles decorated with silver nanoparticles (Ag-MSNs) were prepared by a facile and environmentally friendly approach, which possessed long-term antibacterial activity and low cytotoxicity. Poly-ε-caprolactone (PCL) incorporated with Ag-MSNs was successfully electrospun (e-spun) into nanofibrous membranes. These in situ e-spun nanofibrous membranes allowed the continuous release of Ag ions and showed broad-spectrum antimicrobial activity against two common types of pathogens, Staphylococcus aureus and Escherichia coli. In addition, the in vivo studies revealed that these antibacterial nanofibrous membranes could reduce the inflammatory response and accelerate wound healing in Wistar rats. The above results strongly demonstrate that such patient-specific dressings could be broadly applied in emergency medical transport, hospitals, clinics and at the patients' home in the near future.Current strategies for wound care provide limited relief to millions of patients who suffer from burns, chronic skin ulcers or surgical-related wounds. The goal of this work is to develop an in situ deposition of a personalized nanofibrous dressing via a handy electrospinning (e-spinning) device and evaluate its properties related to skin wound care. MCM-41 type mesoporous silica nanoparticles decorated with silver nanoparticles (Ag-MSNs) were prepared by a facile and environmentally friendly approach, which possessed long-term antibacterial activity and low cytotoxicity. Poly-ε-caprolactone (PCL) incorporated with Ag-MSNs was successfully electrospun (e-spun) into nanofibrous membranes. These in situ e-spun nanofibrous membranes allowed the continuous release of Ag ions and showed broad-spectrum antimicrobial activity against two common types of pathogens, Staphylococcus aureus and Escherichia coli. In addition, the in vivo studies revealed that these antibacterial nanofibrous membranes could reduce the inflammatory response and accelerate wound healing in Wistar rats. The above results strongly demonstrate that such patient-specific dressings could be broadly applied in emergency medical transport, hospitals, clinics and at the patients' home in the near future. Electronic supplementary information (ESI) available: In situ electrospun antimicrobial nanofibrous dressing. See DOI: 10.1039/c5nr08367b

Anti-MRSA Activity of Fruiting Body Extracts of Spectacular Rustgill Mushroom, Gymnopilus junonius (Agaricomycetes).

PubMed

Barneche, Stephanie; Alborés, Silvana; Borthagaray, Graciela; Cerdeiras, María Pía; Vázquez, Alvaro

2017-01-01

Despite the great advances in chemotherapeutics, infectious diseases are still one of the leading causes of death worldwide. Among some of the clinically relevant pathogens, methicillin-resistant Staphylococcus aureus (MRSA) ranks as one of the most difficult bacteria to treat. It is a common cause of skin, soft-tissue, and endovascular infections, as well as pneumonia, septic arthritis, endocarditis, osteomyelitis, and sepsis. The research on Basidiomycota is extensive; many species show a broad spectrum of pharmacological activities, including antimicrobial activity. The vast majority of the literature to date generally focuses on screening the antibacterial properties of mushroom extracts. A gap still exists in the identification of the individual compounds responsible for these properties, and few low molecular weight compounds have been described. Gymnopilus junonius, the big laughter mushroom, grows wild in Uruguay, especially on Eucalyptus spp. plantations; it is known as the "eucalyptus fungus." In this work, we report the bioguided isolation, structural elucidation, and antistaphylococcal activity of the main antimicrobial components of fresh basidiocarps of G. junonius.

Genomics-Inspired Discovery of Three Antibacterial Active Metabolites, Aurantinins B, C, and D from Compost-Associated Bacillus subtilis fmb60.

PubMed

Yang, Jie; Zhu, Xiaoyu; Cao, Mingming; Wang, Changbao; Zhang, Chong; Lu, Zhaoxin; Lu, Fengxia

2016-11-23

Fmb60 is a wild-type Bacillus subtilis isolated from compost with significant broad-spectrum antimicrobial activities. Two novel PKS clusters were recognized in the genome sequence of fmb60, and then three polyene antibiotics, aurantinins B, C, and D, 1-3, were obtained by bioactivity-guided isolation from the fermentation of fmb60. The structures of aurantinins B-D were elucidated by LC-HRMS and NMR data analysis. Aurantinins C and D were identified as new antimicrobial compounds. The three aurantinins showed significant activity against multidrug-resistant Staphylococcus aureus and Clostridium sporogenes. However, aurantinins B-D did not exhibit any cytotoxicity (IC50 > 100 μg/mL) against LO2 and Caco2 cell lines by MTT assay. Furthermore, using S. aureus as a model bacterium to explore the antibacterial mechanism of aurantinins B-D, it was revealed that the bactericidal activity of aurantinins B-D was related to their ability to disrupt the cell membrane.

Highly potent antimicrobial peptides from N-terminal membrane-binding region of E. coli MreB.

PubMed

Saikia, Karabi; Sravani, Yalavarthi Durga; Ramakrishnan, Vibin; Chaudhary, Nitin

2017-02-23

Microbial pathogenesis is a serious health concern. The threat escalates as the existing conventional antimicrobials are losing their efficacy against the evolving pathogens. Peptides hold promise to be developed into next-generation antibiotics. Antimicrobial peptides adopt amphipathic structures that could selectively bind to and disrupt the microbial membranes. Interaction of proteins with membranes is central to all living systems and we reasoned that the membrane-binding domains in microbial proteins could be developed into efficient antimicrobials. This is an interesting approach as self-like sequences could elude the microbial strategies of degrading the antimicrobial peptides, one of the mechanisms of showing resistance to antimicrobials. We selected the 9-residue-long membrane-binding region of E. coli MreB protein. The 9-residue peptide (C-terminal amide) and its N-terminal acetylated analog displayed broad-spectrum activity, killing Gram-negative bacteria, Gram-positive bacteria, and fungi. Extension with a tryptophan residue at the N-terminus drastically improved the activity of the peptides with lethal concentrations ≤10 μM against all the organisms tested. The tryptophan-extended peptides caused complete killing of C. albicans as well as gentamicin and methicillin resistant S. aureus at 5 μM concentration. Lipid-binding studies and electron microscopic analyses of the peptide-treated microbes suggest membrane disruption as the mechanism of killing.

Gluconic acid produced by Gluconacetobacter diazotrophicus Pal5 possesses antimicrobial properties.

PubMed

Nieto-Peñalver, Carlos G; Savino, María J; Bertini, Elisa V; Sánchez, Leandro A; de Figueroa, Lucía I C

2014-09-01

Gluconic acid is produced in large quantities by the endophytic and diazotrophic bacterium Gluconacetobacter diazotrophicus Pal5. This organic acid derives from direct oxidation of glucose by a pyrroloquinoline-quinone-linked glucose dehydrogenase in this plant growth-promoting bacterium. In the present article, evidence is presented showing that gluconic acid is also responsible for the antimicrobial activity of G. diazotrophicus Pal5. The broad antagonistic spectrum includes Gram-positive and -negative bacteria. Eukaryotic microorganisms are more resistant to growth inhibition by this acid. Inhibition by gluconic acid can be modified through the presence of other organic acids. In contrast to other microorganisms, the Quorum Sensing system of G. diazotrophicus Pal5, a regulatory mechanism that plays a key role in several microbe-microbe interactions, is not related to gluconic acid production and the concomitant antagonistic activity. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Quinolone resistance.

PubMed

Brown, J C; Amyes, S G

1998-01-01

Quinolone antibacterial agents were first introduced into the clinical environment in the early 1960s. The first qumolone to be clinically used was nalidixic acid, which was used for the treatment of enteric and urinary tract infections. As a result of increased clinical resistance to this drug, its use has declined. However, the development of other chemically related antimicrobials with activities approaching one thousand times that of nalidixic acid has meant that bacteria resistant to this early nonfluormated quinolone are susceptible to the action of the newer fluoroquinolones. The fluoroquinolones, such as ciprofloxacin and ofloxacin, have proved to be potent antimicrobials and are used throughout the world in the treatment of bacterial infections, ranging from urinary tract infections to life-threatening septicemia. The clinical success of these agents can be attributed to their broad spectrum of activity, unique mechanism of action, good tissue distribution, and absorption from the gastrointestinal tract after oral admmistration (1).

Innovative biofilm inhibition and anti-microbial behavior of molybdenum sulfide nanostructures generated by microwave-assisted solvothermal route

NASA Astrophysics Data System (ADS)

Qureshi, Nilam; Patil, Rajendra; Shinde, Manish; Umarji, Govind; Causin, Valerio; Gade, Wasudev; Mulik, Uttam; Bhalerao, Anand; Amalnerkar, Dinesh P.

2015-03-01

The incessant use of antibiotics against infectious diseases has translated into a vicious circle of developing new antibiotic drug and its resistant strains in short period of time due to inherent nature of micro-organisms to alter their genes. Many researchers have been trying to formulate inorganic nanoparticles-based antiseptics that may be linked to broad-spectrum activity and far lower propensity to induce microbial resistance than antibiotics. The way-out approaches in this direction are nanomaterials based (1) bactericidal and (2) bacteriostatic activities. We, herein, present hitherto unreported observations on microbial abatement using non-cytotoxic molybdenum disulfide nanostructures (MSNs) which are synthesized using microwave assisted solvothermal route. Inhibition of biofilm formation using MSNs is a unique feature of our study. Furthermore, this study evinces antimicrobial mechanism of MSNs by reactive oxygen species (ROS) dependent generation of superoxide anion radical via disruption of cellular functions.

Delafloxacin for the treatment of respiratory and skin infections.

PubMed

Bassetti, Matteo; Della Siega, Paola; Pecori, Davide; Scarparo, Claudio; Righi, Elda

2015-03-01

There has been a striking increase in the emergence of multidrug-resistant pathogens in recent times. Delafloxacin is a novel, broad-spectrum fluoroquinolone with antimicrobial activity against resistant Gram-positive, Gram-negative and anaerobic organisms. It has the potential to treat a variety of infections including complicated skin and skin structure infections and respiratory tract infections. In this review, the authors report the microbiological spectrum of activity of delafloxacin as well as its pharmacokinetic characteristics. They also report the results of recent studies investigating its safety and efficacy. The profile of delafloxacin offers several advantages. Delafloxacin presents a broad spectrum of activity against pathogens involved in respiratory infections and complicated skin and skin structure infections (SSSIs), including methicillin-resistant Staphylococcus aureus. It has also shown activity against Gram-negative pathogens, such as quinolone-susceptible and -resistant strains of Escherichia coli and Klebsiella pneumoniae and quinolone-susceptible Pseudomonas aeruginosa. The availability of an oral formulation supports its use in sequential therapy. The efficacy and tolerability of delafloxacin have been demonstrated in Phase II clinical trials in comparison with moxifloxacin for respiratory infections and linezolid and vancomycin in SSSIs. Compared with other quinolones such as moxifloxacin, delafloxacin showed comparable efficacy and a lower rate of adverse effects. The results of new Phase III studies are awaited to confirm delafloxacin's future applications in the treatment of SSSIs.

In-vitro antimicrobial activity and identification of bioactive components using GC-MS of commercially available essential oils in Saudi Arabia.

PubMed

Ashraf, Syed Amir; Al-Shammari, Eyad; Hussain, Talib; Tajuddin, Shaikh; Panda, Bibhu Prasad

2017-11-01

This study was designed to evaluate antimicrobial activity and chemical composition of four different plant essential oils i.e. Ginger oil (GiO), Black seed oil (BSO), Oregano oil (OO) and Rose oil (RO) against different bacterial and fungal strains. Anti-microbial activities of selected essential oils were determined by the microbiological technique using Agar well diffusion assay. After in vitro study, most of the essential oils showed antimicrobial activity against all the selected pathogens. Among all the tested oils, GiO showed strong antimicrobial activity. GiO showed highest antimicrobial activity against Shigella (119.79%), Enteococcus hirae (110.61%) and Escherichia coli (106.02%), when compared with the tetracycline (50 µg/mL) activity. However, Antifungal activity of GiO was found to be present against Candida albicans and Aspergilluas flavus , when compared with clotrimazole (50 µg/mL) activity. Among all the selected bacteria, BSO showed maximum antimicrobial activity against the E. coli followed by Citrobacter freundii. Moreover, BSO had highest zone of inhibition against the C. ablicans (33.58%). OO indicated that, Shigella had the highest sensitivity (12.6 ± 0.58, 131.25%), followed by E. hirae (19.1 ± 0.61, 96.46%) and Salmonella typhi (15.2 ± 0.27, 83.06%) when compared with tetracycline activity. OO showed poor sensitivity against all the selected fungal strains. Furthermore, Gas Chromatography analysis revealed that, Gingerol (10.86%) was the chief chemical constituents found in GiO followed by α -Sesquiphellandrene (6.29%), Zingiberene (5.88%). While, BSO, OO and RO had higher percentage of p-Cymene (6.90%), Carvacrol (15.87%) and Citronellol (8.07%) respectively. The results exhibited that the essential oils used for this study was the richest source for antimicrobial activity which indicates the presence of broad spectrum antimicrobial compounds in these essential oils. Hence, essential oils and their components can be recommended for therapeutic purposes as source of an alternative medicine.

Microwave Assisted Synthesis of 1-[5-(Substituted Aryl)-1H-Pyrazol-3-yl]-3,5-Diphenyl-1H-1,2,4-Triazole as Antinociceptive and Antimicrobial Agents

PubMed Central

Khanage, Shantaram Gajanan; Mohite, Popat Baban; Pandhare, Ramdas Bhanudas; Raju, S. Appala

2014-01-01

Purpose: An efficient technique has been developed for microwave assisted synthesis of 1-[5-(substituted aryl)-1H-pyrazol-3-yl]-3,5-diphenyl-1H-1,2,4-triazole as antinociceptive and antimicrobial agents. Methods: The desired compounds (S1-S10) were synthesized by the microwave irradiation via cyclization of formerly synthesized chalcones of 3,5-diphenyl-1H-1,2,4-triazole and hydrazine hydrate in mild acidic condition. All newly synthesized compounds were subjected to study their antinociceptive and antimicrobial activity. The analgesic potential of compounds was tested by acetic acid induced writhing response and hot plate method. The MIC values for antimicrobial activity were premeditated by liquid broth method. Results: The compounds S1, S2, S4, S6 and S10 were found to be excellent peripherally acting analgesic agents when tested on mice by acetic acid induced writhing method and compounds S3, S6 and S1 at dose level of 100 mg/kg were exhibited superior centrally acting antinociceptive activity when tested by Eddy’s hot plate method. In antimicrobial activity compound S10 found to be broad spectrum antibacterial agent at MIC value of 15.62 µg/ml and compound S6 was exhibited antifungal potential at 15.62 µg/mL on both fungal strains. Conclusion: Some novel pyrazoles clubbed with 1,2,4-triazole derivatives were synthesized and evaluated as possible antimicrobial, centrally and peripherally acting analgesics. PMID:24511473

Antimicrobial activity of stingless bee (Trigona sp.) propolis used in the folk medicine of Western Maharashtra, India.

PubMed

Choudhari, Milind K; Punekar, Sachin A; Ranade, Ramchandra V; Paknikar, Kishore M

2012-05-07

Stingless bee (Trigona sp.) propolis is widely used in the folk medicine of Western Maharashtra, India to treat a variety of ailments. To determine the chemical composition and evaluate the antimicrobial activity of Indian stingless bee propolis. Chemical composition of the ethanolic extract of propolis (EEP) was determined by GC-MS analysis. A range of bacteria including multidrug resistant (MDR) cultures as well as a yeast strain was tested for antimicrobial activity using EEP. MIC, MBC, MFC, Kill curves and post agent effect (PAE) of the EEP were assessed using standard microbiological methods. GC-MS analysis revealed that propolis contained 24 compounds (9 known and 15 newly reported). Many of these were known bioactive compounds, including antimicrobials. The MICs of EEP were in the range of 1.21-9.75μg/mL while the MBCs/MFC were between 2.43 and 19.5μg/mL. The time required to achieve 90% (1 log(10)) reduction in culture growth ranged between 1.06 and 3.53h at their respective MIC values. PAE for all the cultures was >24h. Indian stingless bee propolis has a complex nature with 24 chemical compounds. It has a potent broad-spectrum antimicrobial activity. The latter finding, in conjunction with other bioactive properties, could provide a scientific basis to its popular use in the Indian folk medicine. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Multifunctional Polyphenols- and Catecholamines-Based Self-Defensive Films for Health Care Applications.

PubMed

Dhand, Chetna; Harini, Sriram; Venkatesh, Mayandi; Dwivedi, Neeraj; Ng, Alice; Liu, Shouping; Verma, Navin Kumar; Ramakrishna, Seeram; Beuerman, Roger W; Loh, Xian Jun; Lakshminarayanan, Rajamani

2016-01-20

In an era of relentless evolution of antimicrobial resistance, there is an increasing demand for the development of efficient antimicrobial coatings or surfaces for food, biomedical, and industrial applications. This study reports the laccase-catalyzed room-temperature synthesis of mechanically robust, thermally stable, broad spectrum antimicrobial films employing interfacial interactions between poly(vinyl alcohol), PVA, and 14 naturally occurring catecholamines and polyphenols. The oxidative products of catecholamines and polyphenols reinforce the PVA films and also alter their surface and bulk properties. Among the catecholamines-reinforced films, optimum surface and bulk properties can be achieved by the oxidative products of epinephrine. For polyphenols, structure-property correlation reveals an increase in surface roughness and elasticity of PVA films with increasing number of phenolic groups in the precursors. Interestingly, PVA films reinforced with oxidized/polymerized products of pyrogallol (PG) and epinephrine (EP) display potent antimicrobial activity against pathogenic Gram-positive and Gram-negative strains, whereas hydroquinone (HQ)-reinforced PVA films display excellent antimicrobial properties against Gram-positive bacteria only. We further demonstrate that HQ and PG films retain their antimicrobial efficacy after steam sterilization. With an increasing trend of giving value to natural and renewable resources, our results have the potential as durable self-defensive antimicrobial surfaces/films for advanced healthcare and industrial applications.

Identification and characterization of antimicrobial peptides from the skin of the endangered frog Odorrana ishikawae.

PubMed

Iwakoshi-Ukena, Eiko; Ukena, Kazuyoshi; Okimoto, Aiko; Soga, Miyuki; Okada, Genya; Sano, Naomi; Fujii, Tamotsu; Sugawara, Yoshiaki; Sumida, Masayuki

2011-04-01

The endangered anuran species, Odorrana ishikawae, is endemic to only two small Japanese Islands, Amami and Okinawa. To assess the innate immune system in this frog, we investigated antimicrobial peptides in the skin using artificially bred animals. Nine novel antimicrobial peptides containing the C-terminal cyclic heptapeptide domain were isolated on the basis of antimicrobial activity against Escherichia coli. The peptides were members of the esculentin-1 (two peptides), esculentin-2 (one peptide), palustrin-2 (one peptide), brevinin-2 (three peptides) and nigrocin-2 (two peptides) antimicrobial peptide families. They were named esculentin-1ISa, esculentin-1ISb, esculentin-2ISa, palustrin-2ISa, brevinin-2ISa, brevinin-2ISb, brevinin-2ISc, nigrocin-2ISa and nigrocin-2ISb. Peptide primary structures suggest a close relationship with the Asian odorous frogs, Odorrana grahami and Odorrana hosii. These antimicrobial peptides possessed a broad-spectrum of growth inhibition against five microorganisms (E. coli, Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus subtilis and Candida albicans). Nine different cDNAs encoding the precursor proteins were also cloned and showed that the precursor proteins exhibited a signal peptide, an N-terminal acidic spacer domain, a Lys-Arg processing site and an antimicrobial peptide at the C-terminus. Copyright © 2010 Elsevier Inc. All rights reserved.

Impact of a Prospective Audit and Feedback Antimicrobial Stewardship Program at a Veterans Affairs Medical Center: A Six-Point Assessment

PubMed Central

Morrill, Haley J.; Caffrey, Aisling R.; Gaitanis, Melissa M.; LaPlante, Kerry L.

2016-01-01

Background Prospective audit and feedback is a core antimicrobial stewardship program (ASP) strategy; however its impact is difficult to measure. Methods Our quasi-experimental study measured the effect of an ASP on clinical outcomes, antimicrobial use, resistance, costs, patient safety (adverse drug events [ADE] and Clostridium difficile infection [CDI]), and process metrics pre- (9/10–10/11) and post-ASP (9/12–10/13) using propensity adjusted and matched Cox proportional-hazards regression models and interrupted time series (ITS) methods. Results Among our 2,696 patients, median length of stay was 1 day shorter post-ASP (5, interquartile range [IQR] 3–8 vs. 4, IQR 2–7 days, p<0.001). Mortality was similar in both periods. Mean broad-spectrum (-11.3%), fluoroquinolone (-27.0%), and anti-pseudomonal (-15.6%) use decreased significantly (p<0.05). ITS analyses demonstrated a significant increase in monthly carbapenem use post-ASP (trend: +1.5 days of therapy/1,000 patient days [1000PD] per month; 95% CI 0.1–3.0). Total antimicrobial costs decreased 14%. Resistance rates did not change in the one-year post-ASP period. Mean CDI rates/10,000PD were low pre- and post-ASP (14.2 ± 10.4 vs. 13.8 ± 10.0, p = 0.94). Fewer patients experienced ADEs post-ASP (6.0% vs. 4.4%, p = 0.06). Conclusions Prospective audit and feedback has the potential to improve antimicrobial use and outcomes, and contain bacterial resistance. Our program demonstrated a trend towards decreased length of stay, broad-spectrum antimicrobial use, antimicrobial costs, and adverse events. PMID:26978263

Short AntiMicrobial Peptides (SAMPs) as a class of extraordinary promising therapeutic agents.

PubMed

Ramesh, Suhas; Govender, Thavendran; Kruger, Hendrik G; de la Torre, Beatriz G; Albericio, Fernando

2016-07-01

The emergence of multidrug resistant bacteria has a direct impact on global public health because of the reduced potency of existing antibiotics against pathogens. Hence, there is a pressing need for new drugs with different modes of action that can kill microorganisms. Antimicrobial peptides (AMPs) can be regarded as an alternative tool for this purpose because they are proven to have therapeutic effects with broad-spectrum activities. There are some hurdles in using AMPs as clinical candidates such as toxicity, lack of stability and high budgets required for manufacturing. This can be overcome by developing shorter and more easily accessible AMPs, the so-called Short AntiMicrobial Peptides (SAMPs) that contain between two and ten amino acid residues. These are emerging as an attractive class of therapeutic agents with high potential for clinical use and possessing multifunctional activities. In this review we attempted to compile those SAMPs that have exhibited biological properties which are believed to hold promise for the future. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

An environmentally benign antimicrobial nanoparticle based ...

EPA Pesticide Factsheets

Silver nanoparticles have antibacterial properties but their use has been a cause for concern because they persist in the environment. Here we show that lignin nanoparticles infused with silver ions and coated with a cationic polyelectrolyte layer form a biodegradable and green alternative to silver nanoparticles. The polyelectrolyte layer promotes the adhesion of the particles to bacterial cell membranes and together with silver ions can kill a broad spectrum of bacteria, including Escherichia coli, Pseudomonas aeruginosa and quaternary-amine-resistant Ralstonia sp. Ion depletion studies showed that the bioactivity of these nanoparticles is time-limited because of the desorption of silver ions. High-throughput bioactivity screening did not reveal increased toxicity of the particles when compared to an equivalent mass of metallic silver nanoparticles or silver nitrate solution. Our results demonstrate that the application of green chemistry principles may allow the synthesis of nanoparticles with biodegradable cores that have higher antimicrobial activity and smaller environmental impact than metallic silver nanoparticles. Our results demonstrate that the application of green chemistry principles may allow the synthesis of nanoparticles with biodegradable cores that have higher antimicrobial activity and smaller environmental impact than metallic silver nanoparticles

Antimicrobial peptides as potential anti-biofilm agents against multidrug-resistant bacteria.

PubMed

Chung, Pooi Yin; Khanum, Ramona

2017-08-01

Bacterial resistance to commonly used drugs has become a global health problem, causing increased infection cases and mortality rate. One of the main virulence determinants in many bacterial infections is biofilm formation, which significantly increases bacterial resistance to antibiotics and innate host defence. In the search to address the chronic infections caused by biofilms, antimicrobial peptides (AMP) have been considered as potential alternative agents to conventional antibiotics. Although AMPs are commonly considered as the primitive mechanism of immunity and has been extensively studied in insects and non-vertebrate organisms, there is now increasing evidence that AMPs also play a crucial role in human immunity. AMPs have exhibited broad-spectrum activity against many strains of Gram-positive and Gram-negative bacteria, including drug-resistant strains, and fungi. In addition, AMPs also showed synergy with classical antibiotics, neutralize toxins and are active in animal models. In this review, the important mechanisms of action and potential of AMPs in the eradication of biofilm formation in multidrug-resistant pathogen, with the goal of designing novel antimicrobial therapeutics, are discussed. Copyright © 2017. Published by Elsevier B.V.

Protein-only, antimicrobial peptide-containing recombinant nanoparticles with inherent built-in antibacterial activity.

PubMed

Serna, Naroa; Sánchez-García, Laura; Sánchez-Chardi, Alejandro; Unzueta, Ugutz; Roldán, Mónica; Mangues, Ramón; Vázquez, Esther; Villaverde, Antonio

2017-09-15

The emergence of bacterial antibiotic resistances is a serious concern in human and animal health. In this context, naturally occurring cationic antimicrobial peptides (AMPs) might play a main role in a next generation of drugs against bacterial infections. Taking an innovative approach to design self-organizing functional proteins, we have generated here protein-only nanoparticles with intrinsic AMP microbicide activity. Using a recombinant version of the GWH1 antimicrobial peptide as building block, these materials show a wide antibacterial activity spectrum in absence of detectable toxicity on mammalian cells. The GWH1-based nanoparticles combine clinically appealing properties of nanoscale materials with full biocompatibility, structural and functional plasticity and biological efficacy exhibited by proteins. Because of the largely implemented biological fabrication of recombinant protein drugs, the protein-based platform presented here represents a novel and scalable strategy in antimicrobial drug design, that by solving some of the limitations of AMPs offers a promising alternative to conventional antibiotics. The low molecular weight antimicrobial peptide GWH1 has been engineered to oligomerize as self-assembling protein-only nanoparticles of around 50nm. In this form, the peptide exhibits potent and broad antibacterial activities against both Gram-positive and Gram-negative bacteria, without any harmful effect over mammalian cells. As a solid proof-of-concept, this finding strongly supports the design and biofabrication of nanoscale antimicrobial materials with in-built functionalities. The protein-based homogeneous composition offer advantages over alternative materials explored as antimicrobial agents, regarding biocompatibility, biodegradability and environmental suitability. Beyond the described prototype, this transversal engineering concept has wide applicability in the design of novel nanomedicines for advanced treatments of bacterial infections. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The synthetic human beta-defensin-3 C15 peptide exhibits antimicrobial activity against Streptococcus mutans, both alone and in combination with dental disinfectants.

PubMed

Ahn, Ki Bum; Kim, A Reum; Kum, Kee-Yeon; Yun, Cheol-Heui; Han, Seung Hyun

2017-10-01

Streptococcus mutans is a major etiologic agent of human dental caries that forms biofilms on hard tissues in the human oral cavity, such as tooth and dentinal surfaces. Human β-defensin-3 (HBD3) is a 45-amino-acid natural antimicrobial peptide that has broad spectrum antimicrobial activity against bacteria and fungi. A synthetic peptide consisting of the C-terminal 15 amino acids of HBD3 (HBD3-C15) was recently shown to be sufficient for its antimicrobial activity. Thus, clinical applications of this peptide have garnered attention. In this study, we investigated whether HBD3-C15 inhibits the growth of the representative cariogenic pathogen Streptococcus mutans and its biofilm formation. HBD3-C15 inhibited bacterial growth, exhibited bactericidal activity, and attenuated bacterial biofilm formation in a dose-dependent manner. HBD3-C15 potentiated the bactericidal and anti-biofilm activity of calcium hydroxide (CH) and chlorhexidine digluconate (CHX), which are representative disinfectants used in dental clinics, against S. mutans. Moreover, HBD3-C15 showed antimicrobial activity by inhibiting biofilm formation by S. mutans and other dentinophilic bacteria such as Enterococcus faecalis and Streptococcus gordonii, which are associated with dental caries and endodontic infection, on human dentin slices. These effects were observed for HBD3-C15 alone and for HBD3-C15 in combination with CH or CHX. Therefore, we suggest that HBD3-C15 is a potential alternative or additive disinfectant that can be used for the treatment of oral infectious diseases, including dental caries and endodontic infections.

Targeted simplification versus antipseudomonal broad-spectrum beta-lactams in patients with bloodstream infections due to Enterobacteriaceae (SIMPLIFY): a study protocol for a multicentre, open-label, phase III randomised, controlled, non-inferiority clinical trial

PubMed Central

López-Cortés, Luis Eduardo; Rosso-Fernández, Clara; Núñez-Núñez, María; Lavín-Alconero, Lucía; Bravo-Ferrer, José; Barriga, Ángel; Delgado, Mercedes; Lupión, Carmen; Retamar, Pilar; Rodríguez-Baño, Jesús

2017-01-01

Introduction Within the context of antimicrobial stewardship programmes, de-escalation of antimicrobial therapy is one of the proposed strategies for reducing the unnecessary use of broad-spectrum antibiotics (BSA). The empirical treatment of nosocomial and some healthcare-associated bloodstream infections (BSI) frequently includes a beta-lactam with antipseudomonal activity as monotherapy or in combination with other drugs, so there is a great opportunity to optimise the empirical therapy based on microbiological data. De-escalation is assumed as standard of care for experts in infectious diseases. However, it is less frequent than it would desirable. Methods and analysis The SIMPLIFY trial is a multicentre, open-label, non-inferiority phase III randomised controlled clinical trial, designed as a pragmatic ‘real-practice’ trial. The aim of this trial is to demonstrate the non-inferiority of de-escalation from an empirical beta-lactam with antipseudomonal activity to a targeted narrow-spectrum antimicrobial in patients with BSI due to Enterobacteriaceae. The primary outcome is clinical cure, which will be assessed at the test of cure visit. It will be conducted at 19 Spanish public and university hospitals. Ethics and dissemination Each participating centre has obtained the approval of the ethics review committee, the agreement of the directors of the institutions and authorisation from the Spanish Regulatory Agency (Agencia Española del Medicamento y Productos Sanitarios). Data will be presented at international conferences and published in peer-reviewed journals. Discussion Strategies to reduce the use of BSA should be a priority. Most of the studies that support de-escalation are observational, retrospective and heterogeneous. A recent Cochrane review stated that well-designed clinical trials should be conducted to assess the safety and efficacy of de-escalation. Trial registration number The European Union Clinical Trials Register: EudraCT number 2015-004219-19. Clinical trials.gov: NCT02795949. Protocol version: V.2.0, dated 16 May 2016. All items from the WHO Trial Registration Data Set are included in the registry. PMID:28601833

Will new generations of modified antimicrobial peptides improve their potential as pharmaceuticals?

PubMed

Brogden, Nicole K; Brogden, Kim A

2011-09-01

The concept of antimicrobial peptides (AMPs) as potent pharmaceuticals is firmly established in the literature, and most research articles on this topic conclude by stating that AMPs represent promising therapeutic agents against bacterial and fungal pathogens. Indeed, early research in this field showed that AMPs were diverse in nature, had high activities with low minimal inhibitory concentrations, had broad spectrums of activity against bacterial, fungal and viral pathogens, and could easily be manipulated to alter their specificities, reduce their cytotoxicities and increase their antimicrobial activities. Unfortunately, commercial development of these peptides, for even the simplest of applications, has been very limited. With some peptides there are obstacles with their manufacture, in vivo efficacy and in vivo retention. More recently, the focus has shifted. Contemporary research now uses a more sophisticated approach to develop AMPs that surmount many of these prior obstacles. AMP mimetics, hybrid AMPs, AMP congeners, cyclotides and stabilised AMPs, AMP conjugates and immobilised AMPs have all emerged with selective or 'targeted' antimicrobial activities, improved retention, or unique abilities that allow them to bind to medical or industrial surfaces. These groups of new peptides have creative medical and industrial application potentials to treat antibiotic-resistant bacterial infections and septic shock, to preserve food or to sanitise surfaces both in vitro and in vivo. Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Mechanism of action and in vitro activity of short hybrid antimicrobial peptide PV3 against Pseudomonas aeruginosa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Memariani, Hamed; Shahbazzadeh, Delavar; Sabatier, Jean-Marc

Antimicrobial peptides are attractive candidates for developing novel therapeutic agents, since they are lethal to a broad spectrum of pathogens and have a unique low tendency for resistance development. In this study, mechanism of action and in vitro anti-pseudomonal activity of previously designed short hybrid antimicrobial peptide PV3 were investigated. Compared to ceftazidime, PV3 had not only higher antibacterial activity but also faster bactericidal activity. PV3 reduced biofilm biomass and viability of biofilm embedded bacteria in a concentration-dependent manner. Although the antimicrobial activity of PV3 was reduced in Mueller-Hinton broth (MHB) containing human serum, it was still active enough to eradicationmore » of bacteria at low concentrations. Compared with standard condition (MHB only), there was no significant decrease in antibacterial activity of PV3 against P. aeruginosa strains under 150 mM NaCl (p = 0.615) and 1 mM MgCl{sub 2} (p = 0.3466). Fluorescence microscopy and field emission scanning electron microscopy further indicated that PV3 killed bacteria by disrupting the cell membrane. Since PV3 has potent anti-pseudomonal activity and has little cytotoxicity in vitro, it seems plausible that the peptide should be further investigated with animal studies to support future pharmacological formulations and potential topical applications. - Highlights: • PV3 killed Pseudomonas aeruginosa by membrane-disrupting mechanism. • PV3 reduced biofilm biomass and viability of biofilm embedded bacteria in a concentration-dependent manner. • Short hybrid antimicrobial peptide PV3 exhibited higher and faster bactericidal activity comparing to ceftazidime.« less

Effects of specific egg yolk antibody (IgY) on the quality and shelf life of refrigerated Paralichthys olivaceus.

PubMed

Xu, Yafu; Lin, Hong; Sui, Jianxin; Cao, Limin

2012-04-01

The spoilage of fishery food has been attributed to limited types of microorganisms called specific spoilage organisms (SSO). Unlike traditional food-preserving techniques which usually exploit broad-spectrum antimicrobial agents, here, based on the specific antimicrobial activity of egg yolk antibodies (IgY) against two SSO in refrigerated fish (Shewanella putrefaciens and Pseudomonas fluorescens), a novel strategy for fish preservation was suggested and evaluated. During storage of Paralichthys olivaceus fillets at 4 ± 1 °C, the bacteria growth (including total microorganisms and the two SSO) in test groups was significantly inhibited in comparison to that of controls (P < 0.05). This antibacterial activity of the specific IgY was also confirmed by chemical analysis (pH, total volatile base nitrogen and 2-thiobarbituric acid value) and sensory evaluation, and the shelf life of samples was extended approximately from 9 days to 12-15 days in the presence of the specific IgY. These results indicated a significant antimicrobial activity of the anti-SSO IgY for refrigerated fish products, which allowed us to suggest its potential as a bio-preservative for seafood. Copyright © 2011 Society of Chemical Industry.

Production of Biologically Active Cecropin A Peptide in Rice Seed Oil Bodies

PubMed Central

Izquierdo, Esther; Campo, Sonia; Badosa, Esther; Rossignol, Michel; Montesinos, Emilio; San Segundo, Blanca; Coca, María

2016-01-01

Cecropin A is a natural antimicrobial peptide that exhibits fast and potent activity against a broad spectrum of pathogens and neoplastic cells, and that has important biotechnological applications. However, cecropin A exploitation, as for other antimicrobial peptides, is limited by their production and purification costs. Here, we report the efficient production of this bioactive peptide in rice bran using the rice oleosin 18 as a carrier protein. High cecropin A levels were reached in rice seeds driving the expression of the chimeric gene by the strong embryo-specific oleosin 18 own promoter, and targeting the peptide to the oil body organelle as an oleosin 18-cecropin A fusion protein. The accumulation of cecropin A in oil bodies had no deleterious effects on seed viability and seedling growth, as well as on seed yield. We also show that biologically active cecropin A can be easily purified from the transgenic rice seeds by homogenization and simple flotation centrifugation methods. Our results demonstrate that the oleosin fusion technology is suitable for the production of cecropin A in rice seeds, which can potentially be extended to other antimicrobial peptides to assist their exploitation. PMID:26760761

Rapid extraction of Amomum tsao-ko essential oil and determination of its chemical composition, antioxidant and antimicrobial activities.

PubMed

Cui, Qi; Wang, Li-Tao; Liu, Ju-Zhao; Wang, Hui-Mei; Guo, Na; Gu, Cheng-Bo; Fu, Yu-Jie

2017-09-01

A simple, green and efficient extraction method named modified-solvent free microwave extraction (M-SFME) was employed for the extraction of essential oils (EOs) from Amomun tsao-ko. The process of M-SFME was optimized with the prominent preponderance of such higher extraction yield (1.13%) than those of solvent free microwave extraction (SFME, 0.91%) and hydrodistillation (HD, 0.84%) under the optimal parameters. Thirty-four volatile substances representing 95.4% were identified. The IC 50 values of EOs determined by DPPH radical scavenging activity and β-carotene/linoleic acid bleaching assay were 5.27 and 0.63mg/ml. Furthermore, the EOs exhibited moderate to potent broad-spectrum antimicrobial activity against all tested strains including five gram-positive and two gram-negative bacteria (MIC: 2.94-5.86mg/ml). In general, M-SFME is a potential and desirable alternative for the extraction of EOs from aromatic herbs, and the EOs obtained from A. tsao-ko can be explored as a potent natural antimicrobial and antioxidant preservative ingredient in food industry from the technological and economical points of view. Copyright © 2017 Elsevier B.V. All rights reserved.

Interdigital athlete's foot: new concepts in pathogenesis.

PubMed

Leyden, J J; Kligman, A M

1977-06-01

In our view, interdigital athlete's foot usually begins with invasion of the horny layer by dermatophytes. Because of hot weather, sweating, exercise, or tight shoes, enough moisture accumulates to stimulate an overgrowth of bacteria. Large numbers of normally resident aerobic diphtheroids cause the common wet, macerated type of athlete's foot, while an overgrowth of Gram-negative organisms, such as Pseudomonas and Proteus, is responsible for the more serious cases. The dry, scaly type (dermatophytosis simplex) often alternates with the wet, macerated type (dermatophytosis complex). Flare-ups are common in summer and can be experimentally induced by occlusion of fungus-infected feet. Suppression of bacteria is essential in treating symptomatic athlete's foot. This can be accomplished by exposing the feet to air (eg, wearing sandals) to enhance evaporation of water and prevent the accumulation of excess moisture that stimulates bacterial overgrowth. Topical antibiotics are another approach, with the ideal perhaps being an agent with both broad-spectrum antibacterial and antifungal activity. The newer imidazoles are broad-spectrum compounds but have limited activity against Gram-negative organisms. Our agent of choice, aluminum chloride, combines broad-spectrum antimicrobial activity with chemical drying, a two-pronged attack. We view drying as the decisive element. We doubt that any local treatment can permanently eradicate athlete's foot. Potent antifungal agents can virtually exterminate interdigital dermatophytes, but the inevitable presence of infection in the nails or on the soles assures reinfection. In shoe-wearing populations living in temperate climates, interdigital athlete's foot is mainly a seasonal disease. The various therapies discussed provide a variety of approaches to prevent or ameliorate hot-weather exacerbations.

In vitro evaluation of broad-spectrum beta-lactams in the philippines medical centers: role of fourth-generation cephalosporins. The Philippines Antimicrobial Resistance Study Group.

PubMed

Johnson, D M; Biedenbach, D J; Jones, R N

1999-12-01

Cefepime is a potent broad-spectrum "fourth-generation" cephalosporin. The in vitro activity of cefepime was compared to that of cefpirome, ceftazidime, ceftriaxone, imipenem, and piperacillin/tazobactam in a multilaboratory (nine medical centers) Philippine surveillance project from March through October 1998. A total of 626 Gram-positive and Gram-negative organisms (10 species groups) were tested by the Etest method (AB BIODISK, Solna, Sweden) with results validated by current quality control strain analysis. The overall rank order of usable spectrum of activity was imipenem (4.2% resistance), cefepime (4.5%), cefpirome (5.0%), piperacillin/tazobactam (5.8%) > ceftriaxone (11.2%) > ceftazidime (15.3%), and results did not differ significantly between medical centers. Ceftazidime-resistant Escherichia coli and Klebsiella spp. occurred at rates of 13.3% and 31.1%, respectively, indicating extended-spectrum beta-lactamase (ESBL) activity. Imipenem (100% susceptible), cefepime, and cefpirome (both > or = 97.8% susceptible) were active in vitro against these ESBL phenotypes. Organisms with ceftazidime and/or ceftriaxone-resistant profiles consistent for hyper-production of Amp C cephalosporinases were detected at high rates among the Citrobacter spp. (29.2%) and Enterobacter spp. (45.8%); however, imipenem (100.0% susceptible) and cefepime (98.9%) remained active. Cefepime and imipenem (both 87.5% susceptible) were the most active agents tested against Acinetobacter spp. whereas piperacillin/tazobactam was most effective against P. aeruginosa (80.0% susceptible). Most tested beta-lactams (except ceftazidime) were active versus oxacillin-susceptible staphylococci. These data should be used as a guide for treatment selection with beta-lactam compounds in the Philippines and to serve as a resistance benchmark in comparisons with future studies in this nation.

Antimicrobial efficacy of eucalyptus oil and 1,8-cineole alone and in combination with chlorhexidine digluconate against microorganisms grown in planktonic and biofilm cultures.

PubMed

Hendry, E R; Worthington, T; Conway, B R; Lambert, P A

2009-12-01

Effective disinfection and antisepsis is pivotal in preventing infections within the healthcare setting. Chlorhexidine digluconate (CHG) is a widely used disinfectant/antiseptic possessing broad-spectrum antimicrobial activity; however, its penetration into bacterial biofilms and human skin is poor. The aim of this study was to investigate the antimicrobial efficacy of crude eucalyptus oil (EO) and its main component 1,8-cineole (a recognized permeation enhancer), alone and in combination with CHG, against a panel of clinically relevant microorganisms grown in planktonic and biofilm cultures. MICs and minimum bactericidal/fungicidal concentrations were determined for each microorganism grown in suspension and biofilm using microbroth dilution and ATP bioluminescence, respectively. Chequerboard assays were used to determine synergistic, indifferent or antagonistic interactions between CHG and EO or 1,8-cineole. Antimicrobial activity was demonstrated by CHG, EO and 1,8-cineole; however, CHG was significantly more active against microorganisms in both planktonic and biofilm modes of growth (P < 0.05). Crude EO was significantly more efficacious against microorganisms grown in suspension compared with 1,8-cineole (P < 0.05). Synergistic activity was demonstrated between CHG and both EO and 1,8-cineole against suspensions of Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Escherichia coli and Candida albicans, and biofilm cultures of MRSA and Pseudomonas aeruginosa. In conclusion, CHG may be combined with either crude EO or its major component 1,8-cineole for enhanced, synergistic antimicrobial activity against a wide range of microorganisms in planktonic and biofilm modes of growth; however, the superior antimicrobial efficacy associated with crude EO alone, compared with 1,8-cineole, favours its combination with CHG.

Resistance of nanobacteria isolated from urinary and kidney stones to broad-spectrum antibiotics.

PubMed

Sardarabadi, Hadi; Mashreghi, Mansour; Jamialahmadi, Khadijeh; Dianat, Tahere

2014-08-01

Nanoscopic life forms called Nanobacteria or calcifying nanoparticles (CNP) are unconventional agents. These novel organisms are very small (0.1 to 0.5 microns) and possess unusual properties such as high resistance to heat and routine antimicrobial agents. Nanobacteria are 100 times smaller than bacteria and protected by a shell of apatite, so they could be as candidate for emerging and progress of in vivo pathological calcification. In this study, the inhibitory effect of broad-spectrum antibiotics on growth of these new forms of life has been investigated. Powdered urinary and kidney stones were demineralized with HCl and neutralized with appropriate buffers and became filtered. Finally suspension was incubated in DMEM medium with Fetal Bovine Serum (FBS) and broad-spectrum antibiotics (100U/ml for penicillin and 100μg/ml for streptomycin) for 60 days. In the presence of broad-spectrum antibiotics, Scanning Electron Micrographs (SEM) showed a spherical shape of these nanobacteria. Also, Energy Dispersive X-ray spectroscopy (EDS) showed a pick for calcium and phosphor. Transmission Electron Microscopy (TEM) results illustrated cover around the nanobacteria. The growth of calcifying nanoparticles after adding the broad-spectrum antibiotics may be due to their apatite hard shells supporting them against penetration of the antibiotics.

Identification of a novel fungus, Trichoderma asperellum GDFS1009, and comprehensive evaluation of its biocontrol efficacy.

PubMed

Wu, Qiong; Sun, Ruiyan; Ni, Mi; Yu, Jia; Li, Yaqian; Yu, Chuanjin; Dou, Kai; Ren, Jianhong; Chen, Jie

2017-01-01

Due to its efficient broad-spectrum antimicrobial activity, Trichoderma has been established as an internationally recognized biocontrol fungus. In this study, we found and identified a novel strain of Trichoderma asperellum, named GDFS1009. The mycelium of T. asperellum GDFS1009 exhibits a high growth rate, high sporulation capacity, and strong inhibitory effects against pathogens that cause cucumber fusarium wilt and corn stalk rot. T. asperellum GDFS1009 secretes chitinase, glucanase, and protease, which can degrade the cell walls of fungi and contribute to mycoparasitism. The secreted xylanases are good candidates for inducing plant resistance and enhancing plant immunity against pathogens. RNA sequencing (RNA-seq) and gas chromatography-mass spectrometry (GC-MS) showed that T. asperellum GDFS1009 produces primary metabolites that are precursors of antimicrobial compounds; it also produces a variety of antimicrobial secondary metabolites, including polyketides and alkanes. In addition, this study speculated the presence of six antimicrobial peptides via ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF-MS/MS). Future studies should focus on these antimicrobial metabolites for facilitating widespread application in the field of agricultural bio-control.

Identification of a novel fungus, Trichoderma asperellum GDFS1009, and comprehensive evaluation of its biocontrol efficacy

PubMed Central

Wu, Qiong; Sun, Ruiyan; Ni, Mi; Yu, Jia; Li, Yaqian; Yu, Chuanjin; Dou, Kai; Ren, Jianhong; Chen, Jie

2017-01-01

Due to its efficient broad-spectrum antimicrobial activity, Trichoderma has been established as an internationally recognized biocontrol fungus. In this study, we found and identified a novel strain of Trichoderma asperellum, named GDFS1009. The mycelium of T. asperellum GDFS1009 exhibits a high growth rate, high sporulation capacity, and strong inhibitory effects against pathogens that cause cucumber fusarium wilt and corn stalk rot. T. asperellum GDFS1009 secretes chitinase, glucanase, and protease, which can degrade the cell walls of fungi and contribute to mycoparasitism. The secreted xylanases are good candidates for inducing plant resistance and enhancing plant immunity against pathogens. RNA sequencing (RNA-seq) and gas chromatography-mass spectrometry (GC-MS) showed that T. asperellum GDFS1009 produces primary metabolites that are precursors of antimicrobial compounds; it also produces a variety of antimicrobial secondary metabolites, including polyketides and alkanes. In addition, this study speculated the presence of six antimicrobial peptides via ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF-MS/MS). Future studies should focus on these antimicrobial metabolites for facilitating widespread application in the field of agricultural bio-control. PMID:28644879

Nanotechnology Formulations for Antibacterial Free Fatty Acids and Monoglycerides.

PubMed

Jackman, Joshua A; Yoon, Bo Kyeong; Li, Danlin; Cho, Nam-Joon

2016-03-03

Free fatty acids and monoglycerides have long been known to possess broad-spectrum antibacterial activity that is based on lytic behavior against bacterial cell membranes. Considering the growing challenges of drug-resistant bacteria and the need for new classes of antibiotics, the wide prevalence, affordable cost, and broad spectrum of fatty acids and monoglycerides make them attractive agents to develop for healthcare and biotechnology applications. The aim of this review is to provide a brief introduction to the history of antimicrobial lipids and their current status and challenges, and to present a detailed discussion of ongoing research efforts to develop nanotechnology formulations of fatty acids and monoglycerides that enable superior in vitro and in vivo performance. Examples of nano-emulsions, liposomes, solid lipid nanoparticles, and controlled release hydrogels are presented in order to highlight the potential that lies ahead for fatty acids and monoglycerides as next-generation antibacterial solutions. Possible application routes and future directions in research and development are also discussed.

Novel Naja atra cardiotoxin 1 (CTX-1) derived antimicrobial peptides with broad spectrum activity

PubMed Central

Santospirito, Davide; Polverini, Eugenia; Flisi, Sara; Cavirani, Sandro; Taddei, Simone

2018-01-01

Naja atra subsp. atra cardiotoxin 1 (CTX-1), produced by Chinese cobra snakes, belonging to Elapidae family, is included in the three-finger toxin family and exerts high cytotoxicity and antimicrobial activity too. Using as template mainly the tip and the subsequent β-strand of the first “finger” of this toxin, different sequences of 20 amino acids linear peptides have been designed in order to avoid toxic effects but to maintain or even strengthen the partial antimicrobial activity already seen for the complete toxin. As a result, the sequence NCP-0 (Naja Cardiotoxin Peptide-0) was designed as ancestor and subsequently 4 other variant sequences of NCP-0 were developed. These synthesized variant sequences have shown microbicidal activity towards a panel of reference and field strains of Gram-positive and Gram-negative bacteria. The sequence named NCP-3, and its variants NCP-3a and NCP-3b, have shown the best antimicrobial activity, together with low cytotoxicity against eukaryotic cells and low hemolytic activity. Bactericidal activity has been demonstrated by minimum bactericidal concentration (MBC) assay at values below 10 μg/ml for most of the tested bacterial strains. This potent antimicrobial activity was confirmed even for unicellular fungi Candida albicans, Candida glabrata and Malassezia pachydermatis (MBC 50–6.3 μg/ml), and against the fast-growing mycobacteria Mycobacterium smegmatis and Mycobacterium fortuitum. Moreover, NCP-3 has shown virucidal activity on Bovine Herpesvirus 1 (BoHV1) belonging to Herpesviridae family. The bactericidal activity is maintained even in a high salt concentration medium (125 and 250 mM NaCl) and phosphate buffer with 20% Mueller Hinton (MH) medium against E. coli, methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa reference strains. Considering these in vitro obtained data, the search for active sequences within proteins presenting an intrinsic microbicidal activity could provide a new way for discovering a large number of novel and promising antimicrobial peptides families. PMID:29364903

Fungal Root Microbiome from Healthy and Brittle Leaf Diseased Date Palm Trees (Phoenix dactylifera L.) Reveals a Hidden Untapped Arsenal of Antibacterial and Broad Spectrum Antifungal Secondary Metabolites

PubMed Central

Mefteh, Fedia B.; Daoud, Amal; Chenari Bouket, Ali; Alenezi, Faizah N.; Luptakova, Lenka; Rateb, Mostafa E.; Kadri, Adel; Gharsallah, Neji; Belbahri, Lassaad

2017-01-01

In this study, we aimed to explore and compare the composition, metabolic diversity and antimicrobial potential of endophytic fungi colonizing internal tissues of healthy and brittle leaf diseased (BLD) date palm trees (Phoenix dactylifera L.) widely cultivated in arid zones of Tunisia. A total of 52 endophytic fungi were isolated from healthy and BLD roots of date palm trees, identified based on internal transcribed spacer-rDNA sequence analysis and shown to represent 13 species belonging to five genera. About 36.8% of isolates were shared between healthy and diseased root fungal microbiomes, whereas 18.4 and 44.7% of isolates were specific to healthy and BLD root fungal microbiomes, respectively. All isolates were able to produce at least two of the screened enzymes including amylase, cellulase, chitinase, pectinase, protease, laccase and lipase. A preliminary screening of the isolates using disk diffusion method for antibacterial activity against four Gram-positive and three Gram-negative bacteria and antifungal activities against three phytopathogenic fungi indicated that healthy and BLD root fungal microbiomes displayed interesting bioactivities against examined bacteria and broad spectrum bioactivity against fungal pathogens. Some of these endophytic fungi (17 isolates) were fermented and their extracts were evaluated for antimicrobial potential against bacterial and fungal isolates. Results revealed that fungal extracts exhibited antibacterial activities and were responsible for approximately half of antifungal activities against living fungi. These results suggest a strong link between fungal bioactivities and their secondary metabolite arsenal. EtOAc extracts of Geotrichum candidum and Thielaviopsis punctulata originating from BLD microbiome gave best results against Micrococcus luteus and Bacillus subtilis with minimum inhibitory concentration (MIC, 0.78 mg/mL) and minimum bactericidal concentration (6.25 mg/mL). G. candidum gave the best result against Rhizoctonia solani with MIC 0.78 mg/mL and minimum fungicidal concentration (MFC, 6.25 mg/mL). In conclusion, using plant microbiomes subjected to biotic stresses offers new endophytes with different bioactivities than those of healthy plants. Therefore, date palm endophytic fungi represent a hidden untapped arsenal of antibacterial and broad spectrum antifungal secondary metabolites and could be considered promising source of bioactive compounds with industrial and pharmaceutical applications. PMID:28293229

Fungal Root Microbiome from Healthy and Brittle Leaf Diseased Date Palm Trees (Phoenix dactylifera L.) Reveals a Hidden Untapped Arsenal of Antibacterial and Broad Spectrum Antifungal Secondary Metabolites.

PubMed

Mefteh, Fedia B; Daoud, Amal; Chenari Bouket, Ali; Alenezi, Faizah N; Luptakova, Lenka; Rateb, Mostafa E; Kadri, Adel; Gharsallah, Neji; Belbahri, Lassaad

2017-01-01

In this study, we aimed to explore and compare the composition, metabolic diversity and antimicrobial potential of endophytic fungi colonizing internal tissues of healthy and brittle leaf diseased (BLD) date palm trees ( Phoenix dactylifera L.) widely cultivated in arid zones of Tunisia. A total of 52 endophytic fungi were isolated from healthy and BLD roots of date palm trees, identified based on internal transcribed spacer-rDNA sequence analysis and shown to represent 13 species belonging to five genera. About 36.8% of isolates were shared between healthy and diseased root fungal microbiomes, whereas 18.4 and 44.7% of isolates were specific to healthy and BLD root fungal microbiomes, respectively. All isolates were able to produce at least two of the screened enzymes including amylase, cellulase, chitinase, pectinase, protease, laccase and lipase. A preliminary screening of the isolates using disk diffusion method for antibacterial activity against four Gram-positive and three Gram-negative bacteria and antifungal activities against three phytopathogenic fungi indicated that healthy and BLD root fungal microbiomes displayed interesting bioactivities against examined bacteria and broad spectrum bioactivity against fungal pathogens. Some of these endophytic fungi (17 isolates) were fermented and their extracts were evaluated for antimicrobial potential against bacterial and fungal isolates. Results revealed that fungal extracts exhibited antibacterial activities and were responsible for approximately half of antifungal activities against living fungi. These results suggest a strong link between fungal bioactivities and their secondary metabolite arsenal. EtOAc extracts of Geotrichum candidum and Thielaviopsis punctulata originating from BLD microbiome gave best results against Micrococcus luteus and Bacillus subtilis with minimum inhibitory concentration (MIC, 0.78 mg/mL) and minimum bactericidal concentration (6.25 mg/mL). G. candidum gave the best result against Rhizoctonia solani with MIC 0.78 mg/mL and minimum fungicidal concentration (MFC, 6.25 mg/mL). In conclusion, using plant microbiomes subjected to biotic stresses offers new endophytes with different bioactivities than those of healthy plants. Therefore, date palm endophytic fungi represent a hidden untapped arsenal of antibacterial and broad spectrum antifungal secondary metabolites and could be considered promising source of bioactive compounds with industrial and pharmaceutical applications.

[Current animal feeds with antimicrobial activity].

PubMed

Drumev, D

1981-01-01

Among the growth-promoting substances and factors contributing to fodder utilization in growing farm animals, also called nutritive, ergotropic means, the antibiotics and some synthetic chemotherapeutics have acquired special importance. To avoid the hazardous effect in humans consuming products of animal origin there should be no residual amounts of these stimulating agents in such products. That is why it has been assumed in a number of countries to use for the same purpose only nutritive means that are not applied as therapeutic agents. Such means should neither induce resistence to antibiotics and chemotherapeutics in microorganism nor should they be resorbed by the alimentary tract (or resorption should be negligible) or they are rapidly eliminated from the animal body, leaving no residual amounts. They should likewise act chiefly against gram-positive organisms, inducing no allergic reactions in the animals. Described are the following nutritive antibiotics: flavophospholipol (bambermycin, menomycin--flavomycin, producing a nutritive effect also in ruminants with a developed forestomach, and rebuilds sensitivity in antibiotic-resistant organisms belonging to Enterobacteriaceae), avoparcin (avotan--also active in ruminants with a developed forestomach), virginiamycin (staphylomycin--escalin, stafac), zincbacitracin (bacipharmin, baciferm), grisin (kormogrisin, of a road spectrum, with an antimycotic effect, raising the fertilization rate and activating phagocitosis), vitamycin-A (vitamycin--active also at retinol deficiency, lambdamycin, nosiheptide (primofax), efrotomycin. Due consideration is given to such chemotherapeutics as nitrovin (payson, paison), carbadox (mecadox, fortigro, of a broad spectrum retained for a longer period in the body of pigs), olaquindox (bio-N-celbar--of a broad spectrum, particularly with regard to gram-negative organisms, applied at present as a therapeutic and prophylactic preparation), cyadox (with a broad sprectrum). The following polyether ionophoric antibiotics are mentioned: monensine (rumensine, elancoban), lassalocide (avatek, lasotek), slinomycin(eustin, ustin, coxistac), lonomycin (emercide), harasine. Dosage rates and other data are given characterising the respective preparations.

Autoclaving-Derived Surface Coating with In Vitro and In Vivo Antimicrobial and Antibiofilm Efficacies.

PubMed

Su, Yajuan; Zhi, Zelun; Gao, Qiang; Xie, Meihua; Yu, Meng; Lei, Bo; Li, Peng; Ma, Peter X

2017-03-01

Biomedical device-associated infections which engender severe threat to public health require feasible solutions. In this study, block copolymers consisting of antimicrobial, antifouling, and surface-tethering segments in one molecule are synthesized and grafted on polymeric substrates by a facile plasma/autoclave-assisted method. Hetero-bifunctional polyethylene glycol (PEG) with allyl and tosyl groups (APEG-OTs) is first prepared. PEGs with different molecular weights (1200 and 2400 Da) are employed. Polyhexamethylene guanidine (PHMG) which has excellent broad-spectrum antimicrobial activity and thermal/chemical stability, is conjugated with APEG-OTs to generate the block copolymer (APEG-PHMG). Allyl terminated PHMG (A-PHMG) without PEG segments is also synthesized by reacting PHMG with allyl glycidyl ether. The synthesized copolymers are thermal initiated by autoclaving and grafted on plasma pretreated silicone surface, forming permanently bonded bottlebrush-like coatings. Both A-PHMG and APEG 1200/2400 -PHMG coatings exhibit potent antimicrobial activity against gram-positive/negative bacteria and fungus, whereas APEG 1200/2400 -PHMG coatings show superior antifouling activity and long-term reusability to A-PHMG coating. APEG 2400 -PHMG coating demonstrates the most effective in vitro antibiofilm and protein/platelet-resistant properties, as well as excellent hemo/biocompatibility. Furthermore, APEG 2400 -PHMG greatly reduces the bacteria number with 5-log reduction in a rodent subcutaneous infection model. This rationally designed dual-functional antimicrobial and antifouling coating has great potential in combating biomedical devices/implant-associated infections. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Essential oils and metal ions as alternative antimicrobial agents: a focus on tea tree oil and silver.

PubMed

Low, Wan-Li; Kenward, Ken; Britland, Stephen T; Amin, Mohd Cim; Martin, Claire

2017-04-01

The increasing occurrence of hospital-acquired infections and the emerging problems posed by antibiotic-resistant microbial strains have both contributed to the escalating cost of treatment. The presence of infection at the wound site can potentially stall the healing process at the inflammatory stage, leading to the development of a chronic wound. Traditional wound treatment regimes can no longer cope with the complications posed by antibiotic-resistant strains; hence, there is a need to explore the use of alternative antimicrobial agents. Pre-antibiotic compounds, including heavy metal ions and essential oils, have been re-investigated for their potential use as effective antimicrobial agents. Essential oils have potent antimicrobial, antifungal, antiviral, anti-inflammatory, antioxidant and other beneficial therapeutic properties. Similarly, heavy metal ions have also been used as disinfecting agents because of their broad spectrum activities. Both of these alternative antimicrobials interact with many different intracellular components, thereby resulting in the disruption of vital cell functions and eventually cell death. This review will discuss the application of essential oils and heavy metal ions, particularly tea tree oil and silver ions, as alternative antimicrobial agents for the treatment of chronic, infected wounds. © 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Antimicrobial and Biophysical Properties of Surfactant Supplemented with an Antimicrobial Peptide for Treatment of Bacterial Pneumonia

PubMed Central

Veldhuizen, Edwin J. A.; Keating, Eleonora; Haagsman, Henk P.; Zuo, Yi Y.; Yamashita, Cory M.; Veldhuizen, Ruud A. W.

2015-01-01

Antibiotic-resistant bacterial infections represent an emerging health concern in clinical settings, and a lack of novel developments in the pharmaceutical pipeline is creating a “perfect storm” for multidrug-resistant bacterial infections. Antimicrobial peptides (AMPs) have been suggested as future therapeutics for these drug-resistant bacteria, since they have potent broad-spectrum activity, with little development of resistance. Due to the unique structure of the lung, bacterial pneumonia has the additional problem of delivering antimicrobials to the site of infection. One potential solution is coadministration of AMPs with exogenous surfactant, allowing for distribution of the peptides to distal airways and opening of collapsed lung regions. The objective of this study was to test various surfactant-AMP mixtures with regard to maintaining pulmonary surfactant biophysical properties and bactericidal functions. We compared the properties of four AMPs (CATH-1, CATH-2, CRAMP, and LL-37) suspended in bovine lipid-extract surfactant (BLES) by assessing surfactant-AMP mixture biophysical and antimicrobial functions. Antimicrobial activity was tested against methillicin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. All AMP/surfactant mixtures exhibited an increase of spreading compared to a BLES control. BLES+CATH-2 mixtures had no significantly different minimum surface tension versus the BLES control. Compared to the other cathelicidins, CATH-2 retained the most bactericidal activity in the presence of BLES. The BLES+CATH-2 mixture appears to be an optimal surfactant-AMP mixture based on in vitro assays. Future directions involve investigating the potential of this mixture in animal models of bacterial pneumonia. PMID:25753641

Antimicrobial and biophysical properties of surfactant supplemented with an antimicrobial peptide for treatment of bacterial pneumonia.

PubMed

Banaschewski, Brandon J H; Veldhuizen, Edwin J A; Keating, Eleonora; Haagsman, Henk P; Zuo, Yi Y; Yamashita, Cory M; Veldhuizen, Ruud A W

2015-01-01

Antibiotic-resistant bacterial infections represent an emerging health concern in clinical settings, and a lack of novel developments in the pharmaceutical pipeline is creating a "perfect storm" for multidrug-resistant bacterial infections. Antimicrobial peptides (AMPs) have been suggested as future therapeutics for these drug-resistant bacteria, since they have potent broad-spectrum activity, with little development of resistance. Due to the unique structure of the lung, bacterial pneumonia has the additional problem of delivering antimicrobials to the site of infection. One potential solution is coadministration of AMPs with exogenous surfactant, allowing for distribution of the peptides to distal airways and opening of collapsed lung regions. The objective of this study was to test various surfactant-AMP mixtures with regard to maintaining pulmonary surfactant biophysical properties and bactericidal functions. We compared the properties of four AMPs (CATH-1, CATH-2, CRAMP, and LL-37) suspended in bovine lipid-extract surfactant (BLES) by assessing surfactant-AMP mixture biophysical and antimicrobial functions. Antimicrobial activity was tested against methillicin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. All AMP/surfactant mixtures exhibited an increase of spreading compared to a BLES control. BLES+CATH-2 mixtures had no significantly different minimum surface tension versus the BLES control. Compared to the other cathelicidins, CATH-2 retained the most bactericidal activity in the presence of BLES. The BLES+CATH-2 mixture appears to be an optimal surfactant-AMP mixture based on in vitro assays. Future directions involve investigating the potential of this mixture in animal models of bacterial pneumonia. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Mechanical, material, and antimicrobial properties of acrylic bone cement impregnated with silver nanoparticles.

PubMed

Slane, Josh; Vivanco, Juan; Rose, Warren; Ploeg, Heidi-Lynn; Squire, Matthew

2015-03-01

Prosthetic joint infection is one of the most serious complications that can lead to failure of a total joint replacement. Recently, the rise of multidrug resistant bacteria has substantially reduced the efficacy of antibiotics that are typically incorporated into acrylic bone cement. Silver nanoparticles (AgNPs) are an attractive alternative to traditional antibiotics resulting from their broad-spectrum antimicrobial activity and low bacterial resistance. The purpose of this study, therefore, was to incorporate metallic silver nanoparticles into acrylic bone cement and quantify the effects on the cement's mechanical, material and antimicrobial properties. AgNPs at three loading ratios (0.25, 0.5, and 1.0% wt/wt) were incorporated into a commercial bone cement using a probe sonication technique. The resulting cements demonstrated mechanical and material properties that were not substantially different from the standard cement. Testing against Staphylococcus aureus and Staphylococcus epidermidis using Kirby-Bauer and time-kill assays demonstrated no antimicrobial activity against planktonic bacteria. In contrast, cements modified with AgNPs significantly reduced biofilm formation on the surface of the cement. These results indicate that AgNP-loaded cement is of high potential for use in primary arthroplasty where prevention of bacterial surface colonization is vital. Copyright © 2014 Elsevier B.V. All rights reserved.

Structural and biophysical characterization of an antimicrobial peptide chimera comprised of lactoferricin and lactoferrampin.

PubMed

Haney, Evan F; Nazmi, Kamran; Bolscher, Jan G M; Vogel, Hans J

2012-03-01

Lactoferricin and lactoferrampin are two antimicrobial peptides found in the N-terminal lobe of bovine lactoferrin with broad spectrum antimicrobial activity against a range of Gram-positive and Gram-negative bacteria as well as Candida albicans. A heterodimer comprised of lactoferrampin joined to a fragment of lactoferricin was recently reported in which these two peptides were joined at their C-termini through the two amino groups of a single Lys residue (Bolscher et al., 2009, Biochimie 91(1):123-132). This hybrid peptide, termed LFchimera, has significantly higher antimicrobial activity compared to the individual peptides or an equimolar mixture of the two. In this work, the underlying mechanism behind the increased antibacterial activity of LFchimera was investigated. Differential scanning calorimetry studies demonstrated that all the peptides influenced the thermotropic phase behaviour of anionic phospholipid suspensions. Calcein leakage and vesicle fusion experiments with anionic liposomes revealed that LFchimera had enhanced membrane perturbing properties compared to the individual peptides. Peptide structures were evaluated using circular dichroism and NMR spectroscopy to gain insight into the structural features of LFchimera that contribute to the increased antimicrobial activity. The NMR solution structure, determined in a miscible co-solvent mixture of chloroform, methanol and water, revealed that the Lys linkage increased the helical content in LFchimera compared to the individual peptides, but it did not fix the relative orientations of lactoferricin and lactoferrampin with respect to each other. The structure of LFchimera provides insight into the conformation of this peptide in a membranous environment and improves our understanding of its antimicrobial mechanism of action. Copyright © 2011 Elsevier B.V. All rights reserved.

Synergistic antimicrobial therapy using nanoparticles and antibiotics for the treatment of multidrug-resistant bacterial infection

NASA Astrophysics Data System (ADS)

Gupta, Akash; Saleh, Neveen M.; Das, Riddha; Landis, Ryan F.; Bigdeli, Arafeh; Motamedchaboki, Khatereh; Rosa Campos, Alexandre; Pomeroy, Kenneth; Mahmoudi, Morteza; Rotello, Vincent M.

2017-06-01

Infections caused by multidrug-resistant (MDR) bacteria pose a serious global burden of mortality, causing thousands of deaths each year. Antibiotic treatment of resistant infections further contributes to the rapidly increasing number of antibiotic-resistant species and strains. Synthetic macromolecules such as nanoparticles (NPs) exhibit broad-spectrum activity against MDR species, however lack of specificity towards bacteria relative to their mammalian hosts limits their widespread therapeutic application. Here, we demonstrate synergistic antimicrobial therapy using hydrophobically functionalized NPs and fluoroquinolone antibiotics for treatment of MDR bacterial strains. An 8-16-fold decrease in antibiotic dosage is achieved in presence of engineered NPs to combat MDR strains. This strategy demonstrates the potential of using NPs to ‘revive’ antibiotics that have been rendered ineffective due to the development of resistance by pathogenic bacteria.

Circular Bacteriocins: Biosynthesis and Mode of Action

PubMed Central

Brede, Dag A.; Nes, Ingolf F.; Diep, Dzung B.

2014-01-01

Circular bacteriocins are a group of N-to-C-terminally linked antimicrobial peptides, produced by Gram-positive bacteria of the phylum Firmicutes. Circular bacteriocins generally exhibit broad-spectrum antimicrobial activity, including against common food-borne pathogens, such as Clostridium and Listeria spp. These peptides are further known for their high pH and thermal stability, as well as for resistance to many proteolytic enzymes, properties which make this group of bacteriocins highly promising for potential industrial applications and their biosynthesis of particular interest as a possible model system for the synthesis of highly stable bioactive peptides. In this review, we summarize the current knowledge on this group of bacteriocins, with emphasis on the recent progress in understanding circular bacteriocin genetics, biosynthesis, and mode of action; in addition, we highlight the current challenges and future perspectives for the application of these peptides. PMID:25172850

Chemical composition, antimicrobial, antioxidant and cytotoxic activity of the essential oil from the leaves of Acanthopanax leucorrhizus (Oliv.) Harms.

PubMed

Hu, Haobin; Zheng, Xudong; Hu, Huaisheng

2012-09-01

The leaf essential oil of Acanthopanax leucorrhizus, a widely used medicinal plant, was obtained by hydrodistillation and analyzed by using combination of capillary GC-FID, GC-MS and RI. Fifty-nine components, representing 93.1% of the total oil, were identified in the essential oil and the main components of the oil were β-pinene (7.3%), linalool (6.5%), p-cymene (6.3%), β-elemene (3.8%), γ-terpinene (3.7%), spathulenol (3.2%) and cis-sabinene hydrate (3.1%). Furthermore, the in vitro antimicrobial, antioxidant and cytotoxic activities of the essential oil were examined. The test results showed that the essential oil exhibited a broad spectrum of anti-microbial activity against all microorganisms tested. Gram-positive bacteria were more sensitive to the oil than gram-negative bacteria and yeasts. The oil possessed moderate cytotoxicity on human tumor cells with lower IC(50) values of 25.65μg/ml (Hep G2), 28.71μg/ml (Hela), 30.15μg/ml (Bel-7402) and 37.55μg/ml (A-549). The moderate antioxidant activity of the oil was also evaluated by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical method. Copyright © 2012 Elsevier B.V. All rights reserved.

Antioxidant and antimicrobial properties of polyphenolic fractions from selected Moroccan red wines.

PubMed

Tenore, Gian Carlo; Basile, Adriana; Novellino, Ettore

2011-01-01

The present study is the first effort to a comprehensive evaluation of the antioxidant and antimicrobial activities of fractionated red wines from Morocco. The results obtained revealed that the wine samples were characterized by a higher phytochemical concentration than the same variety of wines with a different geographical origin and other more consumed red wines, confirming what was reported in a previous authors' work. The most phenolic-rich fractions were the ones containing phenolic acids and quercetin glucoronides from Syrah and Merlot wine samples while Cabernet Sauvignon exhibited the highest monomeric anthocyanin content. The antioxidant activity of wine extracts was tested by ferric reducing antioxidant power and 1,1-diphenyl-2-picrilhydrazyl assays. Samples revealed a higher reducing capacity than radical scavenging property and a good correlation between antioxidant activity and polyphenolic content values. As regards the antimicrobial properties, each fraction exhibited activity against a broad spectrum of food-borne microorganisms, revealing not only a moderate to high natural preserving capacity, but also potentially beneficial influence on human health. In consideration of the scarcity of data regarding composition and biological properties of Moroccan red wines, the present study may represent a valuable reference for wine consumers and producers. © 2011 Institute of Food Technologists®

Antimicrobial activity of honey from the stingless bee Trigona carbonaria determined by agar diffusion, agar dilution, broth microdilution and time-kill methodology.

PubMed

Boorn, K L; Khor, Y-Y; Sweetman, E; Tan, F; Heard, T A; Hammer, K A

2010-05-01

The aim of this study was to determine the spectrum of antimicrobial activity of 11 samples of stingless bee honey compared to medicinal, table and artificial honeys. Activity was assessed by agar diffusion, agar dilution, broth microdilution and time-kill viability assays. By agar dilution, minimum inhibitory concentration (MIC) ranges were 4% to >10% (w/v) for Gram-positive bacteria, 6% to >16% (w/v) for Gram-negative bacteria and 6% to >10% (w/v) for Candida spp. By broth microdilution, all organisms with the exception of Candida albicans and Candida glabrata were inhibited at 3 log for Pseudomonas aeruginosa and <1 log for C. albicans. Similar treatment with each control honey resulted in decreases of <1 log for all organisms. Stingless bee honey has broad-spectrum antibacterial activity although activity against Candida was limited. Stingless bee honey samples varied in activity and the basis for this remains to be determined. Stingless bee honey had similar activity to medicinal honey and may therefore have a role as a medicinal agent.

Spatial Distribution of Triclosan in Sediments and Water of an Urbanized Estuarine Embayment

EPA Science Inventory

Triclosan (TCS) is a broad spectrum anti-microbial compound found in many consumer and personal care products. TCS enters water bodies primarily through wastewater treatment plant (WWTP) effluent and may also be introduced by combined sewer overflows or surface water runoff. TC...

Streptococcus Mutans Photoinactivation by Combination of Short Exposure of a Broad-Spectrum Visible Light and Low Concentrations of Photosensitizers

PubMed Central

Paschoal, Marco Aurelio; Santos-Pinto, Lourdes; Lin, Meng

2014-01-01

Abstract Objective: Investigate the photodynamic antimicrobial effect by the combination of a novel noncoherent broad spectrum visible light and low concentrations of curcumin and toluidine blue over suspensions of Streptococcus mutans. Background data: Long illumination times to activate photosensitizers (PS) and the use of high concentrations of these drugs in photodynamic antimicrobial chemotherapy (PACT) are limitations of its application as an antimicrobial technology in dental practice. Materials and methods: Planktonic suspensions of S. mutans were standardized and submitted to PACT treatment at low concentrations of curcumin (C) (0.075; 0.75 and 7.5 μM) and toluidine blue (T) (0.25; 2.5 and 25 μM) exposed to 42 J/cm2 (12.2 sec; set power: 3.930 mW) of a white light (WL) (output wavelength range: 400–700 nm; beam diameter: 12 mm) (C+WL+ and T+WL+, PACT groups; incubation time, C: 60 sec; T: 5 min); isolated effect of both C (C+WL−) and T concentrations (T+WL−); effect of light source (C−WL+ and T−WL+) and suspensions neither submitted to PS nor to light-emitting diode (LED) illumination (control groups, C−WL− and T−WL−). Aliquots of each group were diluted and cultured on blood agar plates and the number of colony-forming units (CFU)/mL was recorded, transformed into log10 and analyzed by ANOVA and Tukey's test at a cutoff value at 0.05. Results: The groups submitted to PACT presented a bacterial reduction value of>5-log10 to both tested PS in comparison with control groups (p<0.05). PS or light source used alone demonstrated no antimicrobial effect on the number of viable bacterial counts. Conclusions: The combination of a novel noncoherent light at short illumination exposure time with low concentrations of studied PS achieved a lethal photoinactivation of S. mutans, and can be considered an effective antimicrobial in vitro approach for reducing the number of micro-organisms involved with the dental caries process. PMID:24552467

Streptococcus mutans photoinactivation by combination of short exposure of a broad-spectrum visible light and low concentrations of photosensitizers.

PubMed

Paschoal, Marco Aurelio; Santos-Pinto, Lourdes; Lin, Meng; Duarte, Simone

2014-03-01

Investigate the photodynamic antimicrobial effect by the combination of a novel noncoherent broad spectrum visible light and low concentrations of curcumin and toluidine blue over suspensions of Streptococcus mutans. Long illumination times to activate photosensitizers (PS) and the use of high concentrations of these drugs in photodynamic antimicrobial chemotherapy (PACT) are limitations of its application as an antimicrobial technology in dental practice. Planktonic suspensions of S. mutans were standardized and submitted to PACT treatment at low concentrations of curcumin (C) (0.075; 0.75 and 7.5 μM) and toluidine blue (T) (0.25; 2.5 and 25 μM) exposed to 42 J/cm2 (12.2 sec; set power: 3.930 mW) of a white light (WL) (output wavelength range: 400-700 nm; beam diameter: 12 mm) (C+WL+ and T+WL+, PACT groups; incubation time, C: 60 sec; T: 5 min); isolated effect of both C (C+WL-) and T concentrations (T+WL-); effect of light source (C-WL+ and T-WL+) and suspensions neither submitted to PS nor to light-emitting diode (LED) illumination (control groups, C-WL- and T-WL-). Aliquots of each group were diluted and cultured on blood agar plates and the number of colony-forming units (CFU)/mL was recorded, transformed into log10 and analyzed by ANOVA and Tukey's test at a cutoff value at 0.05. The groups submitted to PACT presented a bacterial reduction value of>5-log10 to both tested PS in comparison with control groups (p<0.05). PS or light source used alone demonstrated no antimicrobial effect on the number of viable bacterial counts. The combination of a novel noncoherent light at short illumination exposure time with low concentrations of studied PS achieved a lethal photoinactivation of S. mutans, and can be considered an effective antimicrobial in vitro approach for reducing the number of micro-organisms involved with the dental caries process.

Empiric Antibiotic Therapy of Nosocomial Bacterial Infections.

PubMed

Reddy, Pramod

2016-01-01

Broad-spectrum antibiotics are commonly used by physicians to treat various infections. The source of infection and causative organisms are not always apparent during the initial evaluation of the patient, and antibiotics are often given empirically to patients with suspected sepsis. Fear of attempting cephalosporins and carbapenems in penicillin-allergic septic patients may result in significant decrease in the spectrum of antimicrobial coverage. Empiric antibiotic therapy should sufficiently cover all the suspected pathogens, guided by the bacteriologic susceptibilities of the medical center. It is important to understand the major pharmacokinetic properties of antibacterial agents for proper use and to minimize the development of resistance. In several septic patients, negative cultures do not exclude active infection and positive cultures may not represent the actual infection. This article will review the important differences in the spectrum of commonly used antibiotics for nosocomial bacterial infections with a particular emphasis on culture-negative sepsis and colonization.

Delafloxacin: design, development and potential place in therapy.

PubMed

Candel, Francisco Javier; Peñuelas, Marina

2017-01-01

Delafloxacin (DLX) is a new fluoroquinolone pending approval, which has shown a good in vitro and in vivo activity against major pathogens associated with skin and soft tissue infections and community-acquired respiratory tract infections. DLX also shows good activity against a broad spectrum of microorganisms, including those resistant to other fluoroquinolones, as methicillin-resistant Staphylococcus aureus . Its pharmacokinetic properties and excellent activity in acidic environments make DLX an alternative in the treatment of these and other infections. In this manuscript, a detailed analysis of this new fluoroquinolone is performed, from its chemical structure to its in vivo activity in recently published clinical trials. Its possible place in the current antimicrobial outlook and in other infectious models is also discussed.

Delafloxacin: design, development and potential place in therapy

PubMed Central

Candel, Francisco Javier; Peñuelas, Marina

2017-01-01

Delafloxacin (DLX) is a new fluoroquinolone pending approval, which has shown a good in vitro and in vivo activity against major pathogens associated with skin and soft tissue infections and community-acquired respiratory tract infections. DLX also shows good activity against a broad spectrum of microorganisms, including those resistant to other fluoroquinolones, as methicillin-resistant Staphylococcus aureus. Its pharmacokinetic properties and excellent activity in acidic environments make DLX an alternative in the treatment of these and other infections. In this manuscript, a detailed analysis of this new fluoroquinolone is performed, from its chemical structure to its in vivo activity in recently published clinical trials. Its possible place in the current antimicrobial outlook and in other infectious models is also discussed. PMID:28356714

Review on the Antimicrobial Properties of Carbon Nanostructures

PubMed Central

Al-Jumaili, Ahmed; Alancherry, Surjith; Bazaka, Kateryna

2017-01-01

Swift developments in nanotechnology have prominently encouraged innovative discoveries across many fields. Carbon-based nanomaterials have emerged as promising platforms for a broad range of applications due to their unique mechanical, electronic, and biological properties. Carbon nanostructures (CNSs) such as fullerene, carbon nanotubes (CNTs), graphene and diamond-like carbon (DLC) have been demonstrated to have potent broad-spectrum antibacterial activities toward pathogens. In order to ensure the safe and effective integration of these structures as antibacterial agents into biomaterials, the specific mechanisms that govern the antibacterial activity of CNSs need to be understood, yet it is challenging to decouple individual and synergistic contributions of physical, chemical and electrical effects of CNSs on cells. In this article, recent progress in this area is reviewed, with a focus on the interaction between different families of carbon nanostructures and microorganisms to evaluate their bactericidal performance. PMID:28892011

Evaluation of the Antimicrobial Activity of Endophytic Bacterial Populations From Chinese Traditional Medicinal Plant Licorice and Characterization of the Bioactive Secondary Metabolites Produced by Bacillus atrophaeus Against Verticillium dahliae.

PubMed

Mohamad, Osama A A; Li, Li; Ma, Jin-Biao; Hatab, Shaimaa; Xu, Lin; Guo, Jian-Wei; Rasulov, Bakhtiyor A; Liu, Yong-Hong; Hedlund, Brian P; Li, Wen-Jun

2018-01-01

Endophytic bacteria associated with medicinal plants possess unique strategies that enhance growth and suvival of host plants, many of which are mediated by distinctive secondary metabolites. These bacteria and their secondary metabolites are important subjects for both basic and applied research aimed at sustainable agriculture. In the present study, 114 endophytic strains isolated from the wild ethnomedicinal plant Glycyrrhiza uralensis (licorice) were screened for their in vitro antimicrobial activities against common fungal pathogens of tomato ( Fusarium oxysporum f. sp., Fulvia fulva , Alternaria solani ), cotton ( Fusarium oxysporum f. sp. Vesinfectum, Verticillium dahliae ), pomegranite ( Ceratocystis fimbriata ), Cymbidinium ( Colletotrichum gloeosporioides ), and Tsao-ko ( Pestalotiopsis microspora and Fusarium graminearum ) and the common bacteria Staphylococcus aureus , Bacillus cereus , Salmonella enteritidis , and Escherichia coli . Several Bacillus strains, particularly Bacillus atrophaeus and Bacillus mojavensis , had a broad spectrum of antifungal and antibacterial activity. A total of 16 strains, selected based on broad antimicrobial activity, were shown to contain at least one putative secondary metabolite-encoding gene (i.e., polyketide synthase or non-ribosomal peptide synthetase) and/or one lytic enzyme (i.e., protease, cellulase, lipase, chitinase), which may be important mediators of antagonistic activity against pathogens. Five strains, representing Bacillus atrophaeus and Bacillus mojavensis , were selected for plant growth chamber experiments based on strong in vitro antifungal activities. All five strains significantly reduced disease severity in Arabidopsis thaliana plants challenged with V. dahlia infection. Gas-chromatography/mass-spectrometry analysis of cell-free extracts of Bacillus atrophaeus strain XEGI50 showed that at least 13 compounds were produced only during co-cultivation with V. dahlia , including putative compounds known to have antimicrobial activity, such as 1,2-benzenedicarboxylic acid, bis (2-methylpropyl) ester; 9,12-octadecadienoic acid (Z,Z)-, methyl ester; 9-octadecenoic acid, methyl ester, (E)-; and decanedioic acid, bis(2-ethylhexyl) ester. To our knowledge, this study is the first to report that bacteria isolated from G. uralensis have biocontrol abilities. Our findings provide new insights into the antimicrobial activities of natural endophytes, particularly B. atrophaeus , and suggest this species may a promising candidate as a biocontrol agent to confer resistance to Verticillium wilt disease and other phytopathogens in cotton and other crops.

Examination of antimicrobial activity of selected non-antibiotic medicinal preparations.

PubMed

Kruszewska, Hanna; Zareba, Tomasz; Tyski, Stefan

2012-01-01

The aim of this study was to detect and characterize the antimicrobial activity of non-antibiotic drugs, selected from the pharmaceutical products analyzed during the state control performed in National Medicines Institute, Warszawa, Poland. In 2010, over 90 pharmaceutical preparations have been randomly chosen from different groups of drugs. The surveillance study was performed on standard ATCC microbial strains used for drug control: S. aureus, E. coli, P. aeruginosa and C. albicans. It was shown that the drugs listed below inhibited growth of at least one of the examined strains: Arketis 20 mg tab. (paroxetine), Buvasodil 150 mg tab. (buflomedile), Halidor 100 mg tab. (bencyclane), Hydroxyzinum espefa 25 mg tab. (hydroxyzine), Norifaz 35 mg tab. (risedronate), Strattera 60 mg cap. (atomoxetine), Tamiflu 75 mg tab. (oseltamivir), Valpro-ratiopharm Chrono 300 mg tab. with longer dissolution (valproate), Vetminth oral paste 24 g+3 g/100 mL (niclozamide, oxybendazol). Strattera cap. showed broad activity spectrum. It inhibited growth of all examined strains (MIC of active substance -- atomoxetine ranged between 2.6-13 mg/mL).

Chemical composition and antibacterial activity of essential oil from fruit of Micromelum integerrimum (Buch.-Ham. ex DC.) Wight & Arn. ex M. Roem.

PubMed

Kotoky, Rumi; Bordoloi, Manobjyoti; Yadav, Archana; Tamuli, Kashyap J; Saikia, Surovi; Dutta, Partha P; Khound, Prodip P; Saikia, Siddhartha P

2018-06-13

The essential oil extracted from fruit of Micromelum integrrimum were evaluated through gas chromatography and gas chromatography-mass spectroscopy. 52 compounds were identified from the fruit oil representing 99.98% of the oil. The major components of the total fruit oil are monoterpene hydrocarbons (72.23%), oxygenated monoterpenes (14.78%) and sesquiterpene (11.54%) which were predominated by terpinolene (32.21%), α-pinene (17.24%), β-pinene (17.24%), and camphene (4.05%). Moreover, other components that present in 1.45% were aromatic compounds, fatty acid, etc. The essential oil exhibited broad spectrum antimicrobial activity which is concentration dependent and 100 μL of the fruit oil showed the inhibition zones ranging from 7-16 mm. Fruit oil exhibited strong inhibition activity compared to standard anti-bacterial drug neomycin B (22 mm) against Bacillus subtilis MTCC 441 and Bacillus spizizenii ATCC 6633. This is the first hand report on the chemical profiles and promising anti-microbial activity of Micromelum integrrimum fruit essential oil towards Basillus Sp.

Marine Fish Proteins and Peptides for Cosmeceuticals: A Review

PubMed Central

Venkatesan, Jayachandran; Anil, Sukumaran; Kim, Se-Kwon; Shim, Min Suk

2017-01-01

Marine fish provide a rich source of bioactive compounds such as proteins and peptides. The bioactive proteins and peptides derived from marine fish have gained enormous interest in nutraceutical, pharmaceutical, and cosmeceutical industries due to their broad spectrum of bioactivities, including antioxidant, antimicrobial, and anti-aging activities. Recently, the development of cosmeceuticals using marine fish-derived proteins and peptides obtained from chemical or enzymatical hydrolysis of fish processing by-products has increased rapidly owing to their activities in antioxidation and tissue regeneration. Marine fish-derived collagen has been utilized for the development of cosmeceutical products due to its abilities in skin repair and tissue regeneration. Marine fish-derived peptides have also been utilized for various cosmeceutical applications due to their antioxidant, antimicrobial, and matrix metalloproteinase inhibitory activities. In addition, marine fish-derived proteins and hydrolysates demonstrated efficient anti-photoaging activity. The present review highlights and presents an overview of the current status of the isolation and applications of marine fish-derived proteins and peptides. This review also demonstrates that marine fish-derived proteins and peptides have high potential for biocompatible and effective cosmeceuticals. PMID:28524092

Influence of solid state fermentation by Trichoderma spp. on solubility, phenolic content, antioxidant, and antimicrobial activities of commercial turmeric.

PubMed

Mohamed, Saleh A; Saleh, Rashad M; Kabli, Saleh A; Al-Garni, Saleh M

2016-05-01

The influence of solid state fermentation (SSF) by Trichoderma spp. on the solubility, total phenolic content, antioxidant, and antibacterial activities of turmeric was determined and compared with unfermented turmeric. The solubility of turmeric was monitored by increase in its phenolic content. The total phenolic content of turmeric extracted by 80% methanol and water after SSF by six species of Trichoderma spp. increased significantly from 2.5 to 11.3-23.3 and from 0.5 to 13.5-20.4 GAE/g DW, respectively. The antioxidant activities of fermented turmeric were enhanced using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzo-thiazoline-6-sulfonic acid) (ABTS), and ferric ion-reducing antioxidant power (FRAP) assays. The antibacterial activity of fermented turmeric against human-pathogenic bacteria Escherichia coli, Streptococcus agalactiae, Staphylococcus aureus, Entreococcus faecalis, Methicillin-Resistant S. aureus, Klebsiella pneumonia, and Pseudomonas aeruginosae showed a broad spectrum inhibitory effect. In conclusion, the results indicated the potentials of using fermented turmeric as natural antioxidant and antimicrobial material for food applications.

Biofouling-resistant ceragenin-modified materials and structures for water treatment

DOEpatents

Hibbs, Michael; Altman, Susan J.; Jones, Howland D. T.; Savage, Paul B.

2013-09-10

This invention relates to methods for chemically grafting and attaching ceragenin molecules to polymer substrates; methods for synthesizing ceragenin-containing copolymers; methods for making ceragenin-modified water treatment membranes and spacers; and methods of treating contaminated water using ceragenin-modified treatment membranes and spacers. Ceragenins are synthetically produced antimicrobial peptide mimics that display broad-spectrum bactericidal activity. Alkene-functionalized ceragenins (e.g., acrylamide-functionalized ceragenins) can be attached to polyamide reverse osmosis membranes using amine-linking, amide-linking, UV-grafting, or silane-coating methods. In addition, silane-functionalized ceragenins can be directly attached to polymer surfaces that have free hydroxyls.

Phytochemicals and bioactivities of Anemone raddeana Regel: a review.

PubMed

Sun, Yong-Xu; Liu, Ji-Cheng; Liu, Da-You

2011-11-01

Anemone raddeana, usually called as'"Toujian Liang" in China, is an Anemone herb belonging to the Ranunculaceae family. Until now there are in total 67 of chemical components identified including triterpenoids, steroids, lactones, fats and oils, saccharide and alkaloids. A broad spectrum of pharmacological activity of A. raddeana compounds have been reported, such as antitumor, antimicrobial, anti-inflammatory, sedative and analgesic activites, as well as anti-convulsant and anti-histamine effects. In view of this, we initiated this short review to present the phytochemical and pharmacological profile of A. raddeana to support future studies in this discipline.

The Urinary Antibiotic 5-Nitro-8-Hydroxyquinoline (Nitroxoline) Reduces the Formation and Induces the Dispersal of Pseudomonas aeruginosa Biofilms by Chelation of Iron and Zinc

PubMed Central

Klinger, M.; Hermann, B.; Sachse, S.; Nietzsche, S.; Makarewicz, O.; Keller, P. M.; Pfister, W.; Straube, E.

2012-01-01

Since cations have been reported as essential regulators of biofilm, we investigated the potential of the broad-spectrum antimicrobial and cation-chelator nitroxoline as an antibiofilm agent. Biofilm mass synthesis was reduced by up to 80% at sub-MIC nitroxoline concentrations in Pseudomonas aeruginosa, and structures formed were reticulate rather than compact. In preformed biofilms, viable cell counts were reduced by 4 logs at therapeutic concentrations. Complexation of iron and zinc was demonstrated to underlie nitroxoline's potent antibiofilm activity. PMID:22926564

Identification of a novel endophytic Bacillus sp. from Capsicum annuum with highly efficient and broad spectrum plant probiotic effect.

PubMed

Jasim, B; Mathew, J; Radhakrishnan, E K

2016-10-01

The study mainly aimed the isolation and characterization of plant probiotic endophytic bacteria from Capsicum annuum to explore its multipotent agricultural applications. Endophytic bacteria were isolated from the surface sterilized fruit tissue. The isolates were then subjected to PCR-based screening for the presence of potential biosynthetic gene clusters. The PCR positive isolate was then analysed for its inhibitory effect towards fungal and bacterial pathogens. The compounds responsible for the antimicrobial activity was purified from large scale culture and subjected to identification by LC-MS/MS. The ability of the selected isolate in plant growth enhancement was also done using Vigna radiata seedlings. In this study, an endophytic bacterium isolated from C. annuum was found to have the phenotypic and genetic basis for broad antimicrobial property. PCR-based sequence analysis has resulted in the identification of nonribosomal peptide synthases, PKS Type I, Iturin, surfactin, DAPG and gacA genes in the selected isolate CaB 5. The bioactivity-guided fractionation using column and HPLC purification of active fraction followed by LC-MS/MS analysis has proved the presence of surfactin derivatives (M+H(+) - 1008 & 1036) and iturin (M+H(+) - 1058) as the basis of antimicrobial activity of CaB 5. The isolate was identified as a novel Bacillus sp. because of its low (76%) identity to the reported sequences. Endophytes are considered to have the genetic basis for a diverse array of bioactive metabolites which can have significant applications in both pharmaceutical industry and agriculture. The identification of CaB 5 with broad bioactivity and excellent plant growth enhancement on taxonomically distinct plant species as explained in current study and our previous reports highlights its plant probiotic applicability. This proves the potential of the isolate obtained in the study to be an excellent plant probiotic. © 2016 The Society for Applied Microbiology.

Synthesis and biological evaluation of coumarin derivatives containing imidazole skeleton as potential antibacterial agents.

PubMed

Hu, Yang; Shen, Yufeng; Wu, Xiaohu; Tu, Xiao; Wang, Gao-Xue

2018-01-01

Emergence of multidrug-resistant bacteria causes an urgent need for new generation of antibiotics, which may have a different mechanism of inhibition or killing action from the existing. Here, we report on the design, synthesis, and biological evaluation of thirty-nine coumarin derivatives in order to solve the antibacterial resistance by targeting at the inhibition of biosynthesis pathway of fatty acids. Their antibacterial activities against Escherichia coli, Staphylococcus aureus, Streptococcus agalactiae, and Flavobacterium cloumnare are tested and action mechanism against the key enzyme in bacterial fatty acid synthesis pathway are studied. The results show that compounds 13 and 18 have potent and broad spectrum antimicrobial activity. In addition, 9, 14 and 19 show eminent antimicrobial efficacy toward S. aureus, S. agalactiae, and F. cloumnare. Mechanistically, coumarin derivatives display the antibacterial activity via the control of FabI and FabK function. The structure-activity relationship analysis indicate that the length of linker and imidazole substitute group could significantly influence the antimicrobial activity, as well as the inhibitory activity against FabI and FabK. The structural optimization analysis of coumarin suggest that derivatives 9, 13, 14, 18 and 19 could be a viable way of preventing and controlling bacteria and considered as promising lead compounds for the development of commercial drugs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Could chloramphenicol be used against ESKAPE pathogens? A review of in vitro data in the literature from the 21st century.

PubMed

Čivljak, Rok; Giannella, Maddalena; Di Bella, Stefano; Petrosillo, Nicola

2014-02-01

The widespread use of antibiotics has been associated with the emergence of antimicrobial resistance among bacteria. 'ESKAPE' (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acintobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) pathogens play a major role in the rapidly changing scenario of antimicrobial resistance in the 21st century. Chloramphenicol is a broad spectrum antibiotic that was abandoned in developed countries due to its association with fatal aplastic anemia. However, it is still widely used in the developing world. In light of the emerging problem of multi-drug resistant pathogens, its role should be reassessed. Our paper reviews in vitro data on the activity of chloramphenicol against ESKAPE pathogens. Susceptibility patterns for Gram-positives were good, although less favorable for Gram-negatives. However, in combination with colistin, chloramphenicol was found to have synergistic activity. The risk-benefit related to chloramphenicol toxicity has not been analyzed. Therefore, extra precautions should be taken when prescribing this agent.

Membrane perturbation activity of cationic phenylene ethynylene oligomers and polymers: selectivity against model bacterial and mammalian membranes.

PubMed

Wang, Ying; Tang, Yanli; Zhou, Zhijun; Ji, Eunkyung; Lopez, Gabriel P; Chi, Eva Y; Schanze, Kirk S; Whitten, David G

2010-08-03

Poly(phenylene ethyneylene) (PPE)-based cationic conjugated polyelectrolytes (CPEs) and cationic phenylene ethynylene oligomers (OPEs) exhibit broad-spectrum antimicrobial activity, and their main target is believed to be the cell membrane. To understand better how these antimicrobial molecules interact with membranes, a series of PPE-based CPEs and OPEs with different side chains were studied. Large unilamellar vesicles with lipid compositions mimicking those of mammalian or bacterial membranes were used as model membranes. Among the CPEs and OPEs tested, the anionic CPE, PPE-SO(3)(2-) and the smallest cationic OPE-1 are inactive against all vesicles. Other cationic CPEs and OPEs show significant membrane perturbation ability against bacterial membrane mimics but are inactive against a mammalian cell membrane mimic with the exception of PPE-DABCO and two end-only-functionalized OPEs, which also disrupted a mammalian cell membrane mimic. The results suggest that the phospholipid composition of vesicles dominates the interaction of CPE and OPE with lipid membranes.

Antimicrobial activity of Manuka honey against antibiotic-resistant strains of the cell wall-free bacteria Ureaplasma parvum and Ureaplasma urealyticum.

PubMed

Hillitt, K L; Jenkins, R E; Spiller, O B; Beeton, M L

2017-03-01

The susceptibility of the cell wall-free bacterial pathogens Ureaplasma spp. to Manuka honey was examined. The minimum inhibitory concentration (MIC) of Manuka honey for four Ureaplasma urealyticum and four Ureaplasma parvum isolates was determined. Sensitivity to honey was also compared to clinical isolates with resistance to tetracycline, macrolide and fluoroquinolone antibiotics. Finally step-wise resistance training was utilized in an attempt to induce increased tolerance to honey. The MIC was dependent on the initial bacterial load with 7·5 and 18·0% w/v honey required to inhibit U. urealyticum at 1 and 10 6 colour changing units (CCU), respectively, and 4·8 and 15·3% w/v required to inhibit U. parvum at 1 and 10 6  CCU respectively. MIC values were consistently lower for U. parvum compared with U. urealyticum. Antimicrobial activity was seen against tetracycline-resistant, erythromycin-resistant and ciprofloxacin-resistant isolates at 10 5  CCU. No resistance to honey was observed with 50 consecutive challenges at increasing concentrations of honey. This is the first report of the antimicrobial activity of Manuka honey against a cell wall-free bacterial pathogen. The antimicrobial activity was retained against antibiotic-resistant strains and it was not possible to generate resistant mutants. Manuka honey is known to have a broad spectrum of antimicrobial activity, with the bacterial cell wall being suggested as a predominant site of action. This study has demonstrated that Manuka honey has activity against Ureaplasma spp., a genus of cell wall-free bacteria which are intrinsically resistant to many available antibiotics making treatment inherently difficult. This is the first report of the antimicrobial activity of Manuka honey against a bacterial pathogen, in the absence of a cell well and opens scope for the use of components of Manuka honey as a therapeutic among Ureaplasma infections. © 2016 The Society for Applied Microbiology.

Bactericidal and antibiofilm activity of bactenecin-derivative peptides against the food-pathogen Listeria monocytogenes: New perspectives for food processing industry.

PubMed

Palmieri, Gianna; Balestrieri, Marco; Capuano, Federico; Proroga, Yolande T R; Pomilio, Francesco; Centorame, Patrizia; Riccio, Alessia; Marrone, Raffaele; Anastasio, Aniello

2018-08-20

Antimicrobial peptides have received great attention for their potential benefits to extend the shelf-life of food-products. Innate defense regulator peptide-1018 (IDR-1018) represents a promising candidate for such applications, due to its broad-spectrum antimicrobial activity, although food-isolated pathogens have been poorly investigated. Herein, we describe the design and the structural-functional characterization of a new 1018-derivative peptide named 1018-K6, in which the alanine in position 6 was replaced with a lysine. Spectroscopic analysis revealed a noticeable switch from β-sheet to helical conformations of 1018-K6 respect to IDR-1018, with a faster folding kinetic and increased structural stability. Moreover, 1018-K6 evidenced a significant antibiofilm/bactericidal efficiency specifically against Listeria monocytogenes isolates from food-products and food-processing environments, belonging to serotype 4b involved in the majority of human-listeriosis cases, with EC 50 values two- five-fold lower than those measured for IDR-1018. Therefore, a single amino-acid substitution in IDR-1018 sequence produced severe changes in peptide conformation and antimicrobial performances. Published by Elsevier B.V.

Cysteamine, an Endogenous Aminothiol, and Cystamine, the Disulfide Product of Oxidation, Increase Pseudomonas aeruginosa Sensitivity to Reactive Oxygen and Nitrogen Species and Potentiate Therapeutic Antibiotics against Bacterial Infection

PubMed Central

Smith, Daniel; Kowalczuk, Aleksandra; Robertson, Jennifer; Lovie, Emma; Perenyi, Peter; Cole, Michelle; Doumith, Michel; Hill, Robert L. R.; Hopkins, Katie L.; Woodford, Neil; O'Neil, Deborah A.

2018-01-01

ABSTRACT Cysteamine is an endogenous aminothiol produced in mammalian cells as a consequence of coenzyme A metabolism through the activity of the vanin family of pantetheinase ectoenzymes. It is known to have a biological role in oxidative stress, inflammation, and cell migration. There have been several reports demonstrating anti-infective properties targeting viruses, bacteria, and even the malarial parasite. We and others have previously described broad-spectrum antimicrobial and antibiofilm activities of cysteamine. Here, we go further to demonstrate redox-dependent mechanisms of action for the compound and how its antimicrobial effects are, at least in part, due to undermining bacterial defenses against oxidative and nitrosative challenges. We demonstrate the therapeutic potentiation of antibiotic therapy against Pseudomonas aeruginosa in mouse models of infection. We also demonstrate potentiation of many different classes of antibiotics against a selection of priority antibiotic-resistant pathogens, including colistin (often considered an antibiotic of last resort), and we discuss how this endogenous antimicrobial component of innate immunity has a role in infectious disease that is beginning to be explored and is not yet fully understood. PMID:29581193

Interaction of MreB-derived antimicrobial peptides with membranes.

PubMed

Saikia, Karabi; Chaudhary, Nitin

2018-03-25

Antimicrobial peptides are critical components of defense systems in living forms. The activity is conferred largely by the selective membrane-permeabilizing ability. In our earlier work, we derived potent antimicrobial peptides from the 9-residue long, N-terminal amphipathic helix of E. coli MreB protein. The peptides display broad-spectrum activity, killing not only Gram-positive and Gram-negative bacteria but opportunistic fungus, Candida albicans as well. These results proved that membrane-binding stretches of bacterial proteins could turn out to be self-harming when applied from outside. Here, we studied the membrane-binding and membrane-perturbing potential of these peptides. Steady-state tryptophan fluorescence studies with tryptophan extended peptides, WMreB 1-9 and its N-terminal acetylated analog, Ac-WMreB 1-9 show preferential binding to negatively-charged liposomes. Both the peptides cause permeabilization of E. coli inner and outer-membranes. Tryptophan-lacking peptides, though permeabilize the outer-membrane efficiently, little permeabilization of the inner-membrane is observed. These data attest membrane-destabilization as the mechanism of rapid bacterial killing. This study is expected to motivate the research in identifying microbes' self-sequences to combat them. Copyright © 2018 Elsevier Inc. All rights reserved.

Transplantation of periodontal ligament cell sheets expressing human β-defensin-3 promotes anti-inflammation in a canine model of periodontitis

PubMed Central

Zhu, Minwen; Miao, Bo; Zhu, Jianhua; Wang, Haiyan; Zhou, Zengtong

2017-01-01

Periodontitis is a chronic oral inflammatory disease caused by microorganisms. Human β-defensin-3 (HBD-3) is an endogenous antimicrobial peptide that inhibits a broad spectrum of microorganisms. Cell sheet technology has been widely applied in tissue and organ reconstructions. In the current study, it was aimed to investigate the anti-inflammatory effect of periodontal tissue engineered by HBD-3 gene-modified periodontal ligament cell (PDLC) sheets, and to identify a suitable method of promoting the regeneration of periodontal tissues. Western blot analysis and antimicrobial tests were used to confirm the expression of HBD-3. The effect of the cell sheets on anti-inflammatory activity and bone remodeling in a dog model of periodontitis was demonstrated by immunohistochemistry. The results demonstrated that the transfected PDLCs stably expressed HBD-3. Periodontal pathogens were susceptible to the antimicrobial activity of the cell sheets. In addition, the cell sheets relieved the bone resorption caused by inflammation in the in vivo model. HBD-3 may potentially be applied in the treatment of periodontitis and may function as osteogenic promoter via its anti-inflammatory effect. PMID:28944821

Transplantation of periodontal ligament cell sheets expressing human β‑defensin‑3 promotes anti‑inflammation in a canine model of periodontitis.

PubMed

Zhu, Minwen; Miao, Bo; Zhu, Jianhua; Wang, Haiyan; Zhou, Zengtong

2017-11-01

Periodontitis is a chronic oral inflammatory disease caused by microorganisms. Human β‑defensin‑3 (HBD‑3) is an endogenous antimicrobial peptide that inhibits a broad spectrum of microorganisms. Cell sheet technology has been widely applied in tissue and organ reconstructions. In the current study, it was aimed to investigate the anti‑inflammatory effect of periodontal tissue engineered by HBD‑3 gene‑modified periodontal ligament cell (PDLC) sheets, and to identify a suitable method of promoting the regeneration of periodontal tissues. Western blot analysis and antimicrobial tests were used to confirm the expression of HBD‑3. The effect of the cell sheets on anti‑inflammatory activity and bone remodeling in a dog model of periodontitis was demonstrated by immunohistochemistry. The results demonstrated that the transfected PDLCs stably expressed HBD‑3. Periodontal pathogens were susceptible to the antimicrobial activity of the cell sheets. In addition, the cell sheets relieved the bone resorption caused by inflammation in the in vivo model. HBD‑3 may potentially be applied in the treatment of periodontitis and may function as osteogenic promoter via its anti‑inflammatory effect.

Expression of Caenorhabditis elegans antimicrobial peptide NLP-31 in Escherichia coli

NASA Astrophysics Data System (ADS)

Lim, Mei-Perng; Nathan, Sheila

2014-09-01

Burkholderia pseudomallei is the causative agent of melioidosis, a fulminant disease endemic in Southeast Asia and Northern Australia. The standardized form of therapy is antibiotics treatment; however, the bacterium has become increasingly resistant to these antibiotics. This has spurred the need to search for alternative therapeutic agents. Antimicrobial peptides (AMPs) are small proteins that possess broad-spectrum antimicrobial activity. In a previous study, the nematode Caenorhabditis elegans was infected by B. pseudomallei and a whole animal transcriptome analysis identified a number of AMP-encoded genes which were induced significantly in the infected worms. One of the AMPs identified is NLP-31 and to date, there are no reports of anti-B. pseudomallei activity demonstrated by NLP-31. To produce NLP-31 protein for future studies, the gene encoding for NLP-31 was cloned into the pET32b expression vector and transformed into Escherichia coli BL21(DE3). Protein expression was induced with 1 mM IPTG for 20 hours at 20°C and recombinant NLP-31 was detected in the soluble fraction. Taken together, a simple optimized heterologous production of AMPs in an E. coli expression system has been successfully developed.

Antimicrobial Peptides as Mediators of Innate Immunity in Teleosts

PubMed Central

Katzenback, Barbara A.

2015-01-01

Antimicrobial peptides (AMPs) have been identified throughout the metazoa suggesting their evolutionarily conserved nature and their presence in teleosts is no exception. AMPs are short (18–46 amino acids), usually cationic, amphipathic peptides. While AMPs are diverse in amino acid sequence, with no two AMPs being identical, they collectively appear to have conserved functions in the innate immunity of animals towards the pathogens they encounter in their environment. Fish AMPs are upregulated in response to pathogens and appear to have direct broad-spectrum antimicrobial activity towards both human and fish pathogens. However, an emerging role for AMPs as immunomodulatory molecules has become apparent—the ability of AMPs to activate the innate immune system sheds light onto the multifaceted capacity of these small peptides to combat pathogens through direct and indirect means. Herein, this review focuses on the role of teleost AMPs as modulators of the innate immune system and their regulation in response to pathogens or other exogenous molecules. The capacity to regulate AMP expression by exogenous factors may prove useful in modulating AMP expression in fish to prevent disease, particularly in aquaculture settings where crowded conditions and environmental stress pre-dispose these fish to infection. PMID:26426065

A Systematic Review of the Definitions, Determinants, and Clinical Outcomes of Antimicrobial De-escalation in the Intensive Care Unit.

PubMed

Tabah, Alexis; Cotta, Menino Osbert; Garnacho-Montero, Jose; Schouten, Jeroen; Roberts, Jason A; Lipman, Jeffrey; Tacey, Mark; Timsit, Jean-François; Leone, Marc; Zahar, Jean Ralph; De Waele, Jan J

2016-04-15

Antimicrobial de-escalation (ADE) is a strategy to reduce the spectrum of antimicrobials and aims to prevent the emergence of bacterial resistance. We present a systematic review describing the definitions, determinants and outcomes associated with ADE. We included 2 randomized controlled trials and 12 cohort studies. There was considerable variability in the definition of ADE. It was more frequently performed in patients with broad-spectrum and/or appropriate antimicrobial therapy (P= .05 to .002), when more agents were used (P= .002), and in the absence of multidrug-resistant pathogens (P< .05). Where investigated, lower or improving severity scores were consistently associated with ADE (P= .04 to <.001). The pooled effect of ADE on mortality is protective (relative risk, 0.68; 95% confidence interval, .52-.88). Because the determinants of ADE are markers of clinical improvement and/or of lower risk of treatment failure this effect on mortality cannot be retained as evidence. None of the studies were designed to investigate the effect of ADE on antimicrobial resistance. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Broad-spectrum agents for flaviviral infections: dengue, Zika and beyond.

PubMed

Boldescu, Veaceslav; Behnam, Mira A M; Vasilakis, Nikos; Klein, Christian D

2017-08-01

Infections with flaviviruses, such as dengue, West Nile virus and the recently re-emerging Zika virus, are an increasing and probably lasting global risk. This Review summarizes and comments on the opportunities for broad-spectrum agents that are active against multiple flaviviruses. Broad-spectrum activity is particularly desirable to prepare for the next flaviviral epidemic, which could emerge from as-yet unknown or neglected viruses. Potential molecular targets for broad-spectrum antiflaviviral compounds include viral proteins, such as the viral protease or polymerase, and host targets that are exploited by these viruses during entry and replication, including α-glucosidase and proteins involved in nucleoside biosynthesis. Numerous compounds with broad-spectrum antiviral activity have already been identified by target-specific or phenotypic assays. For other compounds, broad-spectrum activity can be anticipated because of their mode of action and molecular targets.

2-Amino-1,3,4-thiadiazole as a potential scaffold for promising antimicrobial agents.

PubMed

Serban, Georgeta; Stanasel, Oana; Serban, Eugenia; Bota, Sanda

2018-01-01

Pathogenic microorganisms are causative agents for different types of serious and even lethal infectious diseases. Despite advancements in medication, bacterial and fungal infections continue to be a growing problem in health care. As more and more bacteria become resistant to antibiotics used in therapy and an increasing number of invasive fungal species become resistant to current antifungal medications, there is considerable interest in the development of new compounds with antimicrobial activity. The compounds containing a heterocyclic ring play an important role among organic compounds with biological activity used as drugs in human and veterinary medicine or as insecticides and pesticides in agriculture. Thiadiazoles belong to the classes of nitrogen-sulfur heterocycles with extensive application as structural units of biologically active molecules and as useful intermediates in medicinal chemistry. The potency of the thiadiazole nucleus is demonstrated by the drugs currently used. 1,3,4-Thiadiazoles and some of their derivatives are extensively studied because of their broad spectrum of pharmacological activities. The aim of this review was to highlight the main antimicrobial properties exhibited by derivatives possessing 2-amino-1,3,4-thiadiazole moiety. Many of the reported 2-amino-1,3,4-thiadiazole derivatives can be considered as lead compounds for drug synthesis, and several of them have demonstrated higher antimicrobial activity in comparison to standard drugs. Furthermore, taking into account the reactivity of the amine group in the derivatization process, 2-amino-1,3,4-thiadiazole moiety may be a good scaffold for future pharmacologically active 1,3,4-thiadiazole derivatives.

Antimicrobial resistance and prudent drug use for Streptococcus suis.

PubMed

Varela, Norma P; Gadbois, Pierre; Thibault, Claude; Gottschalk, Marcelo; Dick, Paul; Wilson, Jeff

2013-06-01

This paper reviews information on antimicrobial resistance patterns and prudent use of antimicrobials to reduce the impact and spread of resistant Streptococcus suis strains. S. suis is an important pathogen in swine, which can cause significant economic loss. Prudent use of antimicrobials for S. suis is essential to preserve the therapeutic efficacy of broad-spectrum antimicrobials and to minimize selection of resistant S. suis strains. Resistance of S. suis to antimicrobials commonly used in swine, including lincosamides, macrolides, sulphonamides, and tetracycline, has been documented worldwide, with resistance in up to 85% of strains. Among antimicrobials examined, resistance of S. suis has been demonstrated to be relatively low for penicillin (0-27%), ampicillin (0.6-23%), and ceftiofur (0-23%). For penicillin, this result may be due in part to the unique mechanism by which resistance is acquired through modifications in the structure of penicillin-binding proteins. Recommendations to control S. suis infection include focused and careful choice and appropriate use of antimicrobials, together with preventive measures intended to improve swine management.

Impact of Gram stain results on initial treatment selection in patients with ventilator-associated pneumonia: a retrospective analysis of two treatment algorithms.

PubMed

Yoshimura, Jumpei; Kinoshita, Takahiro; Yamakawa, Kazuma; Matsushima, Asako; Nakamoto, Naoki; Hamasaki, Toshimitsu; Fujimi, Satoshi

2017-06-19

Ventilator-associated pneumonia (VAP) is a common and serious problem in intensive care units (ICUs). Several studies have suggested that the Gram stain of endotracheal aspirates is a useful method for accurately diagnosing VAP. However, the usefulness of the Gram stain in predicting which microorganisms cause VAP has not been established. The purpose of this study was to evaluate whether a Gram stain of endotracheal aspirates could be used to determine appropriate initial antimicrobial therapy for VAP. Data on consecutive episodes of microbiologically confirmed VAP were collected from February 2013 to February 2016 in the ICU of a tertiary care hospital in Japan. We constructed two hypothetical empirical antimicrobial treatment algorithms for VAP: a guidelines-based algorithm (GLBA) based on the recommendations of the American Thoracic Society-Infectious Diseases Society of America (ATS-IDSA) guidelines and a Gram stain-based algorithm (GSBA) which limited the choice of initial antimicrobials according to the results of bedside Gram stains. The GLBA and the GSBA were retrospectively reviewed for each VAP episode. The initial coverage rates and the selection of broad-spectrum antimicrobial agents were compared between the two algorithms. During the study period, 219 suspected VAP episodes were observed and 131 episodes were assessed for analysis. Appropriate antimicrobial coverage rates were not significantly different between the two algorithms (GLBA 95.4% versus GSBA 92.4%; p = 0.134). The number of episodes for which antimethicillin-resistant Staphylococcus aureus agents were selected as an initial treatment was larger in the GLBA than in the GSBA (71.0% versus 31.3%; p < 0.001), as were the number of episodes for which antipseudomonal agents were recommended as an initial treatment (70.2% versus 51.9%; p < 0.001). Antimicrobial treatment based on Gram stain results may restrict the administration of broad-spectrum antimicrobial agents without increasing the risk of treatment failure. UMIN-CTR, UMIN000026457 . Registered 8 March 2017 (retrospectively registered).

Antimicrobial-Coated Granules for Disinfecting Water

NASA Technical Reports Server (NTRS)

Akse, James R.; Holtsnider, John T.; Kliestik, Helen

2011-01-01

Methods of preparing antimicrobialcoated granules for disinfecting flowing potable water have been developed. Like the methods reported in the immediately preceding article, these methods involve chemical preparation of substrate surfaces (in this case, the surfaces of granules) to enable attachment of antimicrobial molecules to the surfaces via covalent bonds. A variety of granular materials have been coated with a variety of antimicrobial agents that include antibiotics, bacteriocins, enzymes, bactericides, and fungicides. When employed in packed beds in flowing water, these antimicrobial-coated granules have been proven effective against gram-positive bacteria, gram-negative bacteria, fungi, and viruses. Composite beds, consisting of multiple layers containing different granular antimicrobial media, have proven particularly effective against a broad spectrum of microorganisms. These media have also proven effective in enhancing or potentiating the biocidal effects of in-line iodinated resins and of very low levels of dissolved elemental iodine.

Graphene Materials in Antimicrobial Nanomedicine: Current Status and Future Perspectives.

PubMed

Karahan, Hüseyin Enis; Wiraja, Christian; Xu, Chenjie; Wei, Jun; Wang, Yilei; Wang, Liang; Liu, Fei; Chen, Yuan

2018-03-05

Graphene materials (GMs), such as graphene, graphene oxide (GO), reduced GO (rGO), and graphene quantum dots (GQDs), are rapidly emerging as a new class of broad-spectrum antimicrobial agents. This report describes their state-of-the-art and potential future covering both fundamental aspects and biomedical applications. First, the current understanding of the antimicrobial mechanisms of GMs is illustrated, and the complex picture of underlying structure-property-activity relationships is sketched. Next, the different modes of utilization of antimicrobial GMs are explained, which include their use as colloidal dispersions, surface coatings, and photothermal/photodynamic therapy agents. Due to their practical relevance, the examples where GMs function as synergistic agents or release platforms for metal ions and/or antibiotic drugs are also discussed. Later, the applicability of GMs in the design of wound dressings, infection-protective coatings, and antibiotic-like formulations ("nanoantibiotics") is assessed. Notably, to support our assessments, the existing clinical applications of conventional carbon materials are also evaluated. Finally, the key hurdles of the field are highlighted, and several possible directions for future investigations are proposed. We hope that the roadmap provided here will encourage researchers to tackle remaining challenges toward clinical translation of promising research findings and help realize the potential of GMs in antimicrobial nanomedicine. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Antibacterial synergic effect of honey from two stingless bees: Scaptotrigona bipunctata Lepeletier, 1836, and S. postica Latreille, 1807

NASA Astrophysics Data System (ADS)

Nishio, E. K.; Ribeiro, J. M.; Oliveira, A. G.; Andrade, C. G. T. J.; Proni, E. A.; Kobayashi, R. K. T.; Nakazato, G.

2016-02-01

Several studies have tested antimicrobial activity of combinations of honey and various substances. In this study, we tested a combination of two stingless bee honeys against various bacterial strains. In particular: the antibacterial activity of honeys produced by Scaptotrigona bipunctata (SB) and Scaptotrigona postica (SP) was evaluated against Gram-positive and Gram-negative bacterial strains by agar well diffusion assays, minimum inhibitory concentration (MIC) assessment, construction of growth and viability curves and scanning electron microscopy (SEM). The interaction of the two honeys was also evaluated by the checkerboard assay. Inhibition zones ranged from 8 to 22 mm. The MIC values of the individual honeys ranged from 0.62 to 10% (v v-1) and decreased to 1/4 to 1/32 when the honeys were combined. SEM images showed division inhibition and cell wall disruption for the SB and SP honeys, respectively, and these alterations were observed in same field when the SB and SP honeys were combined. This study demonstrated that the natural honeys possess in vitro antimicrobial activity against Gram-positive and Gram-negative bacteria, including multidrug-resistant strains. Combination of the SB and SP honeys could lead to the development of new broad-spectrum antimicrobials that have the potential to prevent the emergence of resistant bacterial strains.

Antibacterial synergic effect of honey from two stingless bees: Scaptotrigona bipunctata Lepeletier, 1836, and S. postica Latreille, 1807

PubMed Central

Nishio, E. K.; Ribeiro, J. M.; Oliveira, A. G.; Andrade, C. G. T. J.; Proni, E. A.; Kobayashi, R. K. T.; Nakazato, G.

2016-01-01

Several studies have tested antimicrobial activity of combinations of honey and various substances. In this study, we tested a combination of two stingless bee honeys against various bacterial strains. In particular: the antibacterial activity of honeys produced by Scaptotrigona bipunctata (SB) and Scaptotrigona postica (SP) was evaluated against Gram-positive and Gram-negative bacterial strains by agar well diffusion assays, minimum inhibitory concentration (MIC) assessment, construction of growth and viability curves and scanning electron microscopy (SEM). The interaction of the two honeys was also evaluated by the checkerboard assay. Inhibition zones ranged from 8 to 22 mm. The MIC values of the individual honeys ranged from 0.62 to 10% (v v−1) and decreased to 1/4 to 1/32 when the honeys were combined. SEM images showed division inhibition and cell wall disruption for the SB and SP honeys, respectively, and these alterations were observed in same field when the SB and SP honeys were combined. This study demonstrated that the natural honeys possess in vitro antimicrobial activity against Gram-positive and Gram-negative bacteria, including multidrug-resistant strains. Combination of the SB and SP honeys could lead to the development of new broad-spectrum antimicrobials that have the potential to prevent the emergence of resistant bacterial strains. PMID:26869239

In vitro antimicrobial potential of extracts and phytoconstituents from Gymnema sylvestre R.Br. leaves and their biosafety evaluation.

PubMed

Arora, Daljit Singh; Sood, Henna

2017-12-01

The in vitro antimicrobial screening of Gymnema sylvestre leaves against 13 test pathogens established its broad spectrum activity with average inhibition zone ranging from 14 to 23 mm. The antimicrobial activity of the classically- optimized aqueous extract was enhanced up to 1.45 folds, when subjected to statistical optimization using Response Surface Methodology (RSM) and was thermostable. Ethyl acetate was found to be the best organic extractant with Klebsiella pneumoniae 1 (31.5 mm) and Staphylococcus epidermidis (25.5 mm) being the most sensitive among Gram negative and Gram positive bacteria, respectively. Among the major group of phytoconstituents detected, tannins were the most abundant followed by flavonoids and phytosterols, while triterpenes were absent. Flavonoids and cardiac glycosides exhibited a broad range of antimicrobial potential, with inhibition zone ranging from 13 to 35 mm, where Candida albicans was the most sensitive organism. Ethyl acetate extract showed better potency with lowest Minimum inhibitory concentration (0.1-1 mg ml -1 ) than the aqueous extract (1-3 mg ml -1 ) and all partially purified phytoconstituents (0.1-10 mg ml -1 ). The ethyl acetate extract and flavonoids were highly potent, as they exhibited a total activity potency ranging from 41.4 to 1045 ml g -1 . Time kill studies revealed their microbicidal action, where ethyl acetate extract had a kill time from 0 to 12 h. However, among phytoconstituents, flavonoids were the most effective (0-8 h). The MIC and time kill study was also compared to that of standard antibiotics. These findings indicate that Gymnema sylvestre can be a potential source for development of leading metabolites against pathogens of clinical importance like Pseudomonas aeruginosa, Candida albicans, Escherichia coli, Staphylococcus aureus etc. They were neither mutagenic nor cytotoxic, as revealed by Ames and MTT assay.

Novel synthetic analogues of avian β-defensin-12: the role of charge, hydrophobicity, and disulfide bridges in biological functions.

PubMed

Yang, Ming; Zhang, Chunye; Zhang, Michael Z; Zhang, Shuping

2017-02-23

Avian β-defensins (AvBD) possess broad-spectrum antimicrobial, LPS neutralizing and chemotactic properties. AvBD-12 is a chemoattractant for avian immune cells and mammalian dendritic cells (JAWSII) - a unique feature that is relevant to the applications of AvBDs as chemotherapeutic agents in mammalian hosts. To identify the structural components essential to various biological functions, we have designed and evaluated seven AvBD analogues. In the first group of analogues, the three conserved disulfide bridges were eliminated by replacing cysteines with alanine and serine residues, peptide hydrophobicity and charge were increased by changing negatively charged amino acid residues to hydrophobic (AvBD-12A1) or positively charged residues (AvBD-12A2 and AvBD-12A3). All three analogues in this group showed improved antimicrobial activity, though AvBD-12A3, with a net positive charge of +9, hydrophobicity of 40% and a predicted CCR2 binding domain, was the most potent antimicrobial peptide. AvBD-12A3 also retained more than 50% of wild type chemotactic activity. In the second group of analogues (AvBD-12A4 to AvBD-12A6), one to three disulfide bridges were removed via substitution of cysteines with isosteric amino acids. Their antimicrobial activity was compromised and chemotactic activity abolished. The third type of analogue was a hybrid that had the backbone of AvBD-12 and positively charged amino acid residues AvBD-6. The antimicrobial and chemotactic activities of the hybrid resembled that of AvBD-6 and AvBD-12, respectively. While the net positive charge and charge distribution have a dominating effect on the antimicrobial potency of AvBDs, the three conserved disulfide bridges are essential to the chemotactic property and the maximum antimicrobial activity. Analogue AvBD-12A3 with a high net positive charge, a moderate degree of hydrophobicity and a CCR2-binding domain can serve as a template for the design of novel antimicrobial peptides with chemotactic property and salt resistance.

Antimicrobial potential of Dialium guineense (Wild.) stem bark on some clinical isolates in Nigeria.

PubMed

Olajubu, Fa; Akpan, I; Ojo, DA; Oluwalana, Sa

2012-01-01

The persistent increase in the number of antibiotic-resistant strains of microorganisms has led to the development of more potent but also more expensive antibiotics. In most developing countries of the world these antibiotics are not readily affordable, thus making compliance difficult. This calls for research into alternative sources of antimicrobials. Dialium guineense is a shrub of the family Leguminosae. Its stem bark is used for the treatment of cough, toothache, and bronchitis. Despite the acclaimed efficacy of D guineense, there is no scientific evidence in its support. This work was carried out to assess the antimicrobial activity of D guineense in vitro against some clinical isolates. D guineense stem bark was collected and 50 gm of air-dried and powdered stem bark of the plant was soaked for 72 hours in 1 l of each of the six solvents used in this study. Each mixture was refluxed, agitated at 200 rpm for 1 hour, filtered using Whatman No. 1 filter paper and, finally, freeze dried. The extracts were then tested for antimicrobial activity using the agar diffusion method. The highest percentage yield of 23.2% was obtained with ethanol. Phytochemical screening showed that D guineense contains anthraquinone, alkaloids, flavonoids, tannins, and saponins. The antimicrobial activity of the extracts revealed a broad spectrum of activity, with Salmonella typhi and Staphylococcus aureusa showing the greatest zones of inhibition (18.0 mm). Only Candida albicans among the fungi tested was inhibited by the extract. The greatest zone of inhibition among the fractions was 16.0 mm. D guineense exhibited bactericidal activity at the 7th and 9th hours against Streptococcus pneumoniae and S. aureus 25923 while the 10th hour against S. typhi and C. albicans. The greatest activity was noted against S pneumoniae, where there was reduced viable cell count after 6 hours of exposure. Stem bark extract of D guineense (Wild.) has the potential to be developed into an antimicrobial agent.

The Development of Antimicrobial α-AApeptides that Suppress Pro-inflammatory Immune Responses

PubMed Central

Padhee, Shruti; Smith, Christina; Wu, Haifan; Li, Yaqiong; Manoj, Namitha; Qiao, Qiao; Khan, Zoya; Cao, Chuanhai

2014-01-01

Herein we describe the development of a new class of antimicrobial and anti-infective peptidomimetics – cyclic lipo-α-AApeptides. They have potent and broad-spectrum antibacterial activity against a range of clinically relevant pathogens, including both multidrug-resistant Gram-positive and Gram-negative bacteria. Fluorescence microscopy suggests that cyclic lipo-α-AApeptides kill bacteria by disrupting bacterial membranes, possibly through a mechanism similar to that of cationic host defense peptides (HDPs). Furthermore, the cyclic lipo-α-AApeptide can mimic cationic host-defense peptides by antagonizing Toll-Like Receptor 4 (TLR4) signaling responses and suppressing pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α). Our results suggest that by mimicking host-defense peptides (HDPs), cyclic lipo-α-AApeptides may emerge to be a new class of antibiotic agents through direct bacteria killing, as well as novel anti-infective agents through immunomodulation. PMID:24677440

Use of rifaximin in gastrointestinal and liver diseases.

PubMed

Shayto, Rani H; Abou Mrad, Rachel; Sharara, Ala I

2016-08-07

Rifaximin is a broad spectrum oral antibiotic with antimicrobial activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria. It is poorly absorbed and thus has a highly favorable safety profile. Rifaximin has been shown to be effective in the treatment of traveler's diarrhea, functional bloating and irritable bowel syndrome, small bowel bacterial overgrowth and in the prevention of recurrent overt hepatic encephalopathy. In addition, there is emerging evidence for a possible beneficial effect of rifaximin in the treatment of uncomplicated diverticular disease and in the prevention of recurrent diverticulitis. The use of rifaximin is associated with a low incidence of development, or persistence of spontaneous bacterial mutants. Moreover, the development of important drug resistance among extra-intestinal flora during rifaximin therapy is unlikely because of minimal systemic absorption and limited cross-resistance of rifaximin with other antimicrobials. This review addresses the current and emerging role of rifaximin in the treatment of gastrointestinal and liver disorders.

Antimicrobial Peptide Production and Purification.

PubMed

Suda, Srinivas; Field, Des; Barron, Niall

2017-01-01

Antimicrobial peptides (AMPs) are natural defense compounds which are synthesized as ribosomal gene-encoded pre-peptides and produced by all living organisms. AMPs are small peptides, usually cationic and typically have hydrophobic residues which interact with cell membranes and have either a narrow or broad spectrum of biological activity. AMPs are isolated from the natural host or heterologously expressed in other hosts such as Escherichia coli. The proto-typical lantibiotic Nisin is a widely used AMP that is produced by the food-grade organism Lactococcus lactis. Although AMP production and purification procedures require optimization for individual AMPs, the Nisin production and purification protocol outlined in this chapter can be easily applied with minor modifications for the production and purification of other lantibiotics or AMPs. While Nisin is produced and secreted into the supernatant, steps to recover Nisin from both cell-free supernatant and cell pellet are outlined in detail.

Antagonistic intestinal microflora produces antimicrobial substance inhibitory to Pseudomonas species and other spoilage organisms.

PubMed

Hatew, Bayissa; Delessa, Tenagne; Zakin, Vered; Gollop, Natan

2011-10-01

Chicken intestine harbors a vast number of bacterial strains. In the present study, antimicrobial substance produced by lactic acid bacteria (LAB) isolated from the gastrointestinal tract of healthy chicken was detected, characterized, and purified. Based on 16S rRNA sequencing, the bacteria were identified as Lactobacillus plantarum vN. The antimicrobial substance produced by this bacterium was designated vN-1 and exhibited a broad-spectrum of activity against many important pathogenic and spoilage microorganisms, including Pseudomonas aeruginosa, Staphylococcus aureus, Micrococcus luteus, Salmonella Typhimurium, and Erwinia amylovova. vN-1 was determined to be thermostable, insensitive to pH values ranging from 2.0 to 8.0, resistant to various organic solvents and to enzymatic inactivation. The inhibition kinetics displayed a bactericidal mode of action. This study revealed an antimicrobial substance with low molecular mass of less than 1 kDa as determined by ultrafiltration and having features not previously reported for LAB isolated from chicken intestines. The detection of this antimicrobial substance addresses an important aspect of biotechnological control agents of spoilage caused by Pseudomonas spp. and promises the possibility for preservation of refrigerated poultry meat. Practical Application:  The newly characterized antimicrobial substance and designated as vN-1 may have the potential to be used in food preservation. © 2011 Institute of Food Technologists®

Evaluation of early antimicrobial therapy adaptation guided by the BetaLACTA® test: a case-control study.

PubMed

Garnier, Marc; Rozencwajg, Sacha; Pham, Tài; Vimont, Sophie; Blayau, Clarisse; Hafiani, Mehdi; Fulgencio, Jean-Pierre; Bonnet, Francis; Mainardi, Jean-Luc; Arlet, Guillaume; Fartoukh, Muriel; Gallah, Salah; Quesnel, Christophe

2017-06-28

Rapid diagnostic tests detecting microbial resistance are needed for limiting the duration of inappropriateness of empirical antimicrobial therapy (EAT) in intensive care unit patients, besides reducing the use of broad-spectrum antibiotics. We hypothesized that the betaLACTA® test (BLT) could lead to early increase in the adequacy of antimicrobial therapy. This was a case-control study. Sixty-one patients with BLT-guided adaptation of EAT were prospectively included, and then matched with 61 "controls" having similar infection characteristics (community or hospital-acquired, and source of infection), in whom EAT was conventionally adapted to antibiogram results. Endpoints were to compare the proportion of appropriate (primary endpoint) and optimal (secondary endpoint) antimicrobial therapies with each of the two strategies, once microbiological sample culture results were available. Characteristics of patients, infections and EAT at inclusion were similar between groups. Nine early escalations of EAT occurred in the BLT-guided adaptation group, reaching 98% appropriateness vs. 77% in the conventional adaptation group (p < 0.01). The BLT reduced the time until escalation of an inappropriate EAT from 50.5 (48-73) to 27 (24-28) hours (p < 0.01). Seventeen early de-escalations occurred in the BLT-guided adaptation group, compared to one in the conventional adaptation group, reducing patients' exposure to broad-spectrum beta-lactam such as carbapenems. In multivariate analysis, use of the BLT was strongly associated with early appropriate (OR = 18 (3.4-333.8), p = 0.006) and optimal (OR = 35.5 (9.6-231.9), p < 0.001) antimicrobial therapies. Safety parameters were similar between groups. Our study suggests that a BLT-guided adaptation strategy may allow early beta-lactam adaptation from the first 24 hours following the beginning of sepsis management.

Antimicrobial, Anthelmintic, and Antiviral Activity of Plants Traditionally Used for Treating Infectious Disease in the Similipal Biosphere Reserve, Odisha, India

PubMed Central

Panda, Sujogya K.; Padhi, Laxmipriya; Leyssen, Pieter; Liu, Maoxuan; Neyts, Johan; Luyten, Walter

2017-01-01

In the present study, we tested in vitro different parts of 35 plants used by tribals of the Similipal Biosphere Reserve (SBR, Mayurbhanj district, India) for the management of infections. From each plant, three extracts were prepared with different solvents (water, ethanol, and acetone) and tested for antimicrobial (E. coli, S. aureus, C. albicans); anthelmintic (C. elegans); and antiviral (enterovirus 71) bioactivity. In total, 35 plant species belonging to 21 families were recorded from tribes of the SBR and periphery. Of the 35 plants, eight plants (23%) showed broad-spectrum in vitro antimicrobial activity (inhibiting all three test strains), while 12 (34%) exhibited narrow spectrum activity against individual pathogens (seven as anti-staphylococcal and five as anti-candidal). Plants such as Alangium salviifolium, Antidesma bunius, Bauhinia racemosa, Careya arborea, Caseria graveolens, Cleistanthus patulus, Colebrookea oppositifolia, Crotalaria pallida, Croton roxburghii, Holarrhena pubescens, Hypericum gaitii, Macaranga peltata, Protium serratum, Rubus ellipticus, and Suregada multiflora showed strong antibacterial effects, whilst Alstonia scholaris, Butea monosperma, C. arborea, C. pallida, Diospyros malbarica, Gmelina arborea, H. pubescens, M. peltata, P. serratum, Pterospermum acerifolium, R. ellipticus, and S. multiflora demonstrated strong antifungal activity. Plants such as A. salviifolium, A. bunius, Aporosa octandra, Barringtonia acutangula, C. graveolens, C. pallida, C. patulus, G. arborea, H. pubescens, H. gaitii, Lannea coromandelica, M. peltata, Melastoma malabathricum, Millettia extensa, Nyctanthes arbor-tristis, P. serratum, P. acerifolium, R. ellipticus, S. multiflora, Symplocos cochinchinensis, Ventilago maderaspatana, and Wrightia arborea inhibit survival of C. elegans and could be a potential source for anthelmintic activity. Additionally, plants such as A. bunius, C. graveolens, C. patulus, C. oppositifolia, H. gaitii, M. extensa, P. serratum, R. ellipticus, and V. maderaspatana showed anti-enteroviral activity. Most of the plants, whose traditional use as anti-infective agents by the tribals was well supported, show in vitro inhibitory activity against an enterovirus, bacteria (E. coil, S. aureus), a fungus (C. albicans), or a nematode (C. elegans). PMID:29109684

Antimicrobial, Anthelmintic, and Antiviral Activity of Plants Traditionally Used for Treating Infectious Disease in the Similipal Biosphere Reserve, Odisha, India.

PubMed

Panda, Sujogya K; Padhi, Laxmipriya; Leyssen, Pieter; Liu, Maoxuan; Neyts, Johan; Luyten, Walter

2017-01-01

In the present study, we tested in vitro different parts of 35 plants used by tribals of the Similipal Biosphere Reserve (SBR, Mayurbhanj district, India) for the management of infections. From each plant, three extracts were prepared with different solvents (water, ethanol, and acetone) and tested for antimicrobial ( E. coli, S. aureus, C. albicans ); anthelmintic ( C. elegans ); and antiviral ( enterovirus 71 ) bioactivity. In total, 35 plant species belonging to 21 families were recorded from tribes of the SBR and periphery. Of the 35 plants, eight plants (23%) showed broad-spectrum in vitro antimicrobial activity (inhibiting all three test strains), while 12 (34%) exhibited narrow spectrum activity against individual pathogens (seven as anti-staphylococcal and five as anti-candidal). Plants such as Alangium salviifolium, Antidesma bunius, Bauhinia racemosa, Careya arborea, Caseria graveolens, Cleistanthus patulus, Colebrookea oppositifolia, Crotalaria pallida, Croton roxburghii, Holarrhena pubescens, Hypericum gaitii, Macaranga peltata, Protium serratum, Rubus ellipticus , and Suregada multiflora showed strong antibacterial effects, whilst Alstonia scholaris, Butea monosperma, C. arborea, C. pallida, Diospyros malbarica, Gmelina arborea, H. pubescens, M. peltata, P. serratum, Pterospermum acerifolium, R. ellipticus , and S. multiflora demonstrated strong antifungal activity. Plants such as A. salviifolium, A. bunius, Aporosa octandra, Barringtonia acutangula, C. graveolens, C. pallida, C. patulus, G. arborea, H. pubescens, H. gaitii, Lannea coromandelica, M. peltata, Melastoma malabathricum, Millettia extensa, Nyctanthes arbor-tristis, P. serratum, P. acerifolium, R. ellipticus, S. multiflora, Symplocos cochinchinensis, Ventilago maderaspatana , and Wrightia arborea inhibit survival of C. elegans and could be a potential source for anthelmintic activity. Additionally, plants such as A. bunius, C. graveolens, C. patulus, C. oppositifolia, H. gaitii, M. extensa, P. serratum, R. ellipticus , and V. maderaspatana showed anti-enteroviral activity. Most of the plants, whose traditional use as anti-infective agents by the tribals was well supported, show in vitro inhibitory activity against an enterovirus, bacteria ( E. coil, S. aureus ), a fungus ( C. albicans ), or a nematode ( C. elegans ).

Bactericidal activities of GM flax seedcake extract on pathogenic bacteria clinical strains.

PubMed

Zuk, Magdalena; Dorotkiewicz-Jach, Agata; Drulis-Kawa, Zuzanna; Arendt, Malgorzata; Kulma, Anna; Szopa, Jan

2014-07-29

The antibiotic resistance of pathogenic microorganisms is a worldwide problem. Each year several million people across the world acquire infections with bacteria that are antibiotic-resistant, which is costly in terms of human health. New antibiotics are extremely needed to overcome the current resistance problem. Transgenic flax plants overproducing compounds from phenylpropanoid pathway accumulate phenolic derivatives of potential antioxidative, and thus, antimicrobial activity. Alkali hydrolyzed seedcake extract containing coumaric acid, ferulic acid, caffeic acid, and lignan in high quantities was used as an assayed against pathogenic bacteria (commonly used model organisms and clinical strains). It was shown that the extract components had antibacterial activity, which might be useful as a prophylactic against bacterial infection. Bacteria topoisomerase II (gyrase) inhibition and genomic DNA disintegration are suggested to be the main reason for rendering antibacterial action. The data obtained strongly suggest that the seedcake extract preparation is a suitable candidate for antimicrobial action with a broad spectrum and partial selectivity. Such preparation can be applied in cases where there is a risk of multibacterial infection and excellent answer on global increase in multidrug resistance in pathogenic bacteria.

Anethole induces apoptotic cell death accompanied by reactive oxygen species production and DNA fragmentation in Aspergillus fumigatus and Saccharomyces cerevisiae.

PubMed

Fujita, Ken-Ichi; Tatsumi, Miki; Ogita, Akira; Kubo, Isao; Tanaka, Toshio

2014-02-01

trans-Anethole (anethole), a major component of anise oil, has a broad antimicrobial spectrum, and antimicrobial activity that is weaker than that of other antibiotics on the market. When combined with polygodial, nagilactone E, and n-dodecanol, anethole has been shown to possess significant synergistic antifungal activity against a budding yeast, Saccharomyces cerevisiae, and a human opportunistic pathogenic yeast, Candida albicans. However, the antifungal mechanism of anethole has not been completely determined. We found that anethole stimulated cell death of a human opportunistic pathogenic fungus, Aspergillus fumigatus, in addition to S. cerevisiae. The anethole-induced cell death was accompanied by reactive oxygen species production, metacaspase activation, and DNA fragmentation. Several mutants of S. cerevisiae, in which genes related to the apoptosis-initiating execution signals from mitochondria were deleted, were resistant to anethole. These results suggest that anethole-induced cell death could be explained by oxidative stress-dependent apoptosis via typical mitochondrial death cascades in fungi, including A. fumigatus and S. cerevisiae. © 2014 FEBS.

Bark extract mediated green synthesis of silver nanoparticles: Evaluation of antimicrobial activity and antiproliferative response against osteosarcoma.

PubMed

Nayak, Debasis; Ashe, Sarbani; Rauta, Pradipta Ranjan; Kumari, Manisha; Nayak, Bismita

2016-01-01

In the current investigation we report the biosynthesis potentials of bark extracts of Ficus benghalensis and Azadirachta indica for production of silver nanoparticle without use of any external reducing or capping agent. The appearance of dark brown color indicated the complete nanoparticle synthesis which was further validated by absorbance peak by UV-vis spectroscopy. The morphology of the synthesized particles was characterized by Field emission- scanning electron microscopy (Fe-SEM) and atomic force microscopy (AFM). The X-ray diffraction (XRD) patterns clearly illustrated the crystalline phase of the synthesized nanoparticles. ATR-Fourier Transform Infrared (ATR-FTIR) spectroscopy was performed to identify the role of various functional groups in the nanoparticle synthesis. The synthesized nanoparticles showed promising antimicrobial activity against Gram negative (Escherichia coli, Pseudomonas aeruginosa and Vibrio cholerae) and Gram positive (Bacillus subtilis) bacteria. The synthesized nano Ag also showed antiproliferative activity against MG-63 osteosarcoma cell line in a dose dependent manner. Thus, these synthesized Ag nanoparticles can be used as a broad spectrum therapeutic agent against osteosarcoma and microorganisms. Copyright © 2015 Elsevier B.V. All rights reserved.

Structure-activity relationships of insect defensins

NASA Astrophysics Data System (ADS)

Koehbach, Johannes

2017-07-01

Insects make up the largest and most diverse group of organisms on earth with several million species to exist in total. Considering the sheer number of insect species and the vast variety of ways they interact with their environment through chemistry, it is clear that they have significant potential as a source of new lead molecules. They have adapted to a range of ecological habitats and exhibit a symbiotic lifestyle with various microbes such as bacteria and fungi. Accordingly, numerous antimicrobial compounds have been identified including for example defensin peptides. Insect defensins were found to have broad-spectrum activity against various gram-positive/negative bacteria as well as fungi. They exhibit a unique structural topology involving the complex arrangement of three disulfide bonds as well as an alpha helix and beta sheets, which is known as cysteine-stabilized αβ motif. Their stability and amenability to peptide engineering make them promising candidates for the development of novel antibiotics lead molecules. This review highlights the current knowledge regarding the structure-activity relationships of insect defensin peptides and provides basis for future studies focusing on the rational design of novel cysteine-rich antimicrobial peptides.

Targeted simplification versus antipseudomonal broad-spectrum beta-lactams in patients with bloodstream infections due to Enterobacteriaceae (SIMPLIFY): a study protocol for a multicentre, open-label, phase III randomised, controlled, non-inferiority clinical trial.

PubMed

López-Cortés, Luis Eduardo; Rosso-Fernández, Clara; Núñez-Núñez, María; Lavín-Alconero, Lucía; Bravo-Ferrer, José; Barriga, Ángel; Delgado, Mercedes; Lupión, Carmen; Retamar, Pilar; Rodríguez-Baño, Jesús

2017-06-09

Within the context of antimicrobial stewardship programmes, de-escalation of antimicrobial therapy is one of the proposed strategies for reducing the unnecessary use of broad-spectrum antibiotics (BSA). The empirical treatment of nosocomial and some healthcare-associated bloodstream infections (BSI) frequently includes a beta-lactam with antipseudomonal activity as monotherapy or in combination with other drugs, so there is a great opportunity to optimise the empirical therapy based on microbiological data. De-escalation is assumed as standard of care for experts in infectious diseases. However, it is less frequent than it would desirable. The SIMPLIFY trial is a multicentre, open-label, non-inferiority phase III randomised controlled clinical trial, designed as a pragmatic 'real-practice' trial. The aim of this trial is to demonstrate the non-inferiority of de-escalation from an empirical beta-lactam with antipseudomonal activity to a targeted narrow-spectrum antimicrobial in patients with BSI due to Enterobacteriaceae . The primary outcome is clinical cure, which will be assessed at the test of cure visit. It will be conducted at 19 Spanish public and university hospitals. Each participating centre has obtained the approval of the ethics review committee, the agreement of the directors of the institutions and authorisation from the Spanish Regulatory Agency (Agencia Española del Medicamento y Productos Sanitarios). Data will be presented at international conferences and published in peer-reviewed journals. Strategies to reduce the use of BSA should be a priority. Most of the studies that support de-escalation are observational, retrospective and heterogeneous. A recent Cochrane review stated that well-designed clinical trials should be conducted to assess the safety and efficacy of de-escalation. The European Union Clinical Trials Register: EudraCT number 2015-004219-19. Clinical trials.gov: NCT02795949. Protocol version: V.2.0, dated 16 May 2016. All items from the WHO Trial Registration Data Set are included in the registry. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Spatial Variability of Factors Influencing the Distribution of Triclosan in Sediments and Water of an Urbanized Estuarine Embayment

EPA Science Inventory

Triclosan (TCS) is a broad spectrum anti-microbial compound added to many consumer and personal care products. TCS enters water bodies primarily through wastewater treatment plant (WWTP) effluent and may be introduced by combined sewer overflows or surface water runoff. In estu...

The effect of triclosan on the uterotrophic response to extended doses of ethinyl estradiol in the weanling rat

EPA Science Inventory

Triclosan (TCS), a broad-spectrum antimicrobial agent found in many personal care products, has been detected in humans and has been shown to interact with endocrine systems in rats. We previously reported that TCS potentiated the estrogenic effect of ethinyl estradiol (EE) on u...

An E3 Ubiquitin Ligase-BAG Protein Module Controls Plant Innate Immunity and Broad-Spectrum Disease Resistance.

PubMed

You, Quanyuan; Zhai, Keran; Yang, Donglei; Yang, Weibing; Wu, Jingni; Liu, Junzhong; Pan, Wenbo; Wang, Jianjun; Zhu, Xudong; Jian, Yikun; Liu, Jiyun; Zhang, Yingying; Deng, Yiwen; Li, Qun; Lou, Yonggen; Xie, Qi; He, Zuhua

2016-12-14

Programmed cell death (PCD) and immunity in plants are tightly controlled to promote antimicrobial defense while preventing autoimmunity. However, the mechanisms contributing to this immune homeostasis are poorly understood. Here, we isolated a rice mutant ebr1 (enhanced blight and blast resistance 1) that shows enhanced broad-spectrum bacterial and fungal disease resistance, but displays spontaneous PCD, autoimmunity, and stunted growth. EBR1 encodes an E3 ubiquitin ligase that interacts with OsBAG4, which belongs to the BAG (Bcl-2-associated athanogene) family that functions in cell death, growth arrest, and immune responses in mammals. EBR1 directly targets OsBAG4 for ubiquitination-mediated degradation. Elevated levels of OsBAG4 in rice are necessary and sufficient to trigger PCD and enhanced disease resistance to pathogenic infection, most likely by activating pathogen-associated molecular patterns-triggered immunity (PTI). Together, our study suggests that an E3-BAG module orchestrates innate immune homeostasis and coordinates the trade-off between defense and growth in plants. Copyright © 2016 Elsevier Inc. All rights reserved.

Staphylococcal antimicrobial peptides: relevant properties and potential biotechnological applications.

PubMed

Bastos, M C F; Ceotto, H; Coelho, M L V; Nascimento, J S

2009-01-01

Bacteriocins are bacterial antimicrobial peptides with bactericidal activity against other bacteria. Staphylococcins are bacteriocins produced by staphylococci, which are Gram-positive bacteria with medical and veterinary importance. Most bacteriocins produced by staphylococci are either lantibiotics (e.g., Pep5, epidermin, epilancin K7, epicidin 280, staphylococcin C55/BacR1, and nukacin ISK-1) or class II bacteriocins (e.g., aureocins A70 and 53). Only one staphylococcin belonging to class III, lysostaphin, has been described so far. Production of staphylococcins is a self-protection mechanism that helps staphylococci to survive in their natural habitats. However, since these substances generally have a broad spectrum of activity, inhibiting several human and animal pathogens, they have potential biotechnological applications either as food preservatives or therapeutic agents. Due to the increasing consumer awareness of the risks derived not only from food-borne pathogens, but also from the artificial chemical preservatives used to control them, the interest in the discovery of natural food preservatives has increased considerably. The emergence and dissemination of antibiotic resistance among human and animal pathogens and their association with the use of antibiotics constitute a serious problem worldwide requiring effective measures for controlling their spread. Staphylococcins may be used, solely or in combination with other chemical agents, to avoid food contamination or spoilage and to prevent or treat bacterial infectious diseases. The use of combinations of antimicrobials is common in the clinical setting and expands the spectrum of organisms that can be targeted, prevents the emergence of resistant organisms, decreases toxicity by allowing lower doses of both agents and can result in synergistic inhibition.

Bio-inspired crosslinking and matrix-drug interactions for advanced wound dressings with long-term antimicrobial activity.

PubMed

Dhand, Chetna; Venkatesh, Mayandi; Barathi, Veluchami Amutha; Harini, Sriram; Bairagi, Samiran; Goh Tze Leng, Eunice; Muruganandham, Nandhakumar; Low, Kenny Zhi Wei; Fazil, Mobashar Hussain Urf Turabe; Loh, Xian Jun; Srinivasan, Dinesh Kumar; Liu, Shou Ping; Beuerman, Roger W; Verma, Navin Kumar; Ramakrishna, Seeram; Lakshminarayanan, Rajamani

2017-09-01

There is a growing demand for durable advanced wound dressings for the management of persistent infections after deep burn injuries. Herein, we demonstrated the preparation of durable antimicrobial nanofiber mats, by taking advantage of strong interfacial interactions between polyhydroxy antibiotics (with varying number of OH groups) and gelatin and their in-situ crosslinking with polydopamine (pDA) using ammonium carbonate diffusion method. Polydopamine crosslinking did not interfere with the antimicrobial efficacy of the loaded antibiotics. Interestingly, incorporation of antibiotics containing more number of alcoholic OH groups (N OH  ≥ 5) delayed the release kinetics with complete retention of antimicrobial activity for an extended period of time (20 days). The antimicrobials-loaded mats displayed superior mechanical and thermal properties than gelatin or pDA-crosslinked gelatin mats. Mats containing polyhydroxy antifungals showed enhanced aqueous stability and retained nanofibrous morphology under aqueous environment for more than 4 weeks. This approach can be expanded to produce mats with broad spectrum antimicrobial properties by incorporating the combination of antibacterial and antifungal drugs. Direct electrospinning of vancomycin-loaded electrospun nanofibers onto a bandage gauze and subsequent crosslinking produced non-adherent durable advanced wound dressings that could be easily applied to the injured sites and readily detached after treatment. In a partial thickness burn injury model in piglets, the drug-loaded mats displayed comparable wound closure to commercially available silver-based dressings. This prototype wound dressing designed for easy handling and with long-lasting antimicrobial properties represents an effective option for treating life-threatening microbial infections due to thermal injuries. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Biological and immunotoxicity evaluation of antimicrobial peptide-loaded coatings using a layer-by-layer process on titanium

PubMed Central

Shi, Jue; Liu, Yu; Wang, Ying; Zhang, Jing; Zhao, Shifang; Yang, Guoli

2015-01-01

The prevention and control of peri-implantitis is a challenge in dental implant surgery. Dental implants with sustained antimicrobial coating are an ideal way of preventing peri-implantitis. This study reports development of a non- immunotoxicity multilayered coating on a titanium surface that had sustained antimicrobial activity and limited early biofilm formation. In this study, the broad spectrum AMP, Tet213, was linked to collagen IV through sulfo-SMPB and has been renamed as AMPCol. The multilayer AMPCol coatings were assembled on smooth titanium surfaces using a LBL technique. Using XPS, AFM, contact angle analysis, and QCM, layer-by-layer accumulation of coating thickness was measured and increased surface wetting compared to controls was confirmed. Non-cytotoxicity to HaCaT and low erythrocyte hemolysis by the AMPCol coatings was observed. In vivo immunotoxicity assays showed IP administration of AMPCol did not effect serum immunoglobulin levels. This coating with controlled release of AMP decreased the growth of both a Gram-positive aerobe (Staphylococcus aureus) and a Gram-negative anaerobe (Porphyromonas gingivalis) up to one month. Early S. aureus biofilm formation was inhibited by the coating. The excellent long-term sustained antimicrobial activity of this multilayer coating is a potential method for preventing peri-implantitis through coated on the neck of implants before surgery. PMID:26548760

Avian Antimicrobial Host Defense Peptides: From Biology to Therapeutic Applications

PubMed Central

Zhang, Guolong; Sunkara, Lakshmi T.

2014-01-01

Host defense peptides (HDPs) are an important first line of defense with antimicrobial and immunomoduatory properties. Because they act on the microbial membranes or host immune cells, HDPs pose a low risk of triggering microbial resistance and therefore, are being actively investigated as a novel class of antimicrobials and vaccine adjuvants. Cathelicidins and β-defensins are two major families of HDPs in avian species. More than a dozen HDPs exist in birds, with the genes in each HDP family clustered in a single chromosomal segment, apparently as a result of gene duplication and diversification. In contrast to their mammalian counterparts that adopt various spatial conformations, mature avian cathelicidins are mostly α-helical. Avian β-defensins, on the other hand, adopt triple-stranded β-sheet structures similar to their mammalian relatives. Besides classical β-defensins, a group of avian-specific β-defensin-related peptides, namely ovodefensins, exist with a different six-cysteine motif. Like their mammalian counterparts, avian cathelicidins and defensins are derived from either myeloid or epithelial origin expressed in a majority of tissues with broad-spectrum antibacterial and immune regulatory activities. Structure-function relationship studies with several avian HDPs have led to identification of the peptide analogs with potential for use as antimicrobials and vaccine adjuvants. Dietary modulation of endogenous HDP synthesis has also emerged as a promising alternative approach to disease control and prevention in chickens. PMID:24583933

Comparison of antimicrobial peptide purification via free-flow electrophoresis and gel filtration chromatography.

PubMed

Xia, Zhi-Jun; Liu, Zhen; Kong, Fan-Zhi; Fan, Liu-Yin; Xiao, Hua; Cao, Cheng-Xi

2017-12-01

Antimicrobial peptides (AMPs) are usually small and cationic biomolecules with broad-spectrum antimicrobial activities against pathogens. Purifying them from complex samples is essential to study their physiochemical properties. In this work, free-flow zone electrophoresis (FFZE) was utilized to purify AMPs from yeast fermentation broth. Meanwhile, gel filtration chromatography (GFC) was conducted for comparison. The separation efficiency was evaluated by SDS-PAGE analysis of the fractions from both methods. Our results demonstrated as follows: (i) FFZE had more than 30-fold higher processing capacity as compared with GFC; (ii) FFZE could achieve 87% purity and 89% recovery rate while in GFC these parameters were about 93 and 82%, respectively; (iii) the former had ∼2-fold dilution but the latter had ∼13-fold dilution. Furthermore, Tricine-SDS-PAGE, Native-PAGE, and gel IEF were carried out to characterize the purified AMPs. We found that two peptides existed as a pair with the molecular mass of ∼5.5 and 7.0 kDa, while the same pI 7.8. These two peptides were proved to have the antimicrobial activity through the standardized agar diffusion method. Therefore, FFZE could be used to continuously purify AMPs with high bioactivity, which will lead to its wide application in the clinical and pharmaceutical fields. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Antimicrobial Properties of Plant Essential Oils against Human Pathogens and Their Mode of Action: An Updated Review

PubMed Central

2016-01-01

A wide range of medicinal and aromatic plants (MAPs) have been explored for their essential oils in the past few decades. Essential oils are complex volatile compounds, synthesized naturally in different plant parts during the process of secondary metabolism. Essential oils have great potential in the field of biomedicine as they effectively destroy several bacterial, fungal, and viral pathogens. The presence of different types of aldehydes, phenolics, terpenes, and other antimicrobial compounds means that the essential oils are effective against a diverse range of pathogens. The reactivity of essential oil depends upon the nature, composition, and orientation of its functional groups. The aim of this article is to review the antimicrobial potential of essential oils secreted from MAPs and their possible mechanisms of action against human pathogens. This comprehensive review will benefit researchers who wish to explore the potential of essential oils in the development of novel broad-spectrum key molecules against a broad range of drug-resistant pathogenic microbes. PMID:28090211

Targeting virulence: salmochelin modification tunes the antibacterial activity spectrum of β-lactams for pathogen-selective killing of Escherichia coli † †Electronic supplementary information (ESI) available: Tables of bacterial strains employed in this study, iron content of the antimicrobial activity medium, characterization of GlcEnt–Amp/Amx 7–10, GlcEnt-PEG3-N3 12–13, and BLAST search for iroN sequence. Figures of HPLC traces of MceC- and IroB-catalyzed glucosylation of Ent-PEG3-N3 11, optical absorption spectra of GlcEnt–Amp/Amx 7–10, additional antimicrobial activity assays, time-kill kinetics, competition assays for FepA and IroN recognition, mixed-species antimicrobial activity assays, Lcn2 effect on antibacterial activity of GlcEnt–Amp/Amx 7–10, and cytotoxicity assays against T84 cells. See DOI: 10.1039/c5sc00962f Click here for additional data file.

PubMed Central

Chairatana, Phoom; Zheng, Tengfei

2015-01-01

New antibiotics are required to treat bacterial infections and counteract the emergence of antibiotic resistance. Pathogen-specific antibiotics have several advantages over broad-spectrum drugs, which include minimal perturbation to the commensal microbiota. We present a strategy for targeting antibiotics to bacterial pathogens that utilises the salmochelin-mediated iron uptake machinery of Gram-negative Escherichia coli. Salmochelins are C-glucosylated derivatives of the siderophore enterobactin. The biosynthesis and utilisation of salmochelins are important for virulence because these siderophores allow pathogens to acquire iron and evade the enterobactin-scavenging host-defense protein lipocalin-2. Inspired by the salmochelins, we report the design and chemoenzymatic preparation of glucosylated enterobactin–β-lactam conjugates that harbour the antibiotics ampicillin (Amp) and amoxicillin (Amx), hereafter GlcEnt–Amp/Amx. The GlcEnt scaffolds are based on mono- and diglucosylated Ent where one catechol moiety is functionalized at the C5 position for antibiotic attachment. We demonstrate that GlcEnt–Amp/Amx provide up to 1000-fold enhanced antimicrobial activity against uropathogenic E. coli relative to the parent β-lactams. Moreover, GlcEnt–Amp/Amx based on a diglucosylated Ent (DGE) platform selectively kill uropathogenic E. coli that express the salmochelin receptor IroN in the presence of non-pathogenic E. coli and other bacterial strains that include the commensal microbe Lactobacillus rhamnosus GG. Moreover, GlcEnt–Amp/Amx evade the host-defense protein lipocalin-2, and exhibit low toxicity to mammalian cells. Our work establishes that siderophore–antibiotic conjugates provide a strategy for targeting virulence, narrowing the activity spectrum of antibiotics in clinical use, and achieving selective delivery of antibacterial cargos to pathogenic bacteria on the basis of siderophore receptor expression. PMID:28717471

[Antibiotics in the critically ill].

PubMed

Kolak, Radmila R

2010-01-01

Antibiotics are one the most common therapies administered in the intensive care unit setting. This review outlines the strategy for optimal use of antimicrobial agents in the critically ill. In severely ill patients, empirical antimicrobial therapy should be used when a suspected infection may impair the outcome. It is necessary to collect microbiological documentation before initiating empirical antimicrobial therapy. In addition to antimicrobial therapy, it is recommended to control a focus of infection and to modify factors that promote microbial growth or impair the host's antimicrobial defence. A judicious choice of antimicrobial therapy should be based on the host characteristics, the site of injection, the local ecology, and the pharmacokinetics/pharmacodynamics of antibiotics. This means treating empirically with broad-spectrum antimicrobials as soon as possible and narrowing the spectrum once the organism is identified (de-escalation), and limiting duration of therapy to the minimum effective period. Despite theoretical advantages, a combined antibiotic therapy is nor more effective than a mono-therapy in curing infections in most clinical trials involving intensive care patients. Nevertheless, textbooks and guidelines recommend a combination for specific pathogens and for infections commonly caused by these pathogens. Avoiding unnecessary antibiotic use and optimizing the administration of antimicrobial agents will improve patient outcomes while minimizing risks for the development of bacterial resistance. It is important to note that each intensive care unit should have a program in place which monitors antibiotic utilisation and its effectiveness. Only in this way can the impact of interventions aimed at improving antibiotic use be evaluated at the local level.

Preparation and characterization of soy protein films with a durable water resistance-adjustable and antimicrobial surface.

PubMed

Li, Shuzhao; Donner, Elizabeth; Xiao, Huining; Thompson, Michael; Zhang, Yachuan; Rempel, Curtis; Liu, Qiang

2016-12-01

A water resistant surface was first obtained by immobilizing hydrophobic copolymers, poly (styrene-co-glycidyl methacrylate) (PSG), with functional groups on soy protein isolate (SPI) films. XPS and AFM results showed that PSG copolymers were immobilized on the film by chemical bonding, and formed a rough surface with some bumps because of the segregation of two different phases on PSG copolymers. Water resistance of the modified films could be adjusted dramatically by further immobilizing different amounts of guanidine-based antimicrobial polymers, poly (hexamethylene guanidine hydrochloride) (PHMG) on the resulting hydrophobic surface. The introduction of hydrophilic PHMG on the resulting surface generated many micropores, which potentially increased the water uptake of the modified films. Furthermore, the modified SPI films showed higher thermostability compared to native SPI film and broad-spectrum antimicrobial activity by contact killing, attributed to the presence of PHMG on the surface. The modified SPI film with a multi-functional surface showed potential for applications in the packaging and medical fields. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Mode of action and membrane specificity of the antimicrobial peptide snakin-2

PubMed Central

Herbel, Vera

2016-01-01

Antimicrobial peptides (AMPs) are a diverse group of short, cationic peptides which are naturally occurring molecules in the first-line defense of most living organisms. They represent promising candidates for the treatment of pathogenic microorganisms. Snakin-2 (SN2) from tomato (Solanum lycopersicum) is stabilized through six intramolecular disulphide bridges; it shows broad-spectrum antimicrobial activity against bacteria and fungi, and it agglomerates single cells prior to killing. In this study, we further characterized SN2 by providing time-kill curves and corresponding growth inhibition analysis of model organisms, such as E. coli or B. subtilis. SN2 was produced recombinantly in E. coli with thioredoxin as fusion protein, which was removed after affinity purification by proteolytic digestion. Furthermore, the target specificity of SN2 was investigated by means of hemolysis and hemagglutination assays; its effect on plant cell membranes of isolated protoplasts was investigated by microscopy. SN2 shows a non-specific pore-forming effect in all tested membranes. We suggest that SN2 could be useful as a preservative agent to protect food, pharmaceuticals, or cosmetics from decomposition by microbes. PMID:27190708

Effects of clinical pathway implementation on antibiotic prescriptions for pediatric community-acquired pneumonia

PubMed Central

Zingarella, Silvia; Gastaldi, Andrea; Lundin, Rebecca; Perilongo, Giorgio; Frigo, Anna Chiara; Hamdy, Rana F.; Zaoutis, Theoklis; Da Dalt, Liviana; Giaquinto, Carlo

2018-01-01

Background Italian pediatric antimicrobial prescription rates are among the highest in Europe. As a first step in an Antimicrobial Stewardship Program, we implemented a Clinical Pathway (CP) for Community Acquired Pneumonia with the aim of decreasing overall prescription of antibiotics, especially broad-spectrum. Materials and methods The CP was implemented on 10/01/2015. We collected antibiotic prescribing and outcomes data from children aged 3 months-15 years diagnosed with CAP from 10/15/2014 to 04/15/2015 (pre-intervention period) and from 10/15/2015 to 04/15/2016 (post-intervention period). We assessed antibiotic prescription differences pre- and post-CP, including rates, breadth of spectrum, and duration of therapy. We also compared length of hospital stay for inpatients and treatment failure for inpatients and outpatients. Chi-square and Fisher’s exact test were used to compare categorical variables and Wilcoxon rank sum test was used to compare quantitative outcomes. Results 120 pre- and 86 post-intervention clinic visits were identified with a diagnosis of CAP. In outpatients, we observed a decrease in broad-spectrum regimens (50% pre-CP vs. 26.8% post-CP, p = 0.02), in particular macrolides, and an increase in narrow-spectrum (amoxicillin) post-CP. Post-CP children received fewer antibiotic courses (median DOT from 10 pre-CP to 8 post-CP, p<0.0001) for fewer days (median LOT from 10 pre-CP to 8 post-CP, p<0.0001) than their pre-CP counterparts. Physicians prescribed narrow-spectrum monotherapy more frequently than broad-spectrum combination therapy (DOT/LOT ratio 1.157 pre-CP vs. 1.065 post-CP). No difference in treatment failure was reported before and after implementation (2.3% pre-CP vs. 11.8% post-CP, p = 0.29). Among inpatients we also noted a decrease in broad-spectrum regimens (100% pre-CP vs. 66.7% post-CP, p = 0.02) and the introduction of narrow-spectrum regimens (0% pre-CP vs. 33.3% post-CP, p = 0.02) post-CP. Hospitalized patients received fewer antibiotic courses post-CP (median DOT from 18.5 pre-CP to 10 post-CP, p = 0.004), while there was no statistical difference in length of therapy (median LOT from 11 pre-CP to 10 post-CP, p = 0.06). Days of broad spectrum therapy were notably lower post-CP (median bsDOT from 17 pre-CP to 4.5 post-CP, p <0.0001). No difference in treatment failure was reported before and after CP implementation (16.7% pre-CP vs. 15.4% post-CP, p = 1). Conclusions Introduction of a CP for CAP in a Pediatric Emergency Department led to reduction of broad-spectrum antibiotic prescriptions, of combination therapy and of duration of treatment both for outpatients and inpatients. PMID:29489898

Optical control of antibacterial activity

NASA Astrophysics Data System (ADS)

Velema, Willem A.; van der Berg, Jan Pieter; Hansen, Mickel J.; Szymanski, Wiktor; Driessen, Arnold J. M.; Feringa, Ben L.

2013-11-01

Bacterial resistance is a major problem in the modern world, stemming in part from the build-up of antibiotics in the environment. Novel molecular approaches that enable an externally triggered increase in antibiotic activity with high spatiotemporal resolution and auto-inactivation are highly desirable. Here we report a responsive, broad-spectrum, antibacterial agent that can be temporally activated with light, whereupon it auto-inactivates on the scale of hours. The use of such a ‘smart’ antibiotic might prevent the build-up of active antimicrobial material in the environment. Reversible optical control over active drug concentration enables us to obtain pharmacodynamic information. Precisely localized control of activity is achieved, allowing the growth of bacteria to be confined to defined patterns, which has potential for the development of treatments that avoid interference with the endogenous microbial population in other parts of the organism.

Antimicrobial profile of Arthrobacter kerguelensis VL-RK_09 isolated from Mango orchards.

PubMed

Munaganti, Rajesh Kumar; Muvva, Vijayalakshmi; Konda, Saidulu; Naragani, Krishna; Mangamuri, Usha Kiranmayi; Dorigondla, Kumar Reddy; Akkewar, Dattatray M

An actinobacterial strain VL-RK_09 having potential antimicrobial activities was isolated from a mango orchard in Krishna District, Andhra Pradesh (India) and was identified as Arthrobacter kerguelensis. The strain A. kerguelensis VL-RK_09 exhibited a broad spectrum of in vitro antimicrobial activity against bacteria and fungi. Production of bioactive metabolites by the strain was the highest in modified yeast extract malt extract dextrose broth, as compared to other media tested. Lactose (1%) and peptone (0.5%) were found to be the most suitable carbon and nitrogen sources, respectively, for the optimum production of the bioactive metabolites. The maximum production of the bioactive metabolites was detected in the culture medium with an initial pH of 7, in which the strain was incubated for five days at 30°C under shaking conditions. Screening of secondary metabolites obtained from the culture broth led to the isolation of a compound active against a wide variety of Gram-positive and negative bacteria and fungi. The structure of the first active fraction was elucidated using Fourier transform infrared spectroscopy, electrospray ionization mass spectrometry, 1 H and 13 C nuclear magnetic resonance spectroscopy. The compound was identified as S,S-dipropyl carbonodithioate. This study is the first report of the occurrence of this compound in the genus Arthrobacter. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Antimicrobial Activity and Cell Selectivity of Synthetic and Biosynthetic Cationic Polymers

PubMed Central

Venkatesh, Mayandi; Barathi, Veluchamy Amutha; Goh, Eunice Tze Leng; Anggara, Raditya; Fazil, Mobashar Hussain Urf Turabe; Ng, Alice Jie Ying; Harini, Sriram; Aung, Thet Tun; Fox, Stephen John; Liu, Shouping; Barkham, Timothy Mark Sebastian; Loh, Xian Jun

2017-01-01

ABSTRACT The mammalian and microbial cell selectivity of synthetic and biosynthetic cationic polymers has been investigated. Among the polymers with peptide backbones, polymers containing amino side chains display greater antimicrobial activity than those with guanidine side chains, whereas ethylenimines display superior activity over allylamines. The biosynthetic polymer ε-polylysine (εPL) is noncytotoxic to primary human dermal fibroblasts at concentrations of up to 2,000 μg/ml, suggesting that the presence of an isopeptide backbone has greater cell selectivity than the presence of α-peptide backbones. Both εPL and linear polyethylenimine (LPEI) exhibit bactericidal properties by depolarizing the cytoplasmic membrane and disrupt preformed biofilms. εPL displays broad-spectrum antimicrobial properties against antibiotic-resistant Gram-negative and Gram-positive strains and fungi. εPL elicits rapid bactericidal activity against both Gram-negative and Gram-positive bacteria, and its biocompatibility index is superior to those of cationic antiseptic agents and LPEI. εPL does not interfere with the wound closure of injured rabbit corneas. In a rabbit model of bacterial keratitis, the topical application of εPL (0.3%, wt/vol) decreases the bacterial burden and severity of infections caused by Pseudomonas aeruginosa and Staphylococcus aureus strains. In vivo imaging studies confirm that εPL-treated corneas appeared transparent and nonedematous compared to untreated infected corneas. Taken together, our results highlight the potential of εPL in resolving topical microbial infections. PMID:28784676

An antibacterial and antiviral peptide produced by Enterococcus mundtii ST4V isolated from soya beans.

PubMed

Todorov, Svetoslav D; Wachsman, Mónica B; Knoetze, Hendriëtte; Meincken, Martina; Dicks, Leon M T

2005-06-01

Enterococcus mundtii ST4V, isolated from soya beans, produces a 3950Da antibacterial peptide active against Gram-positive and Gram-negative bacteria, including Enterococcus faecalis, Streptococcus spp., Pseudomonas aeruginosa, Klebsiella pneumoniae, Streptococcus pneumoniae and Staphylococcus aureus. The peptide also inactivated the herpes simplex viruses HSV-1 (strain F) and HSV-2 (strain G), a polio virus (PV3, strain Sabin) and a measles virus (strain MV/BRAZIL/001/91, an attenuated strain of MV). MV, HSV-1 and HSV-2 were 95.5%-99.9% inactivated by peptide ST4V at 400 microg/ml. Monkey kidney Vero cells were not inactivated, even at four times the level peptide ST4V displayed antiviral activity, indicating that the effect was not due to cytotoxicity. Complete inactivation or significant reduction in antimicrobial activity was observed after treatment of peptide ST4V with Proteinase K, pronase, pepsin and trypsin. No change in antimicrobial activity was recorded after treatment with alpha-amylase, suggesting that peptide ST4V was not glycosylated. This is the first description of an antibacterial and antiviral peptide with such broad-spectrum of activity, produced by a lactic acid bacterium.

Synthetic biology platform technologies for antimicrobial applications.

PubMed

Braff, Dana; Shis, David; Collins, James J

2016-10-01

The growing prevalence of antibiotic resistance calls for new approaches in the development of antimicrobial therapeutics. Likewise, improved diagnostic measures are essential in guiding the application of targeted therapies and preventing the evolution of therapeutic resistance. Discovery platforms are also needed to form new treatment strategies and identify novel antimicrobial agents. By applying engineering principles to molecular biology, synthetic biologists have developed platforms that improve upon, supplement, and will perhaps supplant traditional broad-spectrum antibiotics. Efforts in engineering bacteriophages and synthetic probiotics demonstrate targeted antimicrobial approaches that can be fine-tuned using synthetic biology-derived principles. Further, the development of paper-based, cell-free expression systems holds promise in promoting the clinical translation of molecular biology tools for diagnostic purposes. In this review, we highlight emerging synthetic biology platform technologies that are geared toward the generation of new antimicrobial therapies, diagnostics, and discovery channels. Copyright © 2016 Elsevier B.V. All rights reserved.

How to educate prescribers in antimicrobial stewardship practices

PubMed Central

Pulcini, Céline; Gyssens, Inge C.

2013-01-01

Widespread antimicrobial use has compromised its value, leading to a crisis of antimicrobial resistance. A major cause of misuse is insufficient knowledge of prescribing of antimicrobials in many categories of professionals. An important principle of antimicrobial stewardship is avoiding selection pressure in the patient, both on pathogen and commensal by avoiding unnecessary use, choosing the least broad-spectrum antibiotic, adequate doses, a good timing and the shortest possible duration. Up to now, most educational efforts have been targeted at professionals (mostly medical doctors) after their training and at the adult public. In the past few years, progress has been made in educating children. It is now crucial that academia and ministries of Health and Education jointly focus on an adapted undergraduate medical/professional curriculum that teaches all necessary principles of microbiology, infectious diseases and clinical pharmacology, with emphasis on the principles of prudent prescribing. PMID:23361336

Ciprofloxacin prophylaxis delays initiation of broad-spectrum antibiotic therapy and reduces the overall use of antimicrobial agents during induction therapy for acute leukaemia: A single-centre study.

PubMed

Hallböök, Helene; Lidström, Anna-Karin; Pauksens, Karlis

2016-01-01

Due to an outbreak of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae, the routine use of fluoroquinolone prophylaxis was questioned. As a result, this study was conducted with the aim to evaluate the impact of ciprofloxacin-prophylaxis on the use of broad-spectrum antibioctics and anti-mycotics. A cohort of 139 consecutive patients with acute leukaemia treated with remission-inducing induction chemotherapy between 2004-2012 at the Department of Haematology in Uppsala University Hospital was analysed. Fifty-three patients (38%) received broad-spectrum antibiotics at the initiation of chemotherapy and were not eligible for prophylaxis. Of the remaining patients, the initiation of broad-spectrum antibiotics was delayed by 3 days in those receiving ciprofloxacin prophylaxis (n = 47) compared with those receiving no prophylaxis (n = 39). The median duration of systemic antibiotic treatment was 6 days shorter in patients receiving ciprofloxacin prophylaxis (12 vs 18 days; p = 0.0005) and the cumulative (total) median days on systemic antibiotic treatment was shortened by 8 days (15 vs 23 days, p = 0.0008). Piperacillin/tazobactam (p = 0.02), carbapenems (p = 0.05) and empiric broad-spectrum antifungals (p < 0.01) were used significantly less often when ciprofloxacin prophylaxis was given. Ciprofloxacin prophylaxis delayed empiric therapy by 3 days and reduced overall antibiotic use in this study. These benefits must be evaluated vs the risks of development of resistant bacterial strains, making fluoroquinolone prophylaxis an open question for debate.

The preliminary assessment of anti-microbial activity of HPLC separated components of Kirkia wilmsii.

PubMed

Chigayo, K; Mojapelo, P E L; Bessong, P; Gumbo, J R

2014-01-01

Most communities in developing countries rely on traditional medicines for the treatment of diseases. In South Africa, the Limpopo province, within the Lebowakgomo district, uses tuberous roots of Kirkia wilmsii, after infusion in water for the treatment of a wide range of diseases by Sotho communities. The main objective of the study was to assess the anti-microbial activity of separated aqueous components of the Kirkia wilmsii tuberous roots. The clear aqueous extracts that were obtained after a 0.45 µm membrane filtration (Millipore Millex-HV Hydrophillic PVDF filter), were then injected into a preparative high performance liquid chromatography instrument in which pure components, as shown by peaks, were collected and evaluated for anti-microbial activity against a range of microorganisms. The eight separated components were obtained, out of which four components showed anti-microbial activity (AMA). The freeze dried components were re-dissolved in deionised water and then evaluated for AMA against Vibrio cholerae, Shigella dysenteriae, Aeromonas hydrophilia, Salmonella typhi Proteus mirabilis, Escherichia coli, Staphylococcus aureus, Candida albicans and Enterobacter aerogenes. Component one exhibited antimicrobial activity against Shigella dysenteriae, Aeromonas hydrophilia, Salmonella typhi, Proteus mirabilis, Escherichia coli and Staphylococcus aureus with a minimum inhibitory concentration (MIC), of 3.445 mg/ml. Component five was only active against Proteus mirabilis with a MIC of 0.08 mg/ml. Component 7, was active against Shigella dysenteriae, Staphylococcus aureus and Escherichia coli with a MIC of 0.365 mg/ml against both Shigella dysenteriae and Staphylococcus aureus and 0.091 mg/ml against Escherichia coli. Component 8, was active against Shigella, Aeromonas hydrophilia, Salmonella, Proteus mirabilis, Escherichia coli with a MIC of 155 mg/ml. Only four out of eight aqueous extracts showed AMA against both gram negative and positive bacteria and showed no AMA against Candida albicans, Enterobacter aerogenes and Vibrio cholerae. Therefore the Kirkia wilmsii plant root may be used as a broad spectrum antibiotic.

Copper and Quaternary Ammonium Cations Exert Synergistic Bactericidal and Antibiofilm Activity against Pseudomonas aeruginosa▿

PubMed Central

Harrison, Joe J.; Turner, Raymond J.; Joo, Daniel A.; Stan, Michelle A.; Chan, Catherine S.; Allan, Nick D.; Vrionis, Helen A.; Olson, Merle E.; Ceri, Howard

2008-01-01

Biofilms are slimy aggregates of microbes that are likely responsible for many chronic infections as well as for contamination of clinical and industrial environments. Pseudomonas aeruginosa is a prevalent hospital pathogen that is well known for its ability to form biofilms that are recalcitrant to many different antimicrobial treatments. We have devised a high-throughput method for testing combinations of antimicrobials for synergistic activity against biofilms, including those formed by P. aeruginosa. This approach was used to look for changes in biofilm susceptibility to various biocides when these agents were combined with metal ions. This process identified that Cu2+ works synergistically with quaternary ammonium compounds (QACs; specifically benzalkonium chloride, cetalkonium chloride, cetylpyridinium chloride, myristalkonium chloride, and Polycide) to kill P. aeruginosa biofilms. In some cases, adding Cu2+ to QACs resulted in a 128-fold decrease in the biofilm minimum bactericidal concentration compared to that for single-agent treatments. In combination, these agents retained broad-spectrum antimicrobial activity that also eradicated biofilms of Escherichia coli, Staphylococcus aureus, Salmonella enterica serovar Cholerasuis, and Pseudomonas fluorescens. To investigate the mechanism of action, isothermal titration calorimetry was used to show that Cu2+ and QACs do not interact in aqueous solutions, suggesting that each agent exerts microbiological toxicity through independent biochemical routes. Additionally, Cu2+ and QACs, both alone and in combination, reduced the activity of nitrate reductases, which are enzymes that are important for normal biofilm growth. Collectively, the results of this study indicate that Cu2+ and QACs are effective combinations of antimicrobials that may be used to kill bacterial biofilms. PMID:18519726

Methods for attaching polymerizable ceragenins to water treatment membranes using amine and amide linkages

DOEpatents

Hibbs, Michael; Altman, Susan J.; Jones, Howland D.T.; Savage, Paul B.

2013-10-15

This invention relates to methods for chemically grafting and attaching ceragenin molecules to polymer substrates; methods for synthesizing ceragenin-containing copolymers; methods for making ceragenin-modified water treatment membranes and spacers; and methods of treating contaminated water using ceragenin-modified treatment membranes and spacers. Ceragenins are synthetically produced antimicrobial peptide mimics that display broad-spectrum bactericidal activity. Alkene-functionalized ceragenins (e.g., acrylamide-functionalized ceragenins) can be attached to polyamide reverse osmosis membranes using amine-linking, amide-linking, UV-grafting, or silane-coating methods. In addition, silane-functionalized ceragenins can be directly attached to polymer surfaces that have free hydroxyls.

Methods for attaching polymerizable ceragenins to water treatment membranes using silane linkages

DOEpatents

Hibbs, Michael; Altman, Susan J.; Jones, Howland D. T.; Savage, Paul B.

2013-09-10

This invention relates to methods for chemically grafting and attaching ceragenin molecules to polymer substrates; methods for synthesizing ceragenin-containing copolymers; methods for making ceragenin-modified water treatment membranes and spacers; and methods of treating contaminated water using ceragenin-modified treatment membranes and spacers. Ceragenins are synthetically produced antimicrobial peptide mimics that display broad-spectrum bactericidal activity. Alkene-functionalized ceragenins (e.g., acrylamide-functionalized ceragenins) can be attached to polyamide reverse osmosis membranes using amine-linking, amide-linking, UV-grafting, or silane-coating methods. In addition, silane-functionalized ceragenins can be directly attached to polymer surfaces that have free hydroxyls.

The recent progress of isoxazole in medicinal chemistry.

PubMed

Zhu, Jie; Mo, Jun; Lin, Hong-Zhi; Chen, Yao; Sun, Hao-Peng

2018-05-28

Isoxazole compounds exhibit a wide spectrum of targets and broad biological activities. Developing compounds with heterocycle rings has been one of the trends. The integration of isoxazole ring can offer improved physical-chemical properties. Because of the unique profiles, isoxazole ring becomes a popular moiety in compounds design. In this review article, the major focus has been paid to the applications of isoxazole compounds in treating multiple diseases, including anticancer, antimicrobial, anti-inflammatory, etc. Strategies for compounds design for preclinical, clinical, and FDA approved drugs were discussed. Also, the emphasis has been addressed to the future perspectives and trend for the application. Copyright © 2018 Elsevier Ltd. All rights reserved.

The antibacterial peptide ABP-CM4: the current state of its production and applications.

PubMed

Li, Jian Feng; Zhang, Jie; Xu, Xing Zhou; Han, Yang Yang; Cui, Xian Wei; Chen, Yu Qing; Zhang, Shuang Quan

2012-06-01

The increasing resistance of bacteria and fungi to currently available antibiotics is a major concern worldwide, leading to enormous efforts to develop new antibiotics with new modes of actions. Antibacterial peptide CM4 (ABP-CM4) is a small cationic peptide with broad-spectrum activities against bacteria, fungi, and tumor cells, which may possibly be used as a promising candidate for a new antibiotic. For pharmaceutical applications, a large quantity of antimicrobial peptides needs to be produced economically. In this communication, the progress in the structural characteristics, heterologous production, and biological evaluation of ABP-CM4 are reviewed.

Antimicrobial utilization and bacterial resistance at three different hospitals.

PubMed

Vlahović-Palcevski, V; Morović, M; Palcevski, G; Betica-Radić, L

2001-01-01

It has been generally recognized that the prevalence of bacterial resistance among bacteria is an unavoidable consequence of antibiotic use and is positively linked to the overall use of antibacterial drugs. The purpose of this study was to investigate the extent of antimicrobial usage and to evaluate the antimicrobial resistance at three different hospital settings in Croatia: a clinical hospital, a general hospital and a specialized clinic for infectious diseases. In this survey the antimicrobial drug consumption and antimicrobial susceptibility test results were analyzed for the first 6 months of 1997 in three different hospitals in Croatia: the University Hospital Center (UHC), Rijeka, the Clinic for Infectious Diseases 'Dr Fran Mihaljević', Zagreb and the Dubrovnik General Hospital. The data were collected from corresponding hospital pharmacy records and microbiology laboratories. Antimicrobial drug utilization was expressed in number of defined daily doses (DDDs) per 100 bed days. High antimicrobial utilization and high resistance rates were found in all three hospitals. At the Clinic for Infectious Diseases, the most frequently used antimicrobials where those of narrow spectrum while at the UHC Rijeka and the Dubrovnik General Hospital the broad spectrum antimicrobials were mostly used. The highest antimicrobial consumption was noted at the Susak locality of the UHC, Rijeka, where the highest resistance rates of bacteria to antimicrobials were also found. Results of this observational study indicate that attempts should be made to reduce the influence of factors that may lead to emergent resistance. The most effective approach to the prevention of transmission of multidrug-resistant pathogens is preventing the initial emergence of resistance. A rational and strict antibiotic policy is thus of great importance for the optimal use of these agents.

Antimicrobial Activity of 8-Quinolinols, Salicylic Acids, Hydroxynaphthoic Acids, and Salts of Selected Quinolinols with Selected Hydroxy-Acids

PubMed Central

Gershon, Herman; Parmegiani, Raulo

1962-01-01

Seventy-seven compounds were screened by the disc-plate method against strains of five bacteria and five fungi. A new constant was proposed to describe the antimicrobial activity of a compound in a defined system of organisms. This constant includes not only the inhibitory level of activity of the material but also the number of organisms inhibited. This constant, the antimicrobial spectrum index, was compared with the antimicrobial index of Albert. PMID:13898066

New Potent Membrane-Targeting Antibacterial Peptides from Viral Capsid Proteins

PubMed Central

Dias, Susana A.; Freire, João M.; Pérez-Peinado, Clara; Domingues, Marco M.; Gaspar, Diana; Vale, Nuno; Gomes, Paula; Andreu, David; Henriques, Sónia T.; Castanho, Miguel A. R. B.; Veiga, Ana S.

2017-01-01

The increasing prevalence of multidrug-resistant bacteria urges the development of new antibacterial agents. With a broad spectrum activity, antimicrobial peptides have been considered potential antibacterial drug leads. Using bioinformatic tools we have previously shown that viral structural proteins are a rich source for new bioactive peptide sequences, namely antimicrobial and cell-penetrating peptides. Here, we test the efficacy and mechanism of action of the most promising peptides among those previously identified against both Gram-positive and Gram-negative bacteria. Two cell-penetrating peptides, vCPP 0769 and vCPP 2319, have high antibacterial activity against Staphylococcus aureus, MRSA, Escherichia coli, and Pseudomonas aeruginosa, being thus multifunctional. The antibacterial mechanism of action of the two most active viral protein-derived peptides, vAMP 059 and vCPP 2319, was studied in detail. Both peptides act on both Gram-positive S. aureus and Gram-negative P. aeruginosa, with bacterial cell death occurring within minutes. Also, these peptides cause bacterial membrane permeabilization and damage of the bacterial envelope of P. aeruginosa cells. Overall, the results show that structural viral proteins are an abundant source for membrane-active peptides sequences with strong antibacterial properties. PMID:28522994

Anticancer activities of bovine and human lactoferricin-derived peptides.

PubMed

Arias, Mauricio; Hilchie, Ashley L; Haney, Evan F; Bolscher, Jan G M; Hyndman, M Eric; Hancock, Robert E W; Vogel, Hans J

2017-02-01

Lactoferrin (LF) is a mammalian host defense glycoprotein with diverse biological activities. Peptides derived from the cationic region of LF possess cytotoxic activity against cancer cells in vitro and in vivo. Bovine lactoferricin (LFcinB), a peptide derived from bovine LF (bLF), exhibits broad-spectrum anticancer activity, while a similar peptide derived from human LF (hLF) is not as active. In this work, several peptides derived from the N-terminal regions of bLF and hLF were studied for their anticancer activities against leukemia and breast-cancer cells, as well as normal peripheral blood mononuclear cells. The cyclized LFcinB-CLICK peptide, which possesses a stable triazole linkage, showed improved anticancer activity, while short peptides hLF11 and bLF10 were not cytotoxic to cancer cells. Interestingly, hLF11 can act as a cell-penetrating peptide; when combined with the antimicrobial core sequence of LFcinB (RRWQWR) through either a Pro or Gly-Gly linker, toxicity to Jurkat cells increased. Together, our work extends the library of LF-derived peptides tested for anticancer activity, and identified new chimeric peptides with high cytotoxicity towards cancerous cells. Additionally, these results support the notion that short cell-penetrating peptides and antimicrobial peptides can be combined to create new adducts with increased potency.

Anti-infective therapeutics from the Lepidopteran model host Galleria mellonella.

PubMed

Vilcinskas, Andreas

2011-01-01

The larvae of the greater wax moth Galleria mellonella prosper in use both as surrogate alternative model hosts for human pathogens and as a whole-animal-high-throughput-system for in vivo testing of antibiotics or mutant-libraries of pathogens. In addition, a broad spectrum of antimicrobial peptides and proteins has been identified in this insect during past decade among which some appear to be specific for Lepidoptera. Its arsenal of immunity-related effector molecules encompasses peptides and proteins exhibiting potent activity against bacteria, fungi or both, whose potential as new anti-infective therapeutics are presently being explored. Of particular interest is the insect metalloproteinase inhibitor (IMPI) which has been discovered in G. mellonella. The IMPI exhibits a specific and potent activity against thermolysin-like microbial metalloproteinases including a number of prominent virulence and/or pathogenic factors of human pathogens which are responsible for severe symptoms such as septicemia, hemorrhagic tissue bleeding, necrosis and enhancement of vascular permeability. The IMPI and antimicrobial peptides from G. mellonella may provide promising templates for the rational design of new drugs since evidence is available that the combination of antibiotics with inhibitors of pathogen-associated proteolytic enzymes yields synergistic therapeutic effects. The potential and limitations of insect-derived gene-encoded antimicrobial compounds as anti-infective therapeutics are discussed.

Human host defense peptides - role in maintaining human homeostasis and pathological processes.

PubMed

Dawgul, Malgorzata Anna; Greber, Katarzyna Ewa; Sawicki, Wieslaw; Kamysz, Wojciech

2016-12-12

The human body expresses over 100 host defense peptides and proteins (antimicrobial peptides, AMPs). The compounds are produced by tissues and mucosal surfaces, e.g. skin, the digestive and urinary tract, the ocular surface and neutrophils, and are believed to play a crucial role in defense from microbial infection. They are considered to protect the human body against microbial infections due to their antimicrobial and immunomodulatory activities. As well as having strong antimicrobial activity towards a broad spectrum of microorganisms, AMPs have been found to interact with neutrophils, monocytes and T-cells and promote the production of cytokines. They also neutralize the action of lipopolysaccharide (LPS) and play a crucial role in wound healing processes. In response to the microbial stimuli the AMPs are released in order to fight the infection, however there are several microorganisms evading the human immune system by downregulation of AMPs. Decreased or elevated expression of AMPs is associated also with several non-infectious diseases. Despite numerous studies conducted in the field of AMPs over the last few decades, their exact role in physiological and pathological processes remains to be explained. In this paper, we review the most significant human AMPs and their potential roles in maintaining human homeostasis as well as in pathological processes.

Genetic modification of potato against microbial diseases: in vitro and in planta activity of a dermaseptin B1 derivative, MsrA2.

PubMed

Osusky, Milan; Osuska, Lubica; Kay, William; Misra, Santosh

2005-08-01

Dermaseptin B1 is a potent cationic antimicrobial peptide found in skin secretions of the arboreal frog Phyllomedusa bicolor. A synthetic derivative of dermaseptin B1, MsrA2 (N-Met-dermaseptin B1), elicited strong antimicrobial activities against various phytopathogenic fungi and bacteria in vitro. To assess its potential for plant protection, MsrA2 was expressed at low levels (1-5 microg/g of fresh tissue) in the transgenic potato (Solanum tuberosum L.) cv. Desiree. Stringent challenges of these transgenic potato plants with a variety of highly virulent fungal phytopathogens--Alternaria, Cercospora, Fusarium, Phytophthora, Pythium, Rhizoctonia and Verticillium species--and with the bacterial pathogen Erwinia carotovora demonstrated that the plants had an unusually broad-spectrum and powerful resistance to infection. MsrA2 profoundly protected both plants and tubers from diseases such as late blight, dry rot and pink rot and markedly extended the storage life of tubers. Due to these properties in planta, MsrA2 is proposed as an ideal antimicrobial peptide candidate to significantly increase resistance to phytopathogens and improve quality in a variety of crops worldwide with the potential to obviate fungicides and facilitate storage under difficult conditions.

Potential Applications of the Cyclic Peptide Enterocin AS-48 in the Preservation of Vegetable Foods and Beverages.

PubMed

Abriouel, Hikmate; Lucas, Rosario; Omar, Nabil Ben; Valdivia, Eva; Gálvez, Antonio

2010-06-01

Bacteriocins are antimicrobial peptides produced by bacteria. Among them, the enterococcal bacteriocin (enterocin) AS-48 stands for its peculiar characteristics and broad-spectrum antimicrobial activity. AS-48 belongs to the class of circular bacteriocins and has been studied in depth in several aspects: peptide structure, genetic determinants, and mode of action. Recently, a wealth of knowledge has accumulated on the antibacterial activity of this bacteriocin against foodborne pathogenic and spoilage bacteria in food systems, especially in vegetable foods and drinks. This work provides a general overview on the results from tests carried out with AS-48 in different vegetable food categories (such as fruit juices, ciders, sport and energy drinks, fresh fruits and vegetables, pre-cooked ready to eat foods, canned vegetables, and bakery products). Depending on the food substrate, the bacteriocin has been tested alone or as part of hurdle technology, in combination with physico-chemical treatments (such as mild heat treatments or high-intensity pulsed electric fields) and other antimicrobial substances (such as essential oils, phenolic compounds, and chemical preservatives). Since the work carried out on bacteriocins in preservation of vegetable foods and drinks is much more limited compared to meat and dairy products, the results reported for AS-48 may open new possibilities in the field of bacteriocin applications.

Characterisation of non-autoinducing tropodithietic Acid (TDA) production from marine sponge Pseudovibrio species.

PubMed

Harrington, Catriona; Reen, F Jerry; Mooij, Marlies J; Stewart, Fiona A; Chabot, Jean-Baptiste; Guerra, Antonio F; Glöckner, Frank O; Nielsen, Kristian F; Gram, Lone; Dobson, Alan D W; Adams, Claire; O'Gara, Fergal

2014-12-10

The search for new antimicrobial compounds has gained added momentum in recent years, paralleled by the exponential rise in resistance to most known classes of current antibiotics. While modifications of existing drugs have brought some limited clinical success, there remains a critical need for new classes of antimicrobial compound to which key clinical pathogens will be naive. This has provided the context and impetus to marine biodiscovery programmes that seek to isolate and characterize new activities from the aquatic ecosystem. One new antibiotic to emerge from these initiatives is the antibacterial compound tropodithietic acid (TDA). The aim of this study was to provide insight into the bioactivity of and the factors governing the production of TDA in marine Pseudovibrio isolates from a collection of marine sponges. The TDA produced by these Pseudovibrio isolates exhibited potent antimicrobial activity against a broad spectrum of clinical pathogens, while TDA tolerance was frequent in non-TDA producing marine isolates. Comparative genomics analysis suggested a high degree of conservation among the tda biosynthetic clusters while expression studies revealed coordinated regulation of TDA synthesis upon transition from log to stationary phase growth, which was not induced by TDA itself or by the presence of the C10-acyl homoserine lactone quorum sensing signal molecule.

Characterisation of Non-Autoinducing Tropodithietic Acid (TDA) Production from Marine Sponge Pseudovibrio Species

PubMed Central

Harrington, Catriona; Reen, F. Jerry; Mooij, Marlies J.; Stewart, Fiona A.; Chabot, Jean-Baptiste; Guerra, Antonio F.; Glöckner, Frank O.; Nielsen, Kristian F.; Gram, Lone; Dobson, Alan D. W.; Adams, Claire; O’Gara, Fergal

2014-01-01

The search for new antimicrobial compounds has gained added momentum in recent years, paralleled by the exponential rise in resistance to most known classes of current antibiotics. While modifications of existing drugs have brought some limited clinical success, there remains a critical need for new classes of antimicrobial compound to which key clinical pathogens will be naive. This has provided the context and impetus to marine biodiscovery programmes that seek to isolate and characterize new activities from the aquatic ecosystem. One new antibiotic to emerge from these initiatives is the antibacterial compound tropodithietic acid (TDA). The aim of this study was to provide insight into the bioactivity of and the factors governing the production of TDA in marine Pseudovibrio isolates from a collection of marine sponges. The TDA produced by these Pseudovibrio isolates exhibited potent antimicrobial activity against a broad spectrum of clinical pathogens, while TDA tolerance was frequent in non-TDA producing marine isolates. Comparative genomics analysis suggested a high degree of conservation among the tda biosynthetic clusters while expression studies revealed coordinated regulation of TDA synthesis upon transition from log to stationary phase growth, which was not induced by TDA itself or by the presence of the C10-acyl homoserine lactone quorum sensing signal molecule. PMID:25513851

Multivalent Antimicrobial Polymer Nanoparticles Target Mycobacteria and Gram-Negative Bacteria by Distinct Mechanisms

PubMed Central

2017-01-01

Because of the emergence of antimicrobial resistance to traditional small-molecule drugs, cationic antimicrobial polymers are appealing targets. Mycobacterium tuberculosis is a particular problem, with multi- and total drug resistance spreading and more than a billion latent infections globally. This study reports nanoparticles bearing variable densities of poly(dimethylaminoethyl methacrylate) and the unexpected and distinct mechanisms of action this multivalent presentation imparts against Escherichia coli versus Mycobacterium smegmatis (model of M. tuberculosis), leading to killing or growth inhibition, respectively. A convergent “grafting to” synthetic strategy was used to assemble a 50-member nanoparticle library, and using a high-throughput screen identified that only the smallest (2 nm) particles were stable in both saline and complex cell media. Compared with the linear polymers, the nanoparticles displayed two- and eight-fold enhancements in antimicrobial activity against M. smegmatis and E. coli, respectively. Mechanistic studies demonstrated that the antimicrobial particles were bactericidal against E. coli due to rapid disruption of the cell membranes. Conversely, against M. smegmatis the particles did not lyse the cell membrane but rather had a bacteriostatic effect. These results demonstrate that to develop new polymeric antituberculars the widely assumed, broad spectrum, membrane-disrupting mechanism of polycations must be re-evaluated. It is clear that synthetic nanomaterials can engage in more complex interactions with mycobacteria, which we hypothesize is due to the unique cell envelope at the surface of these bacteria. PMID:29195272

Structure-activity modelling of essential oils, their components, and key molecular parameters and descriptors.

PubMed

Owen, Lucy; Laird, Katie; Wilson, Philippe B

2018-04-01

Many essential oil components are known to possess broad spectrum antimicrobial activity, including against antibiotic resistant bacteria. These compounds may be a useful source of new and novel antimicrobials. However, there is limited research on the structure-activity relationship (SAR) of essential oil compounds, which is important for target identification and lead optimization. This study aimed to elucidate SARs of essential oil components from experimental and literature sources. Minimum Inhibitory Concentrations (MICs) of essential oil components were determined against Escherichia coli and Staphylococcus aureus using a microdilution method and then compared to those in published in literature. Of 12 essential oil components tested, carvacrol and cuminaldehyde were most potent with MICs of 1.98 and 2.10 mM, respectively. The activity of 21 compounds obtained from the literature, MICs ranged from 0.004 mM for limonene to 36.18 mM for α-terpineol. A 3D qualitative SAR model was generated from MICs using FORGE software by consideration of electrostatic and steric parameters. An r 2 value of 0.807 for training and cross-validation sets was achieved with the model developed. Ligand efficiency was found to correlate well to the observed activity (r 2  = 0.792), while strongly negative electrostatic regions were present in potent molecules. These descriptors may be useful for target identification of essential oils or their major components in antimicrobial/drug development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sensitization of Staphylococcus aureus to methicillin and other antibiotics in vitro and in vivo in the presence of HAMLET.

PubMed

Marks, Laura R; Clementi, Emily A; Hakansson, Anders P

2013-01-01

HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a protein-lipid complex from human milk with both tumoricidal and bactericidal activities. HAMLET exerts a rather specific bactericidal activity against some respiratory pathogens, with highest activity against Streptococcus pneumoniae, but lacks activity against most other bacterial pathogens, including Staphylococci. Still, ion transport associated with death in S. pneumoniae is also detected to a lower degree in insensitive organisms. In this study we demonstrate that HAMLET acts as an antimicrobial adjuvant that can increase the activity of a broad spectrum of antibiotics (methicillin, vancomycin, gentamicin and erythromycin) against multi-drug resistant Staphylococcus aureus, to a degree where they become sensitive to those same antibiotics, both in antimicrobial assays against planktonic and biofilm bacteria and in an in vivo model of nasopharyngeal colonization. We show that HAMLET exerts these effects specifically by dissipating the proton gradient and inducing a sodium-dependent calcium influx that partially depolarizes the plasma membrane, the same mechanism induced during pneumococcal death. These effects results in an increased cell associated binding and/or uptake of penicillin, gentamicin and vancomycin, especially in resistant stains. Finally, HAMLET inhibits the increased resistance of methicillin seen under antibiotic pressure and the bacteria do not become resistant to the adjuvant, which is a major advantageous feature of the molecule. These results highlight HAMLET as a novel antimicrobial adjuvant with the potential to increase the clinical usefulness of antibiotics against drug resistant strains of S. aureus.

In Vitro Antimicrobial Activity of Razupenem (SMP-601, PTZ601) against Anaerobic Bacteria▿

PubMed Central

Tran, Chau Minh; Tanaka, Kaori; Yamagishi, Yuka; Goto, Takatsugu; Mikamo, Hiroshige; Watanabe, Kunitomo

2011-01-01

We evaluated the in vitro antianaerobic activity of razupenem (SMP-601, PTZ601), a new parenterally administered carbapenem, against 70 reference strains and 323 clinical isolates. Razupenem exhibited broad-spectrum activity against anaerobes, inhibiting most of the reference strains when used at a concentration of ≤1 μg/ml. Furthermore, it exhibited strong activity, comparable to those of other carbapenems (meropenem and doripenem), against clinically isolated non-fragilis Bacteroides spp. (MIC90s of 2 μg/ml), with MIC90 values of 0.06, 0.03, and 0.5 μg/ml against Prevotella spp., Porphyromonas spp., and Fusobacterium spp., respectively. Clinical isolates of anaerobic Gram-positive cocci, Eggerthella spp., and Clostridium spp. were highly susceptible to razupenem (MIC90s, 0.03 to 1 μg/ml). PMID:21343447

Antimicrobial peptides expressed in medicinal maggots of the blow fly Lucilia sericata show combinatorial activity against bacteria.

PubMed

Pöppel, Anne-Kathrin; Vogel, Heiko; Wiesner, Jochen; Vilcinskas, Andreas

2015-05-01

The larvae of the common green bottle fly (Lucilia sericata) produce antibacterial secretions that have a therapeutic effect on chronic and nonhealing wounds. Recent developments in insect biotechnology have made it possible to use these larvae as a source of novel anti-infectives. Here, we report the application of next-generation RNA sequencing (RNA-Seq) to characterize the transcriptomes of the larval glands, crop, and gut, which contribute to the synthesis of antimicrobial peptides (AMPs) and proteins secreted into wounds. Our data confirm that L. sericata larvae have adapted in order to colonize microbially contaminated habitats, such as carrion and necrotic wounds, and are protected against infection by a diverse spectrum of AMPs. L. sericata AMPs include not only lucifensin and lucimycin but also novel attacins, cecropins, diptericins, proline-rich peptides, and sarcotoxins. We identified 47 genes encoding putative AMPs and produced 23 as synthetic analogs, among which some displayed activities against a broad spectrum of microbial pathogens, including Pseudomonas aeruginosa, Proteus vulgaris, and Enterococcus faecalis. Against Escherichia coli (Gram negative) and Micrococcus luteus (Gram positive), we found mostly additive effects but also synergistic activity when selected AMPs were tested in combination. The AMPs that are easy to synthesize are currently being produced in bulk to allow their evaluation as novel anti-infectives that can be formulated in hydrogels to produce therapeutic wound dressings and adhesive bandages. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

A New Synthetic Peptide with In vitro Antibacterial Potential Against Escherichia coli O157:H7 and Methicillin-Resistant Staphylococcus aureus (MRSA).

PubMed

Prada, Y A; Guzmán, F; Rondón, P; Escobar, P; Ortíz, C; Sierra, D A; Torres, R; Mejía-Ospino, E

2016-09-01

In this work, we performed the rational design of a cationic antimicrobial peptide, GIBIMPY4, using the software DEPRAMPs developed at the GIBIM research group. GIBIMPY4 has a length of 17 amino acids, it is amphipathic, its structure is α-helix and it has a net charge of (+5). Solid-phase peptide synthesis was performed using the Fmoc strategy in acid medium. The primary structure was confirmed by MALDI-TOF mass spectrometry. The antimicrobial activity of the peptide was evaluated by broth microdilution method by measuring optical density in 96-well microplates. The minimal inhibitory concentration of GIBIMPY4 to kill 50 % of the bacterial cells (MIC50) was 6.20 ± 0.02 µM for MRSA and 4.55 ± 0.02 µM for E. coli O157:H7, while also reporting a bacteriostatic effect for the later. GIBIMPY4 activity was sensitive to salt concentration in E. coli but insignificant effect in its activity against MRSA. The peptide seems to be a broad-spectrum antimicrobial agent based on the results against Gram-positive and Gram-negative bacteria and was specific for bacterial cells E. coli O157:H7 with index of specificity equal to 9.01 in vitro assays.

Recent approaches in food bio-preservation - a review

PubMed Central

Singh, Veer Pal

2018-01-01

Bio-preservation is a technique of extending the shelf life of food by using natural or controlled microbiota or antimicrobials. The fermentation products as well as beneficial bacteria are generally selected in this process to control spoilage and render pathogen inactive. The special interest organism or central organism used for this purpose is lactic acid bacteria (LAB) and their metabolites. They are capable to exhibit antimicrobial properties and helpful in imparting unique flavour and texture to the food products. The major compounds produced by LAB are bacteriocin, organic acids and hydrogen peroxide. Bacteriocin is peptides or proteins with antimicrobial activity. On the basis of size, structure and post-translational modification, bacteriocin is divided into four different classes. Due to non-toxic, non-immunogenic, thermo-resistance characteristics and broad bactericidal activity, LAB bacteriocins are considered good bio-preservative agents. The most common LAB bactriocin is nisin which has wider applications in food industry and has been Food and Drug Administration (FDA) approved. Nisin and other bacteriocin are being used in vegetables products, dairy and meat industries. Apart from LAB metabolites, bacteriophages and endolysins has promising role in food processing, preservation and safety. Bacteriocins and endolysins are more suitable for DNA shuffling and protein engineering to generate highly potent variants with expanded activity spectrum. Genetically modified bacteriophages may also be helpful in bio-preservation, however; their safety issues must be addressed properly before selection as bio-preservative agent. PMID:29721439

Phyllanthus wightianus Müll. Arg.: A Potential Source for Natural Antimicrobial Agents

PubMed Central

Natarajan, D.; Srinivasan, R.; Shivakumar, M. S.

2014-01-01

Phyllanthus wightianus belongs to Euphorbiaceae family having ethnobotanical importance. The present study deals with validating the antimicrobial potential of solvent leaf extracts of P. wightianus. 11 human bacterial pathogens (Bacillus subtilis, Streptococcus pneumoniae, Staphylococcus epidermidis, Proteus vulgaris, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhimurium, Escherichia coli, Shigella flexneri, Proteus vulgaris, and Serratia marcescens) and 4 fungal pathogens (Candida albicans, Cryptococcus neoformans, Mucor racemosus, and Aspergillus niger) were also challenged with solvent leaf extracts usingagar well and disc diffusion methods. Further, identification of the active component present in the bioactive extract was done using GC-MS analysis. Results show that all extracts exhibited broad spectrum (6–29 mm) of antibacterial activity on most of the tested organisms. The results highlight the fact that the well in agar method was more effective than disc diffusion method. Significant antimicrobial activity was detected in methanol extract against S. pneumoniae (29 mm) with MIC and MBC values of 15.62 μg/mL. GC-MS analysis revealed that 29 bioactive constituents were present in methanolic extract of P. wightianus, of which 9,12-octadecaenioic acid (peak area 22.82%; RT-23.97) and N-hexadecanoic acid (peak area 21.55% RT-21.796) are the major compounds. The findings of this study show that P. wightianus extracts may be used as an anti-infective agent in folklore medicine. PMID:24883301

Chemical regulation of body feather microbiota in a wild bird.

PubMed

Jacob, Staffan; Sallé, Louis; Zinger, Lucie; Chaine, Alexis S; Ducamp, Christine; Boutault, Léa; Russell, Andrew F; Heeb, Philipp

2018-04-01

The microbiota has a broad range of impacts on host physiology and behaviour, pointing out the need to improve our comprehension of the drivers of host-microbiota composition. Of particular interest is whether the microbiota is acquired passively, or whether and to what extent hosts themselves shape the acquisition and maintenance of their microbiota. In birds, the uropygial gland produces oily secretions used to coat feathers that have been suggested to act as an antimicrobial defence mechanism regulating body feather microbiota. However, our comprehension of this process is still limited. In this study, we for the first time coupled high-throughput sequencing of the microbiota of both body feathers and the direct environment (i.e., the nest) in great tits with chemical analyses of the composition of uropygial gland secretions to examine whether host chemicals have either specific effects on some bacteria or nonspecific broad-spectrum effects on the body feather microbiota. Using a network approach investigating the patterns of co-occurrence or co-exclusions between chemicals and bacteria within the body feather microbiota, we found no evidence for specific promicrobial or antimicrobial effects of uropygial gland chemicals. However, we found that one group of chemicals was negatively correlated to bacterial richness on body feathers, and a higher production of these chemicals was associated with a poorer body feather bacterial richness compared to the nest microbiota. Our study provides evidence that chemicals produced by the host might function as a nonspecific broad-spectrum antimicrobial defence mechanism limiting colonization and/or maintenance of bacteria on body feathers, providing new insight about the drivers of the host's microbiota composition in wild organisms. © 2018 John Wiley & Sons Ltd.

Underlying Mechanism of Antimicrobial Activity of Chitosan Microparticles and Implications for the Treatment of Infectious Diseases

PubMed Central

Jeon, Soo Jin; Oh, Manhwan; Yeo, Won-Sik; Galvão, Klibs N.; Jeong, Kwang Cheol

2014-01-01

The emergence of antibiotic resistant microorganisms is a great public health concern and has triggered an urgent need to develop alternative antibiotics. Chitosan microparticles (CM), derived from chitosan, have been shown to reduce E. coli O157:H7 shedding in a cattle model, indicating potential use as an alternative antimicrobial agent. However, the underlying mechanism of CM on reducing the shedding of this pathogen remains unclear. To understand the mode of action, we studied molecular mechanisms of antimicrobial activity of CM using in vitro and in vivo methods. We report that CM are an effective bactericidal agent with capability to disrupt cell membranes. Binding assays and genetic studies with an ompA mutant strain demonstrated that outer membrane protein OmpA of E. coli O157:H7 is critical for CM binding, and this binding activity is coupled with a bactericidal effect of CM. This activity was also demonstrated in an animal model using cows with uterine diseases. CM treatment effectively reduced shedding of intrauterine pathogenic E. coli (IUPEC) in the uterus compared to antibiotic treatment. Since Shiga-toxins encoded in the genome of bacteriophage is often overexpressed during antibiotic treatment, antibiotic therapy is generally not recommended because of high risk of hemolytic uremic syndrome. However, CM treatment did not induce bacteriophage or Shiga-toxins in E. coli O157:H7; suggesting that CM can be a potential candidate to treat infections caused by this pathogen. This work establishes an underlying mechanism whereby CM exert antimicrobial activity in vitro and in vivo, providing significant insight for the treatment of diseases caused by a broad spectrum of pathogens including antibiotic resistant microorganisms. PMID:24658463

Broad Spectrum Antimicrobial Activity of Forest-Derived Soil Actinomycete, Nocardia sp. PB-52

PubMed Central

Sharma, Priyanka; Kalita, Mohan C.; Thakur, Debajit

2016-01-01

A mesophilic actinomycete strain designated as PB-52 was isolated from soil samples of Pobitora Wildlife Sanctuary of Assam, India. Based on phenotypic and molecular characteristics, the strain was identified as Nocardia sp. which shares 99.7% sequence similarity with Nocardia niigatensis IFM 0330 (NR_112195). The strain is a Gram-positive filamentous bacterium with rugose spore surface which exhibited a wide range of antimicrobial activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA), Gram-negative bacteria, and yeasts. Optimization for the growth and antimicrobial activity of the strain PB-52 was carried out in batch culture under shaking condition. The optimum growth and antimicrobial potential of the strain were recorded in GLM medium at 28°C, initial pH 7.4 of the medium and incubation period of 8 days. Based on polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS) gene-targeted PCR amplification, the occurrence of both of these biosynthetic pathways was detected which might be involved in the production of antimicrobial compounds in PB-52. Extract of the fermented broth culture of PB-52 was prepared with organic solvent extraction method using ethyl acetate. The ethyl acetate extract of PB-52 (EA-PB-52) showed lowest minimum inhibitory concentration (MIC) against S. aureus MTCC 96 (0.975 μg/mL) whereas highest was recorded against Klebsiella pneumoniae ATCC 13883 (62.5 μg/mL). Scanning electron microscopy (SEM) revealed that treatment of the test microorganisms with EA-PB-52 destroyed the targeted cells with prominent loss of cell shape and integrity. In order to determine the constituents responsible for its antimicrobial activity, EA-PB-52 was subjected to chemical analysis using gas chromatography-mass spectrometry (GC-MS). GC-MS analysis showed the presence of twelve different chemical constituents in the extract, some of which are reported to possess diverse biological activity. These results confirmed that the presence of bioactive constituents in EA-PB-52 could be a promising source for the development of potent antimicrobial agents effective against wide range of microbial pathogens including MRSA. PMID:27047463

Highly potent silver-organoalkoxysilane antimicrobial porous nanomembrane

NASA Astrophysics Data System (ADS)

Umar, Sirajo; Liu, Yuanfeng; Wu, Yiguang; Li, Guangtao; Ding, Jiabo; Xiong, Runsong; Chen, Jinchun

2013-04-01

We used a simple electrospinning technique to fabricate a highly potent silver-organoalkoxysilane antimicrobial composite from AgNO3-polyvinylpyrrolidone (PVP)/3-aminopropyltrimethoxysilane (APTMS)/tetraethoxysilane (TEOS) solution. Spectroscopic and microscopic analyses of the composite showed that the fibers contain an organoalkoxysilane `skeleton,' 0.18 molecules/nm2 surface amino groups, and highly dispersed and uniformly distributed silver nanoparticles (5 nm in size). Incorporation of organoalkoxysilanes is highly beneficial to the antimicrobial mat as (1) amino groups of APTMS are adhesive and biocidal to microorganisms, (2) polycondensation of APTMS and TEOS increases the membrane's surface area by forming silicon bonds that stabilize fibers and form a composite mat with membranous structure and high porosity, and (3) the organoalkoxysilanes are also instrumental to the synthesis of the very small-sized and highly dispersed silver metal particles in the fiber mat. Antimicrobial property of the composite was evaluated by disk diffusion, minimum inhibition concentration (MIC), kinetic, and extended use assays on bacteria (Escherichia coli, Bacillus anthracis, Staphylococcus aureus, and Brucella suis), a fungus (Aspergillus niger), and the Newcastle disease virus. The membrane shows quick and sustained broad-spectrum antimicrobial activity. Only 0.3 mg of fibers is required to achieve MIC against all the test organisms. Bacteria are inhibited within 30 min of contact, and the fibers can be used repeatedly. The composite is silver efficient and environment friendly, and its membranous structure is suitable for many practical applications as in air filters, antimicrobial linen, coatings, bioadhesives, and biofilms.

Antimicrobial peptides of the genus Bacillus: a new era for antibiotics.

PubMed

Sumi, Chandra Datta; Yang, Byung Wook; Yeo, In-Cheol; Hahm, Young Tae

2015-02-01

The rapid onset of resistance reduces the efficacy of most conventional antimicrobial drugs and is a general cause of concern for human well-being. Thus, there is great demand for a continuous supply of novel antibiotics to combat this problem. Bacteria-derived antimicrobial peptides (AMPs) have long been used as food preservatives; moreover, prior to the development of conventional antibiotics, these AMPs served as an efficient source of antibiotics. Recently, peptides produced by members of the genus Bacillus were shown to have a broad spectrum of antimicrobial activity against pathogenic microbes. Bacillus-derived AMPs can be synthesized both ribosomally and nonribosomally and can be classified according to peptide biosynthesis, structure, and molecular weight. The precise mechanism of action of these AMPs is not yet clear; however, one proposed mechanism is that these AMPs kill bacteria by forming channels in and (or) disrupting the bacterial cell wall. Bacillus-derived AMPs have potential in the pharmaceutical industry, as well as the food and agricultural sectors. Here, we focus on Bacillus-derived AMPs as a novel alternative approach to antibacterial drug development. We also provide an overview of the biosynthesis, mechanisms of action, applications, and effectiveness of different AMPs produced by members of the Bacillus genus, including several recently identified novel AMPs.

Discovery of Phylloseptins that Defense against Gram-Positive Bacteria and Inhibit the Proliferation of the Non-Small Cell Lung Cancer Cell Line, from the Skin Secretions of Phyllomedusa Frogs.

PubMed

Liu, Jia; Wu, Qing; Li, Lei; Xi, Xinping; Wu, Di; Zhou, Mei; Chen, Tianbao; Shaw, Chris; Wang, Lei

2017-08-29

The growing occurrence of bacterial resistance to conventional antibiotics has called for the development of new classes of antimicrobial agents. Antimicrobial peptides (AMPs) with broad antimicrobial spectrum derived from frog skin secretions have been demonstrated to be promising candidates for new antibiotic development. A proven rich source of these compounds are the skin secretions of the frogs in the Phyllomedusa genus. In this study, two novel phylloseptin peptides-phylloseptin-PTa and phylloseptin-PHa-were isolated from the skin secretions of the South American frogs, Phyllomedusa tarsius ( P. tarsius ) and Phyllomedusa hypochondrialis ( P. hypochondrialis ) through parallel transcriptomic and peptidomic studies. Replicates obtained by chemical synthesis were structurally analysed and shown to adopt an α-helix configuration in an amphiphilic environment. Both peptides demonstrated antimicrobial activities against planktonic Gram-positive bacteria strains, including Staphylococcus aureus , Enterococcus faecalis and methicillin-resistant Staphylococcus aureus , biofilms, as well as cytostatic effects on the non-small cell lung cancer cell line, NCI-H157, with relatively low haemolysis on horse erythrocytes and low cytotoxicity on the human microvascular endothelial cell line, HMEC-1. The discovery of phylloseptin peptides may further inspire the development of new types of antibiotics.

Implication of PKS type I gene and chromatographic strategy for the biodiscovery of antimicrobial polyketide metabolites from endosymbiotic Nocardiopsis prasina CLA68

NASA Astrophysics Data System (ADS)

Rao, H. C. Yashavantha; Rakshith, Devaraju; Gurudatt, D. M.; Satish, Sreedharamurthy

2016-06-01

Advanced approach in probing for polyketide antimicrobials requires novel genomics and chromatographic strategies. An endophytic strain CLA68 was isolated from the root of Combretum latifolium Blume (Combretaceae) collected from the Western Ghats of Southern India. Strain CLA68 was then identified as Nocardiopsis prasina by its characteristic culture morphology and analysis of 16S rRNA gene sequence. Biosynthetic polyketide synthase genes were investigated using two pairs of degenerate primers. Ethyl acetate extract of CLA68 exhibited broad spectrum activity against a panel of test human pathogens. PKS type-I gene detection and chromatographic strategy yielded a robust polyketide antimicrobial compound which identified as nocapyrone E. Minimum inhibitory concentration of the purified compound against MRSA and other human pathogens ranged between 25 and 100 μg/ml. The present work highlights the utility of N. prasina CLA68 as potential source for antimicrobial polyketide nocapyrone E which could help to combat multidrug-resistant pathogens. This study demonstrates feasibility of PKS type-I gene-based molecular approach and chemical investigation by chromatographic approach is the best method for prediction and rapid discovery of novel polyketides from endosymbiotic actinomycetes. The sequence data of this endosymbiotic actinomycete is deposited in GenBank under the accession no. KP269077.

Antimicrobial peptides with selective antitumor mechanisms: prospect for anticancer applications.

PubMed

Deslouches, Berthony; Di, Y Peter

2017-07-11

In the last several decades, there have been significant advances in anticancer therapy. However, the development of resistance to cancer drugs and the lack of specificity related to actively dividing cells leading to toxic side effects have undermined these achievements. As a result, there is considerable interest in alternative drugs with novel antitumor mechanisms. In addition to the recent approach using immunotherapy, an effective but much cheaper therapeutic option of pharmaceutical drugs would still provide the best choice for cancer patients as the first line treatment. Ribosomally synthesized cationic antimicrobial peptides (AMPs) or host defense peptides (HDP) display broad-spectrum activity against bacteria based on electrostatic interactions with negatively charged lipids on the bacterial surface. Because of increased proportions of phosphatidylserine (negatively charged) on the surface of cancer cells compared to normal cells, cationic amphipathic peptides could be an effective source of anticancer agents that are both selective and refractory to current resistance mechanisms. We reviewed herein the prospect for AMP application to cancer treatment, with a focus on modes of action of cationic AMPs.

Bacillus subtilis HJ18-4 from traditional fermented soybean food inhibits Bacillus cereus growth and toxin-related genes.

PubMed

Eom, Jeong Seon; Lee, Sun Young; Choi, Hye Sun

2014-11-01

Bacillus subtilis HJ18-4 isolated from buckwheat sokseongjang, a traditional Korean fermented soybean food, exhibits broad-spectrum antimicrobial activity against foodborne pathogens, including Bacillus cereus. In this study, we investigated the antibacterial efficacy and regulation of toxin gene expression in B. cereus by B. subtilis HJ18-4. Expression of B. cereus toxin-related genes (groEL, nheA, nheC, and entFM) was downregulated by B. subtilis HJ18-4, which also exhibited strong antibacterial activity against B. cereus. We also found that water extracts of soy product fermented with B. subtilis HJ18-4 significantly inhibited the growth of B. cereus and toxin expression. These results indicate that B. subtilis HJ18-4 could be used as an antimicrobial agent to control B. cereus in the fermented soybean food industry. Our findings also provide an opportunity to develop an efficient biological control agent against B. cereus. © 2014 The Authors. Journal of Food Science published by Wiley Periodicals, Inc. on behalf of Institute of Food Technologists®

Antimicrobial peptides with selective antitumor mechanisms: prospect for anticancer applications

PubMed Central

Deslouches, Berthony; Di, Y. Peter

2017-01-01

In the last several decades, there have been significant advances in anticancer therapy. However, the development of resistance to cancer drugs and the lack of specificity related to actively dividing cells leading to toxic side effects have undermined these achievements. As a result, there is considerable interest in alternative drugs with novel antitumor mechanisms. In addition to the recent approach using immunotherapy, an effective but much cheaper therapeutic option of pharmaceutical drugs would still provide the best choice for cancer patients as the first line treatment. Ribosomally synthesized cationic antimicrobial peptides (AMPs) or host defense peptides (HDP) display broad-spectrum activity against bacteria based on electrostatic interactions with negatively charged lipids on the bacterial surface. Because of increased proportions of phosphatidylserine (negatively charged) on the surface of cancer cells compared to normal cells, cationic amphipathic peptides could be an effective source of anticancer agents that are both selective and refractory to current resistance mechanisms. We reviewed herein the prospect for AMP application to cancer treatment, with a focus on modes of action of cationic AMPs. PMID:28422728

Antimicrobial activity of commercial Olea europaea (olive) leaf extract.

PubMed

Sudjana, Aurelia N; D'Orazio, Carla; Ryan, Vanessa; Rasool, Nooshin; Ng, Justin; Islam, Nabilah; Riley, Thomas V; Hammer, Katherine A

2009-05-01

The aim of this research was to investigate the activity of a commercial extract derived from the leaves of Olea europaea (olive) against a wide range of microorganisms (n=122). Using agar dilution and broth microdilution techniques, olive leaf extract was found to be most active against Campylobacter jejuni, Helicobacter pylori and Staphylococcus aureus [including meticillin-resistant S. aureus (MRSA)], with minimum inhibitory concentrations (MICs) as low as 0.31-0.78% (v/v). In contrast, the extract showed little activity against all other test organisms (n=79), with MICs for most ranging from 6.25% to 50% (v/v). In conclusion, olive leaf extract was not broad-spectrum in action, showing appreciable activity only against H. pylori, C. jejuni, S. aureus and MRSA. Given this specific activity, olive leaf extract may have a role in regulating the composition of the gastric flora by selectively reducing levels of H. pylori and C. jejuni.

Large scale ab initio modeling of structurally uncharacterized antimicrobial peptides reveals known and novel folds.

PubMed

Kozic, Mara; Fox, Stephen J; Thomas, Jens M; Verma, Chandra S; Rigden, Daniel J

2018-05-01

Antimicrobial resistance within a wide range of infectious agents is a severe and growing public health threat. Antimicrobial peptides (AMPs) are among the leading alternatives to current antibiotics, exhibiting broad spectrum activity. Their activity is determined by numerous properties such as cationic charge, amphipathicity, size, and amino acid composition. Currently, only around 10% of known AMP sequences have experimentally solved structures. To improve our understanding of the AMP structural universe we have carried out large scale ab initio 3D modeling of structurally uncharacterized AMPs that revealed similarities between predicted folds of the modeled sequences and structures of characterized AMPs. Two of the peptides whose models matched known folds are Lebocin Peptide 1A (LP1A) and Odorranain M, predicted to form β-hairpins but, interestingly, to lack the intramolecular disulfide bonds, cation-π or aromatic interactions that generally stabilize such AMP structures. Other examples include Ponericin Q42, Latarcin 4a, Kassinatuerin 1, Ceratotoxin D, and CPF-B1 peptide, which have α-helical folds, as well as mixed αβ folds of human Histatin 2 peptide and Garvicin A which are, to the best of our knowledge, the first linear αββ fold AMPs lacking intramolecular disulfide bonds. In addition to fold matches to experimentally derived structures, unique folds were also obtained, namely for Microcin M and Ipomicin. These results help in understanding the range of protein scaffolds that naturally bear antimicrobial activity and may facilitate protein design efforts towards better AMPs. © 2018 The Authors Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.

A novel chimeric peptide with antimicrobial activity.

PubMed

Alaybeyoglu, Begum; Akbulut, Berna Sariyar; Ozkirimli, Elif

2015-04-01

Beta-lactamase-mediated bacterial drug resistance exacerbates the prognosis of infectious diseases, which are sometimes treated with co-administration of beta-lactam type antibiotics and beta-lactamase inhibitors. Antimicrobial peptides are promising broad-spectrum alternatives to conventional antibiotics in this era of evolving bacterial resistance. Peptides based on the Ala46-Tyr51 beta-hairpin loop of beta-lactamase inhibitory protein (BLIP) have been previously shown to inhibit beta-lactamase. Here, our goal was to modify this peptide for improved beta-lactamase inhibition and cellular uptake. Motivated by the cell-penetrating pVEC sequence, which includes a hydrophobic stretch at its N-terminus, our approach involved the addition of LLIIL residues to the inhibitory peptide N-terminus to facilitate uptake. Activity measurements of the peptide based on the 45-53 loop of BLIP for enhanced inhibition verified that the peptide was a competitive beta-lactamase inhibitor with a K(i) value of 58 μM. Incubation of beta-lactam-resistant cells with peptide decreased the number of viable cells, while it had no effect on beta-lactamase-free cells, indicating that this peptide had antimicrobial activity via beta-lactamase inhibition. To elucidate the molecular mechanism by which this peptide moves across the membrane, steered molecular dynamics simulations were carried out. We propose that addition of hydrophobic residues to the N-terminus of the peptide affords a promising strategy in the design of novel antimicrobial peptides not only against beta-lactamase but also for other intracellular targets. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

Activity Augmentation of Amphioxus Peptidoglycan Recognition Protein BbtPGRP3 via Fusion with a Chitin Binding Domain

PubMed Central

Wang, Wen-Jie; Cheng, Wang; Luo, Ming; Yan, Qingyu; Yu, Hong-Mei; Li, Qiong; Cao, Dong-Dong; Huang, Shengfeng; Xu, Anlong; Mariuzza, Roy A.; Chen, Yuxing; Zhou, Cong-Zhao

2015-01-01

Peptidoglycan recognition proteins (PGRPs), which have been identified in most animals, are pattern recognition molecules that involve antimicrobial defense. Resulting from extraordinary expansion of innate immune genes, the amphioxus encodes many PGRPs of diverse functions. For instance, three isoforms of PGRP encoded by Branchiostoma belcheri tsingtauense, termed BbtPGRP1~3, are fused with a chitin binding domain (CBD) at the N-terminus. Here we report the 2.7 Å crystal structure of BbtPGRP3, revealing an overall structure of an N-terminal hevein-like CBD followed by a catalytic PGRP domain. Activity assays combined with site-directed mutagenesis indicated that the individual PGRP domain exhibits amidase activity towards both DAP-type and Lys-type peptidoglycans (PGNs), the former of which is favored. The N-terminal CBD not only has the chitin-binding activity, but also enables BbtPGRP3 to gain a five-fold increase of amidase activity towards the Lys-type PGNs, leading to a significantly broadened substrate spectrum. Together, we propose that modular evolution via domain shuffling combined with gene horizontal transfer makes BbtPGRP1~3 novel PGRPs of augmented catalytic activity and broad recognition spectrum. PMID:26479246

Blue light enhances the antimicrobial activity of honey against Pseudomonas aeruginosa

NASA Astrophysics Data System (ADS)

Orlandi, Viviana Teresa; Bolognese, Fabrizio; Barbieri, Paola

2018-02-01

Pseudomonas aeruginosa may be isolated from skin wounds of burn patients, bedsore and diabetic ulcers. The healing of wounds is often impaired by the intrinsic antibiotic resistance, the tolerance to many antimicrobials and the ability to form biofilm of this opportunistic pathogen. Finding new topical treatments to combine with antibiotics is thus essential. Among natural products, the antimicrobial properties of honeys have been known for millennia. In this study honey and visible light have been combined to control the growth of P. aeruginosa PAO1. The irradiation by a broad spectrum light source of bacteria inoculated onto 2 % w/v fir and forest honeydew (HD) honeys caused a killing effect that the honeys alone or the light alone did not show. This antimicrobial activity was light energy-dose and honey-concentration dependent. Among the tested honeys, the fir and forest HD honeys were the most efficient ones. In particular, the irradiation by blue LED (λmax = 466 nm) yielded good rates of killing, that were significantly higher in comparison to irradiation alone and honey alone. Interestingly, a similar effect was obtained by plating bacteria on blue LED pre-irradiated HD honeys. The combined use of honey and blue light was also successful in inhibiting the biofilm formation of P. aeruginosa. The blue LED irradiation of PAO1 administered with 10 % w/v forest HD honey significantly enhanced the inhibition of biofilm formation in comparison to dark incubated honey.

Antifungal Activity of Eucalyptus Oil against Rice Blast Fungi and the Possible Mechanism of Gene Expression Pattern.

PubMed

Zhou, Li-Jun; Li, Fu-Rong; Huang, Li-Jie; Yang, Zhi-Rong; Yuan, Shu; Bai, Lin-Han

2016-05-12

Eucalyptus oil possesses a wide spectrum of biological activity, including anti-microbial, fungicidal, herbicidal, acaricidal and nematicidal properties. We studied anti-fungal activities of the leaf oil extracted from Eucalyptus. grandis × E. urophylla. Eleven plant pathogenic fungi were tested based on the mycelium growth rates with negative control. The results showed that Eucalyptus oil has broad-spectrum inhibitory effects toward these fungi. Remarkable morphological and structural alterations of hypha have been observed for Magnaporthe grisea after the treatment. The mRNA genome array of M. grisea was used to detect genes that were differentially expressed in the test strains treated by the Eucalyptus oil than the normal strains. The results showed 1919 genes were significantly affected, among which 1109 were down-regulated and 810 were up-regulated (p < 0.05, absolute fold change >2). According to gene ontology annotation analysis, these differentially expressed genes may cause abnormal structures and physiological function disorders, which may reduce the fungus growth. These results show the oil has potential for use in the biological control of plant disease as a green biopesticide.

Characterization of Antibacterial Activities of Eastern Subterranean Termite, Reticulitermes flavipes, against Human Pathogens

PubMed Central

Zeng, Yuan; Hu, Xing Ping

2016-01-01

The emergence and dissemination of multidrug resistant bacterial pathogens necessitate research to find new antimicrobials against these organisms. We investigated antimicrobial production by eastern subterranean termites, Reticulitermes flavipes, against a panel of bacteria including three multidrug resistant (MDR) and four non-MDR human pathogens. We determined that the crude extract of naïve termites had a broad-spectrum activity against the non-MDR bacteria but it was ineffective against the three MDR pathogens Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), and Acinetobacter baumannii. Heat or trypsin treatment resulted in a complete loss of activity suggesting that antibacterial activity was proteinaceous in nature. The antimicrobial activity changed dramatically when the termites were fed with either heat-killed P. aeruginosa or MRSA. Heat-killed P. aeruginosa induced activity against P. aeruginosa and MRSA while maintaining or slightly increasing activity against non-MDR bacteria. Heat-killed MRSA induced activity specifically against MRSA, altered the activity against two other Gram-positive bacteria, and inhibited activity against three Gram-negative bacteria. Neither the naïve termites nor the termites challenged with heat-killed pathogens produced antibacterial activity against A. baumannii. Further investigation demonstrated that hemolymph, not the hindgut, was the primary source of antibiotic activity. This suggests that the termite produces these antibacterial activities and not the hindgut microbiota. Two-dimensional gel electrophoretic analyses of 493 hemolymph protein spots indicated that a total of 38 and 65 proteins were differentially expressed at least 2.5-fold upon being fed with P. aeruginosa and MRSA, respectively. Our results provide the first evidence of constitutive and inducible activities produced by R. flavipes against human bacterial pathogens. PMID:27611223

The Biological Activities of Sesterterpenoid-Type Ophiobolins.

PubMed

Tian, Wei; Deng, Zixin; Hong, Kui

2017-07-18

Ophiobolins (Ophs) are a group of tricarbocyclic sesterterpenoids whose structures contain a tricyclic 5-8-5 carbotricyclic skeleton. Thus far, 49 natural Ophs have been reported and assigned into A-W subgroups in order of discovery. While these sesterterpenoids were first characterized as highly effective phytotoxins, later investigations demonstrated that they display a broad spectrum of biological and pharmacological characteristics such as phytotoxic, antimicrobial, nematocidal, cytotoxic, anti-influenza and inflammation-promoting activities. These bioactive molecules are promising drug candidates due to the developments of their anti-proliferative activities against a vast number of cancer cell lines, multidrug resistance (MDR) cells and cancer stem cells (CSCs). Despite numerous studies on the biological functions of Ophs, their pharmacological mechanism still requires further research. This review summarizes the chemical structures, sources, and biological activities of the oph family and discusses its mechanisms and structure-activity relationship to lay the foundation for the future developments and applications of these promising molecules.

Rationally designed dual functional block copolymers for bottlebrush-like coatings: In vitro and in vivo antimicrobial, antibiofilm, and antifouling properties.

PubMed

Gao, Qiang; Yu, Meng; Su, Yajuan; Xie, Meihua; Zhao, Xin; Li, Peng; Ma, Peter X

2017-03-15

Numerous antimicrobial coatings have been developed for biomedical devices/implants, but few can simultaneously fulfill the requirements for antimicrobial and antifouling ability and biocompatibility. In this study, to develop an antimicrobial and antibiofilm surface coating, diblock amphiphilic molecules with antimicrobial and antifouling segments in a single chain were rationally designed and synthesized. Cationic antimicrobial polypeptides (AMP) were first synthesized by N-carboxyanhydride ring-opening polymerization (NCA-ROP). Heterofunctionalized poly(ethylene glycol) with different lengths (methacrylate-PEG n -tosyl, n=10/45/90) was synthesized and site-specifically conjugated with polypeptides to form diblock amphiphiles. Along with increased PEG chain length, hemolytic activity was considerably improved, and broad-spectrum antimicrobial activity is retained. Three MA-PEG n -b-AMP copolymers were further grafted onto the surface of silicone rubber (a commonly used catheter material) via plasma/UV-induced surface polymerizations to form a bottlebrush-like coating with excellent antimicrobial activity against several pathogenic bacteria (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus), and effectively prevent biofilm formation. This bottlebrush coating also greatly reduced protein adsorption and platelet adhesion, indicating its excellent antifouling ability. An in vitro cytotoxicity study also demonstrated that this coating is biocompatible with mammalian cells. After subcutaneous implantation of the materials in rats, we demonstrated that the g-PEG 45 -b-AMP bottlebrush coating exhibits significant anti-infective activity in vivo. Thus, this facilely synthesized PEGylated AMP bottlebrush coating is a feasible method to prevent biomedical devices-associated infections. Current antimicrobial coatings are often associated with concerns such as antibiotic resistance, environmental pollution, short-time antimicrobial activity, biofouling, poor blood compatibility and cytotoxicity, etc. To overcome these drawbacks, a robust PEGylated cationic amphiphilic peptides-based bottlebrush-like surface coating is demonstrated here, which fulfil the requirements of antimicrobial and antifouling as well as biocompatibility in the meantime. Briefly, the rational designed g-PEG n -b-AMP block copolymers (n=10/45/90) were synthesized and grafted on silicone surface. This bottlebrush-like coating efficiently kill the contacted bacteria and prevent the biofilm formation, greatly reduced protein and platelet adhesion. It also exhibits excellent blood compatibility and low cytotoxicity in vitro. In particular, g-PEG 45 -b-AMP coating exhibits significant anti-infection effect in vivo. This coating offering an effective strategy for combating biomedical devices-associated infections. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

cDNA cloning and characterization of the antibacterial peptide cecropin 1 from the diamondback moth, Plutella xylostella L.

PubMed

Jin, Fengliang; Sun, Qiang; Xu, Xiaoxia; Li, Linmiao; Gao, Gang; Xu, Yingjie; Yu, Xiaoqiang; Ren, Shunxiang

2012-10-01

Cecropins are linear cationic antibacterial peptides that have potent activities against microorganisms. In the present study, a 480bp full-length cDNA encoding diamondback moth (Plutella xylostella) cecropin 1 (designated as Px-cec1) was obtained using RT-PCR. A Northern blot analysis showed that the Px-cec1 transcript was predominantly expressed in fat bodies, hemocytes, midgut and epidermis with the highest expression level in fat bodies. The expression of Px-cec1 mRNA in fat bodies was significantly increased 24h after microbial challenge, with the highest induced expression by Staphylococcus aureus. A circular dichroism (CD) analysis revealed that the recombinant Px-cec1 mainly contained α-helixes. Antimicrobial assays demonstrated that recombinant Px-cec1 exhibited a broad spectrum of anti-microbial properties against fungi, Gram-positive and Gram-negative bacteria, but it did not exhibit hemolytic activity against human erythrocytes. Furthermore, Px-cec1 caused significant morphological alterations of S. aureus, as shown by scanning electron microscopy and transmission electron microscopy. These results demonstrated that Px-cec1 exerts its antibacterial activity by acting on the cell membrane to disrupt bacterial cell structures. Copyright © 2012 Elsevier Inc. All rights reserved.

Antimicrobial potential of Dialium guineense (Wild.) stem bark on some clinical isolates in Nigeria

PubMed Central

Olajubu, FA; Akpan, I; Ojo, DA; Oluwalana, SA

2012-01-01

Context: The persistent increase in the number of antibiotic-resistant strains of microorganisms has led to the development of more potent but also more expensive antibiotics. In most developing countries of the world these antibiotics are not readily affordable, thus making compliance difficult. This calls for research into alternative sources of antimicrobials. Dialium guineense is a shrub of the family Leguminosae. Its stem bark is used for the treatment of cough, toothache, and bronchitis. Aims: Despite the acclaimed efficacy of D guineense, there is no scientific evidence in its support. This work was carried out to assess the antimicrobial activity of D guineense in vitro against some clinical isolates. Materials and Methods: D guineense stem bark was collected and 50 gm of air-dried and powdered stem bark of the plant was soaked for 72 hours in 1 l of each of the six solvents used in this study. Each mixture was refluxed, agitated at 200 rpm for 1 hour, filtered using Whatman No. 1 filter paper and, finally, freeze dried. The extracts were then tested for antimicrobial activity using the agar diffusion method. Results: The highest percentage yield of 23.2% was obtained with ethanol. Phytochemical screening showed that D guineense contains anthraquinone, alkaloids, flavonoids, tannins, and saponins. The antimicrobial activity of the extracts revealed a broad spectrum of activity, with Salmonella typhi and Staphylococcus aureusa showing the greatest zones of inhibition (18.0 mm). Only Candida albicans among the fungi tested was inhibited by the extract. The greatest zone of inhibition among the fractions was 16.0 mm. D guineense exhibited bactericidal activity at the 7th and 9th hours against Streptococcus pneumoniae and S. aureus 25923 while the 10th hour against S. typhi and C. albicans. The greatest activity was noted against S pneumoniae, where there was reduced viable cell count after 6 hours of exposure. Conclusion: Stem bark extract of D guineense (Wild.) has the potential to be developed into an antimicrobial agent PMID:23776811

Studies on the production and purification of an antimicrobial compound and taxonomy of the producer isolated from the marine environment of the Sundarbans.

PubMed

Saha, M; Ghosh, D; Ghosh, D; Garai, D; Jaisankar, P; Sarkar, K K; Dutta, P K; Das, S; Jha, T; Mukherjee, J

2005-02-01

A microorganism isolated from the Sundarbans region of the Bay of Bengal, India, showed potent antimicrobial activity against gram-positive and gram-negative bacteria, molds, yeast and several multiple-drug-resistant (MDR) bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). The isolate grew in the presence of 20% (w/v) NaCl, antibiotic production being maximum with 5% (w/v) NaCl in the production medium. Natural seawater stimulated antibiotic biosynthesis. The absence of catabolite repression during the synthesis of the antimicrobial substance was demonstrated by the utilization of glucose by this isolate. The 16S rRNA gene of this aerobic, gram-positive, mycelium- and spore-forming microorganism was amplified, and molecular phylogenetic analysis of the DNA sequence showed less than 93% similarity with its closest relative, indicating differentiation at the genus level. The highly stable, active principle was purified by butyl acetate extraction and silica-gel chromatography and a single compound was found to posses the broad-spectrum activity. Molecular characterization showed that the active compound is a lipid. Bioreactor studies demonstrated that antibiotic production is strongly dependent on the scale of operation and there is a definite relation between the dissolved oxygen concentration, medium pH, glucose utilization, cell differentiation and antibiotic production. Maximum production in 30 h could be obtained by regulation of the medium pH in the alkaline range by a combination of controlled addition of NaOH, regulation of the air supply and changes in the reactor configuration. Considering all of the above evidences and based on comparison with the current literature, a novel antimicrobial appears to have been isolated.

The antimicrobial stewardship program in Gulf Cooperation Council (GCC) states: insights from a regional survey.

PubMed

Enani, Mushira A

2016-01-01

The purpose of the current study is to describe the prevalence and characteristics of antimicrobial stewardship programs (ASP) in Gulf Cooperation Council (GCC) states to explore opportunities and overcome barriers to effective ASP implementation. A cross-sectional questionnaire survey was used to evaluate the current status of ASP: major stewardship components, barriers of implementation and program impact in acute care hospitals of GCC states. Forty-seven healthcare professionals responded from four GCC states, the majority from Saudi Arabia (81%). Twenty-nine (62%) participating hospitals had ASP in place. Of these established programs, 35 (75%) reported lack of funding and personnel as major barriers to program implementation. The top three objectives cited for the hospital ASP were to reduce resistance (72.3%), improve clinical outcomes (70.2%) and reduce costs (44.7%). The reported impact of existing ASP was reduction of inappropriate prescribing (68%), reduction of broad spectrum antibiotic use (63.8%), reduction of healthcare-associated infections (61.7%), reduction of length of stay or mortality metrics (59.6%), reduction in direct antibiotic cost (57.4%) and reduction of reported antibiotic resistance (55.3%). Survey participants from GCC states who have implemented ASP report significant impacts in the reduction of broad spectrum antibiotic use, hospital-acquired infection, inappropriate prescribing and antimicrobial resistance. These findings suggest a promising opportunity to enhance existing ASP through sharing of best practices and support the development of regional guidelines across GCC states.

The antimicrobial stewardship program in Gulf Cooperation Council (GCC) states: insights from a regional survey

PubMed Central

2015-01-01

Objectives: The purpose of the current study is to describe the prevalence and characteristics of antimicrobial stewardship programs (ASP) in Gulf Cooperation Council (GCC) states to explore opportunities and overcome barriers to effective ASP implementation. Methods: A cross-sectional questionnaire survey was used to evaluate the current status of ASP: major stewardship components, barriers of implementation and program impact in acute care hospitals of GCC states. Results: Forty-seven healthcare professionals responded from four GCC states, the majority from Saudi Arabia (81%). Twenty-nine (62%) participating hospitals had ASP in place. Of these established programs, 35 (75%) reported lack of funding and personnel as major barriers to program implementation. The top three objectives cited for the hospital ASP were to reduce resistance (72.3%), improve clinical outcomes (70.2%) and reduce costs (44.7%). The reported impact of existing ASP was reduction of inappropriate prescribing (68%), reduction of broad spectrum antibiotic use (63.8%), reduction of healthcare-associated infections (61.7%), reduction of length of stay or mortality metrics (59.6%), reduction in direct antibiotic cost (57.4%) and reduction of reported antibiotic resistance (55.3%). Conclusion: Survey participants from GCC states who have implemented ASP report significant impacts in the reduction of broad spectrum antibiotic use, hospital-acquired infection, inappropriate prescribing and antimicrobial resistance. These findings suggest a promising opportunity to enhance existing ASP through sharing of best practices and support the development of regional guidelines across GCC states. PMID:28989448

Safety Concerns Surrounding Quinolone Use in Children

PubMed Central

Patel, Karisma; Goldman, Jennifer L.

2016-01-01

Fluoroquinolones are highly effective antibiotics with many desirable pharmacokinetic and pharmacodynamic properties including high bioavailability, large volume of distribution, and a broad spectrum of antimicrobial activity. Despite their attractive profile as anti-infective agents, their use in children is limited, primarily due to safety concerns. In this review we highlight the pharmacological properties of fluoroquinolones and describe their current use in pediatrics. In addition, we provide a comprehensive assessment of the safety data associated with fluoroquinolone use in children. Although permanent or destructive arthropathy remains a significant concern, currently available data demonstrate that arthralgia and arthropathy are relatively uncommon in children and resolve following cessation of fluoroquinolone exposure without resulting in long-term sequelae. The concern for safety and risk of adverse events associated with pediatric fluoroquinolone use is likely driving the limited prescribing of this drug class in pediatrics. However, in adults, fluoroquinolones are the most commonly prescribed broad-spectrum antibiotics, resulting in the development of drug-resistant bacteria that can be challenging to treat effectively. The consequence of misuse and overuse of fluoroquinolones leading to drug resistance is a greater, but frequently overlooked, safety concern that applies to both children and adults and one that should be considered at the point of prescribing. PMID:26865283

Sparing carbapenem usage.

PubMed

Wilson, A Peter R

2017-09-01

Carbapenem resistance in Gram-negative bacteria is increasing in many countries and use of carbapenems and antibiotics to which resistance is linked should be reduced to slow its emergence. There are no directly equivalent antibiotics and the alternatives are less well supported by clinical trials. The few new agents are expensive. To provide guidance on strategies to reduce carbapenem usage. A literature review was performed as described in the BSAC/HIS/BIA/IPS Joint Working Party on Multiresistant Gram-negative Infection Report. Older agents remain active against some of the pathogens, although expectations of broad-spectrum cover for empirical treatment have risen. Education, expert advice on treatment and antimicrobial stewardship can produce significant reductions in use. More agents may need to be introduced onto the antibiotic formulary of the hospital, despite the poor quality of scientific studies in some cases. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Use of rifaximin in gastrointestinal and liver diseases

PubMed Central

Shayto, Rani H; Abou Mrad, Rachel; Sharara, Ala I

2016-01-01

Rifaximin is a broad spectrum oral antibiotic with antimicrobial activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria. It is poorly absorbed and thus has a highly favorable safety profile. Rifaximin has been shown to be effective in the treatment of traveler’s diarrhea, functional bloating and irritable bowel syndrome, small bowel bacterial overgrowth and in the prevention of recurrent overt hepatic encephalopathy. In addition, there is emerging evidence for a possible beneficial effect of rifaximin in the treatment of uncomplicated diverticular disease and in the prevention of recurrent diverticulitis. The use of rifaximin is associated with a low incidence of development, or persistence of spontaneous bacterial mutants. Moreover, the development of important drug resistance among extra-intestinal flora during rifaximin therapy is unlikely because of minimal systemic absorption and limited cross-resistance of rifaximin with other antimicrobials. This review addresses the current and emerging role of rifaximin in the treatment of gastrointestinal and liver disorders. PMID:27547007

Caprylic and Polygalacturonic Acid Combinations for Eradication of Microbial Organisms Embedded in Biofilm

PubMed Central

Rosenblatt, Joel; Reitzel, Ruth A.; Vargas-Cruz, Nylev; Chaftari, Anne-Marie; Hachem, Ray; Raad, Issam

2017-01-01

There is a need for non-antibiotic, antimicrobial compositions with low toxicity capable of broad-spectrum eradication of pathogenic biofilms in food preparation and healthcare settings. In this study we demonstrated complete biofilm eradication within 60 min with synergistic combinations of caprylic and polygalacturonic (PG) acids in an in vitro biofilm eradication model against representative hospital and foodborne infectious pathogen biofilms (methicillin-resistant Staphylococcus aureus, multidrug-resistant Pseudomonas aeruginosa, Candida albicans, Escherichia coli, and Salmonella enteritidis). Antimicrobial synergy against biofilms was demonstrated by quantifying viable organisms remaining in biofilms exposed to caprylic acid alone, PG acid alone, or combinations of the two. The combinations also synergistically inhibited growth of planktonic organisms. Toxicity of the combination was assessed in vitro on L929 fibroblasts incubated with extracts of caprylic and PG acid combinations using the Alamar Blue metabolic activity assay and the Trypan Blue exclusion cell viability assay. The extracts did not produce cytotoxic responses relative to untreated control fibroblasts. PMID:29093703

An environmentally benign antimicrobial nanoparticle based on a silver-infused lignin core.

PubMed

Richter, Alexander P; Brown, Joseph S; Bharti, Bhuvnesh; Wang, Amy; Gangwal, Sumit; Houck, Keith; Cohen Hubal, Elaine A; Paunov, Vesselin N; Stoyanov, Simeon D; Velev, Orlin D

2015-09-01

Silver nanoparticles have antibacterial properties, but their use has been a cause for concern because they persist in the environment. Here, we show that lignin nanoparticles infused with silver ions and coated with a cationic polyelectrolyte layer form a biodegradable and green alternative to silver nanoparticles. The polyelectrolyte layer promotes the adhesion of the particles to bacterial cell membranes and, together with silver ions, can kill a broad spectrum of bacteria, including Escherichia coli, Pseudomonas aeruginosa and quaternary-amine-resistant Ralstonia sp. Ion depletion studies have shown that the bioactivity of these nanoparticles is time-limited because of the desorption of silver ions. High-throughput bioactivity screening did not reveal increased toxicity of the particles when compared to an equivalent mass of metallic silver nanoparticles or silver nitrate solution. Our results demonstrate that the application of green chemistry principles may allow the synthesis of nanoparticles with biodegradable cores that have higher antimicrobial activity and smaller environmental impact than metallic silver nanoparticles.

DNA-crosslinker cisplatin eradicates bacterial persister cells.

PubMed

Chowdhury, Nityananda; Wood, Thammajun L; Martínez-Vázquez, Mariano; García-Contreras, Rodolfo; Wood, Thomas K

2016-09-01

For all bacteria, nearly every antimicrobial fails since a subpopulation of the bacteria enter a dormant state known as persistence, in which the antimicrobials are rendered ineffective due to the lack of metabolism. This tolerance to antibiotics makes microbial infections the leading cause of death worldwide and makes treating chronic infections, including those of wounds problematic. Here, we show that the FDA-approved anti-cancer drug cisplatin [cis-diamminodichloroplatinum(II)], which mainly forms intra-strand DNA crosslinks, eradicates Escherichia coli K-12 persister cells through a growth-independent mechanism. Additionally, cisplatin is more effective at killing Pseudomonas aeruginosa persister cells than mitomycin C, which forms inter-strand DNA crosslinks, and cisplatin eradicates the persister cells of several pathogens including enterohemorrhagic E. coli, Staphylococcus aureus, and P. aeruginosa. Cisplatin was also highly effective against clinical isolates of S. aureus and P. aeruginosa. Therefore, cisplatin has broad spectrum activity against persister cells. Biotechnol. Bioeng. 2016;113: 1984-1992. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Gram-stain-based antimicrobial selection reduces cost and overuse compared with Japanese guidelines.

PubMed

Taniguchi, Tomohiro; Tsuha, Sanefumi; Shiiki, Soichi; Narita, Masashi

2015-10-26

The Gram stain has been used as an essential tool for antimicrobial stewardship in our hospital since the 1970s. The objective of this study was to clarify the difference in the targeted therapies selected based on the Gram stain and simulated empirical therapies based on the antimicrobial guidelines used in Japan. A referral-hospital-based prospective descriptive study was undertaken between May 2013 and April 2014 in Okinawa, Japan. All enrolled patients were adults who had been admitted to the Division of Infectious Diseases through the emergency room with suspected bacterial infection at one of three sites: respiratory system, urinary tract, or skin and soft tissues. The study outcomes were the types and effectiveness of the antibiotics initially selected, and their total costs. Two hundred eight patients were enrolled in the study. The median age was 80 years. A significantly narrower spectrum of antibiotics was selected based on the Gram stain than was selected based on the Japanese guidelines. The treatments based on the Gram stain and on the guidelines were estimated to be equally highly effective. The total cost of antimicrobials after Gram-stain testing was less than half the cost after the guidelines were followed. Compared with the Japanese guidelines, the Gram stain dramatically reduced the overuse of broad-spectrum antimicrobials without affecting the effectiveness of the treatment. Drug costs were reduced by half when the Gram stain was used. The Gram stain should be included in all antimicrobial stewardship programs.

Antimicrobial peptides from the skins of North American frogs.

PubMed

Conlon, J Michael; Kolodziejek, Jolanta; Nowotny, Norbert

2009-08-01

North America is home to anuran species belonging to the families Bufonidae, Eleutherodactylidae, Hylidae, Leiopelmatidae, Ranidae, and Scaphiopodidae but antimicrobial peptides have been identified only in skin secretions and/or skin extracts of frogs belonging to the Leiopelmatidae ("tailed frogs") and Ranidae ("true frogs"). Eight structurally-related cationic alpha-helical peptides with broad-spectrum antibacterial activity, termed ascaphins, have been isolated from specimens of Ascaphus truei (Leiopelmatidae) occupying a coastal range. Characterization of orthologous antimicrobial peptides from Ascaphus specimens occupying an inland range supports the proposal that this population should be regarded as a separate species A. montanus. Ascaphin-8 shows potential for development into a therapeutically valuable anti-infective agent. Peptides belonging to the brevinin-1, esculentin-1, esculentin-2, palustrin-1, palustrin-2, ranacyclin, ranatuerin-1, ranatuerin-2, and temporin families have been isolated from North American ranids. It is proposed that "ranalexins" represent brevinin-1 peptides that have undergone a four amino acid residue internal deletion. Current taxonomic recommendations divide North American frogs from the family Ranidae into two genera: Lithobates and Rana. Cladistic analysis based upon the amino acid sequences of the brevinin-1 peptides provides strong support for this assignment.

A case study of preservation of semi-solid preparations using the European Pharmacopoeia test: comparative efficacy of antimicrobial agents in zinc gelatin.

PubMed

Favet, J; Chappuis, M L; Doelker, E

2001-09-01

The present study was undertaken with the aim of finding an alternative preservative system to methyl parahydroxybenzoate in zinc gelatin, which was described in the monographs of the Swiss Pharmacopoeia (until Ph. Helv. 8) and in previous editions of the German Pharmacopoeia (until DAB 7). This antimicrobial agent has now been withdrawn in the DAB, because of its potential allergy risks. As for the USP and DAB-DDR zinc gelatin preparations, they have always been devoid of any preservative agent, probably relying on the mild antimicrobial activity of zinc. A literature survey did not reveal if such an aqueous preparation containing the water-insoluble zinc oxide shows efficacious antimicrobial activity by itself. Thus, a comparative evaluation of differently preserved zinc gelatin preparations was performed using a test for the efficacy of antimicrobial preservation that has been modified with regard to the European Pharmacopoeia (EP) test to take into account the solid state of the preparations and the bactericidal effect of the zinc. Three zinc gelatin preparations were checked, either: (i), without any agent; or (ii), with 0.1% methyl parahydroxybenzoate; or (iii), with 0.5% phenoxyethanol, a broad-spectrum antimicrobial agent almost devoid of allergy risks. The three preparations behave quite differently, in particular with respect to fungi. All three preparations passed the modified EP test as far as bacteria are concerned. Even zinc gelatin without preservative is very effective, not only because of the mild antimicrobial activity of zinc (the soluble fraction of zinc oxide in the liquid phase of zinc gelatin was determined to be 13 microg/ml), but most probably because of the low water activity of the preparation (measured as around 0.81), as shown by the absence of growth of a zinc-resistant strain of Pseudomonas aeruginosa. Zinc gelatin preserved with methyl parahydroxybenzoate has a weak, although satisfactory, activity against Staphylococcus aureus. Regarding fungi, gelatin without an antimicrobial agent and that preserved with methyl parahydroxybenzoate meet the requirements for efficacy against Candida albicans, but are only bacteriostatic against Aspergillus niger. As for zinc gelatin preserved with phenoxyethanol, it displays the best activity against C. albicans and, above all, appears to be the only formulation exhibiting fungicidal activity against A. niger. It is therefore recommended to preserve zinc gelatin with this antimicrobial agent, as recently adopted in Supplement 2000 of the Swiss Pharmacopoeia.

Insights into the anticancer properties of the first antimicrobial peptide from Archaea.

PubMed

Gaglione, Rosa; Pirone, Luciano; Farina, Biancamaria; Fusco, Salvatore; Smaldone, Giovanni; Aulitto, Martina; Dell'Olmo, Eliana; Roscetto, Emanuela; Del Gatto, Annarita; Fattorusso, Roberto; Notomista, Eugenio; Zaccaro, Laura; Arciello, Angela; Pedone, Emilia; Contursi, Patrizia

2017-09-01

The peptide VLL-28, identified in the sequence of an archaeal protein, the transcription factor Stf76 from Sulfolobus islandicus, was previously identified and characterized as an antimicrobial peptide, possessing a broad-spectrum antibacterial activity. Through a combined approach of NMR and Circular Dichroism spectroscopy, Dynamic Light Scattering, confocal microscopy and cell viability assays, the interaction of VLL-28 with the membranes of both parental and malignant cell lines has been characterized and peptide mechanism of action has been studied. It is here demonstrated that VLL-28 selectively exerts cytotoxic activity against murine and human tumor cells. By means of structural methodologies, VLL-28 interaction with the membranes has been proven and the binding residues have been identified. Confocal microscopy data show that VLL-28 is internalized only into tumor cells. Finally, it is shown that cell death is mainly caused by a time-dependent activation of apoptotic pathways. VLL-28, deriving from the archaeal kingdom, is here found to be endowed with selective cytotoxic activity towards both murine and human cancer cells and consequently can be classified as an ACP. VLL-28 represents the first ACP identified in an archaeal microorganism, exerting a trans-kingdom activity. Copyright © 2017 Elsevier B.V. All rights reserved.

Non-observance of guidelines for surgical antimicrobial prophylaxis and surgical-site infections.

PubMed

Lallemand, S; Thouverez, M; Bailly, P; Bertrand, X; Talon, D

2002-06-01

A prospective multicentre study was conducted to assess major aspects of surgical prophylaxis and to determine whether inappropriate antimicrobial prophylaxis was a factor associated (risk or protective factor) with surgical site infection (SSI). Surgical prophylaxis practices were assessed by analysing four variables: indication, antimicrobial agent, timing and duration. Univariate and multivariate analyses were carried out to identify predictors of SSI among patient-specific, operation-specific and antimicrobial prophylaxis-specific factors. The frequency of SSI was 2.7% (13 SSI in 474 observations). Total compliance of the prescription with guidelines was observed in 41.1% of cases (195 prescriptions). Of the 139 patients who received an inappropriate drug, 126 (90.6%) received a drug with a broader spectrum than the recommended drug. Prophylaxis was prolonged in 71 (87.7%) of the 81 patients who received prophylaxis for inappropriate lengths of time and 43 (61.4%) of the 70 patients who did not receive prophylaxis at the optimal moment were treated too late. Multivariate analysis clearly demonstrated that SSI was associated with multiple procedures (relative risk 8.5), short duration of prophylaxis (relative risk 12.7) and long-term therapy with antimicrobial agents during the previous year (relative risk 8.8). The ecological risk of the emergence of resistance associated with the frequent use of broad-spectrum antibiotics and prophylaxis for longer periods was not offset by individual benefit to the patients who received inappropriate prophylaxis.

Identification and Characterization of the First Cathelicidin from Sea Snakes with Potent Antimicrobial and Anti-inflammatory Activity and Special Mechanism*

PubMed Central

Wei, Lin; Gao, Jiuxiang; Zhang, Shumin; Wu, Sijin; Xie, Zeping; Ling, Guiying; Kuang, Yi-Qun; Yang, Yongliang; Yu, Haining; Wang, Yipeng

2015-01-01

Cathelicidins are a family of gene-encoded peptide effectors of innate immunity found exclusively in vertebrates. They play pivotal roles in host immune defense against microbial invasions. Dozens of cathelicidins have been identified from several vertebrate species. However, no cathelicidin from marine reptiles has been characterized previously. Here we report the identification and characterization of a novel cathelicidin (Hc-CATH) from the sea snake Hydrophis cyanocinctus. Hc-CATH is composed of 30 amino acids, and the sequence is KFFKRLLKSVRRAVKKFRKKPRLIGLSTLL. Circular dichroism spectroscopy and structure modeling analysis indicated that Hc-CATH mainly assumes an amphipathic α-helical conformation in bacterial membrane-mimetic solutions. It possesses potent broad-spectrum and rapid antimicrobial activity. Meanwhile, it is highly stable and shows low cytotoxicity toward mammalian cells. The microbial killing activity of Hc-CATH is executed through the disruption of cell membrane and lysis of bacterial cells. In addition, Hc-CATH exhibited potent anti-inflammatory activity by inhibiting the LPS-induced production of nitric oxide (NO) and pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. Hc-CATH directly binds with LPS to neutralize its toxicity, and it also binds to Toll-like receptor 4 (TLR4/MD2 complex), which therefore inhibits the binding of LPS to TLR4/MD2 complex and the subsequent activation of LPS-induced inflammatory response pathways. Taken together, our study demonstrates that Hc-CATH, the first cathelicidin from sea snake discovered to have both antimicrobial and anti-inflammatory activity, is a potent candidate for the development of peptide antibiotics. PMID:26013823

Three-day treatment with imipenem for unexplained fever during prolonged neutropaenia in haematology patients receiving fluoroquinolone and fluconazole prophylaxis: a prospective observational safety study.

PubMed

Slobbe, Lennert; Waal, Loes van der; Jongman, Lydia R; Lugtenburg, Pieternella J; Rijnders, Bart J A

2009-11-01

Guidelines advocate >7d of broad-spectrum antibiotics for unexplained fever (UF) during neutropaenia. However, effective antimicrobial prophylaxis reduces the incidence of gram-negative infections, which may allow shorter treatment. This study evaluates the safety of discontinuing empirical broad-spectrum antibiotics if no microbial source is documented after an initial work-up of 72 h. Prospective observational study at a tertiary-care haematology-unit in patients suffering from haematologic malignancies and treatment-induced prolonged neutropaenia of 10d. Oral fluoroquinolone and fluconazole prophylaxis was given from day 1. Fever was empirically treated with imipenem which was discontinued after 72 h if, following a standardised protocol, no infectious aetiology was documented. Duration of fever, antimicrobial therapy and overall mortality were registered. One hundred and sixty six patients were evaluated during 276 neutropaenic episodes. One hundred and thirty six patients (82.5%) experienced 1 febrile episode. A total of 317 febrile episodes were observed, of which 177 (56%) were diagnosed as UF. In 135 febrile episodes (43%), a probable/definite infectious origin was documented. Mean duration of fever in neutropaenic periods with 1 febrile episode was 5d, and mean time of treatment with imipenem was 4.7d. In patients without documented infection, mean time of imipenem treatment was only 3.7d. Overall mortality 30 d after neutrophil recovery was 3.6% (6/166); no patient died from untreated bacterial infection. Discontinuation of broad-spectrum antibiotics during neutropaenia in haematology patients on fluoroquinolone and fluconazole prophylaxis is safe, provided that no infectious aetiology is established after 72 h.

Identification of a broad-spectrum inhibitor of virus RNA synthesis: validation of a prototype virus-based approach

PubMed Central

Filone, Claire Marie; Hodges, Erin N.; Honeyman, Brian; Bushkin, G. Guy; Boyd, Karla; Platt, Andrew; Ni, Feng; Strom, Kyle; Hensley, Lisa; Snyder, John K.; Connor, John H.

2013-01-01

There are no approved therapeutics for the most deadly nonsegmented negative-strand (NNS) RNA viruses, including Ebola (EBOV). To identify new chemical scaffolds for development of broad-spectrum antivirals, we undertook a prototype-based lead identification screen. Using the prototype NNS virus, vesicular stomatitis virus (VSV), multiple inhibitory compounds were identified. Three compounds were investigated for broad-spectrum activity, and inhibited EBOV infection. The most potent, CMLDBU3402, was selected for further study. CMLDBU3402 did not show significant activity against segmented negative-strand RNA viruses suggesting proscribed broad-spectrum activity. Mechanistic analysis indicated that CMLDBU3402 blocked VSV viral RNA synthesis and inhibited EBOV RNA transcription, demonstrating a consistent mechanism of action against genetically distinct viruses. The identification of this chemical backbone as a broad-spectrum inhibitor of viral RNA synthesis offers significant potential for the development of new therapies for highly pathogenic viruses. PMID:23521799

Novel designed VmCT1 analogs with increased antimicrobial activity.

PubMed

Pedron, Cibele Nicolaski; Torres, Marcelo Der Torossian; Lima, Julia Aparecida da Silva; Silva, Pedro Ismael; Silva, Fernanda Dias; Oliveira, Vani Xavier

2017-01-27

Antimicrobial peptides are biologically active molecules produced by a wide range of organisms as an essential component of the innate immune response. They have recently attracted great interest, since they have antimicrobial activity against a broad spectrum of microorganisms. VmCT1 is a cationic peptide from the venom of Vaejovis mexicanus smithi scorpions, which presents antibacterial activity and tends to helical structures. Its analogs were synthesized, characterized and the conformational studies were performed by circular dichroism. The peptides were designed to verify if the single and double substitutions proposed at the hydrophilic and hydrophobic portions of the amphipathic structure would alter antimicrobial activity against Gram-negative and Gram-positive bacteria, yeast and filamentous fungus, besides the hemolytic activity in human erythrocytes. Total charge of the peptides were modified from +2 to +3 by the introduction of a Lysine residue in the hydrophilic face of the amphiphilic helical structure leading to enhanced antimicrobial activity. [K] 11 -VmCT1-NH 2 presented the lower MIC value against the microorganisms (from 0.39 to 6.25 μmol L -1 ), however it showed higher hemolytic activity. The other Lysine-substituted analogs presented also lower MIC values ranging from 0.39 to 25 μmol L -1 for the microorganisms assessed. The circular dichroism spectra analyses suggest that the Lysine-substituted analogs tend to adopt helical structures in trifluoroethanol solution and vesicles (f H : 0.43-1), however they were coiled in water. Alanine substitution by a Glutamic acid residue in the hydrophilic face promotes the increase of polar angle in [E] 4 -VmCT1-NH 2 analog, which was important to led lower hemolytic activity (MHC value = 25 μmol L -1 ). [W] 9 -VmCT1-NH 2 and [E] 4 [W] 9 -VmCT1-NH 2 were designed to favors hydrophobic interactions by the introduction of Tryptophan residue. [W] 9 -VmCT1-NH 2 presented MIC values lower or similar than the model molecule in the most of microorganisms tested. These results provided information about the structure-activity relationship and showed the influence of physicochemical parameters on antimicrobial and hemolytic activity. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Interscience Conference on Antimicrobial Agents and Chemotherapy--49th annual meeting. Part 2. 12-15 September 2009, San Francisco, CA, USA.

PubMed

Turner, Ben; Murch, Lisa

2009-11-01

The Interscience Conference on Antimicrobial Agents and Chemotherapy held in San Francisco included topics covering new therapeutic developments for the treatment of infectious diseases. This conference report highlights selected presentations on several antibiotics in development including a broad-spectrum penem beta-lactam antibiotic, a novel siderophore monobactam, as well as other novel antibiotics. Investigational drugs discussed include sulopenem and sulopenem etzadroxil (both Pfizer Inc), BAL-30072 (Basilea Pharmaceutica International Ltd), TP-120 and TP-787 (both Tetraphase Pharmaceuticals Inc), NAI-107 (New Anti Infectives Consortium/NexThera Biosciences) and ABI-200 (AdRem Biotech/US Department of Agriculture).

Resistance patterns of multidrug resistant Acinetobacter baumannii in an ICU of a tertiary care hospital, Malaysia

PubMed Central

Janahiraman, Sivakami; Aziz, Muhammad Nazri; Hoo, Fan Kee; P’ng, Hon Shen; Boo, Yang Liang; Ramachandran, Vasudevan; Shamsuddin, Ahmad Fuad

2015-01-01

Backgrounds & Objective: Antimicrobial resistance is a major health problem worldwide in hospitals. The main contributing factors are exposures to broad-spectrum antimicrobials and cross-infections. Understanding the extent and type of antimicrobial use in tertiary care hospitals will aid in developing national antimicrobial stewardship priorities. Methods: In this study, we have analyzed the antimicrobial agents’ usage for acquisition of multidrug resistant using retrospective, cross-sectional, single-centre study in a multidisciplinary ICU at tertiary care hospital. Results: Acinetobacter baumannii (ACB) was isolated in various specimens from 662 patients. From these, 136 patients who were diagnosed with Ventilator-associated pneumonia (VAP) caused by ACB were included into the study. In our study, MDR strain accounts for 51% of all VAP cases caused by ACB. The development of ACB VAP were 10.5 + 6.4 days for MDR strains compared to susceptible organism (7.8 + 4.5 days) and had significantly longer ICU stay. Conclusion: The study concludes that prudent use of antimicrobial agents is important to reduce acquisition of MDR ACB. PMID:26870101

Sensitization of Staphylococcus aureus to Methicillin and Other Antibiotics In Vitro and In Vivo in the Presence of HAMLET

PubMed Central

Marks, Laura R.; Clementi, Emily A.; Hakansson, Anders P.

2013-01-01

HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a protein-lipid complex from human milk with both tumoricidal and bactericidal activities. HAMLET exerts a rather specific bactericidal activity against some respiratory pathogens, with highest activity against Streptococcus pneumoniae, but lacks activity against most other bacterial pathogens, including Staphylococci. Still, ion transport associated with death in S. pneumoniae is also detected to a lower degree in insensitive organisms. In this study we demonstrate that HAMLET acts as an antimicrobial adjuvant that can increase the activity of a broad spectrum of antibiotics (methicillin, vancomycin, gentamicin and erythromycin) against multi-drug resistant Staphylococcus aureus, to a degree where they become sensitive to those same antibiotics, both in antimicrobial assays against planktonic and biofilm bacteria and in an in vivo model of nasopharyngeal colonization. We show that HAMLET exerts these effects specifically by dissipating the proton gradient and inducing a sodium-dependent calcium influx that partially depolarizes the plasma membrane, the same mechanism induced during pneumococcal death. These effects results in an increased cell associated binding and/or uptake of penicillin, gentamicin and vancomycin, especially in resistant stains. Finally, HAMLET inhibits the increased resistance of methicillin seen under antibiotic pressure and the bacteria do not become resistant to the adjuvant, which is a major advantageous feature of the molecule. These results highlight HAMLET as a novel antimicrobial adjuvant with the potential to increase the clinical usefulness of antibiotics against drug resistant strains of S. aureus. PMID:23650551

Monitoring of multiple bacteriocins through a developed dual extraction protocol and comparison of HPLC-DAD with turbidometry as their quantification system.

PubMed

Katharopoulos, Efstathios; Touloupi, Katerina; Touraki, Maria

2016-08-01

The present study describes the development of a simple and efficient screening system that allows identification and quantification of nine bacteriocins produced by Lactococcus lactis. Cell-free L. lactis extracts presented a broad spectrum of antibacterial activity, including Gram-negative bacteria, Gram-positive bacteria, and fungi. The characterization of their sensitivity to pH, and heat, showed that the extracts retained their antibacterial activity at extreme pH values and in a wide temperature range. The loss of antibacterial activity following treatment of the extracts with lipase or protease suggests a lipoproteinaceous nature of the produced antimicrobials. The extracts were subjected to a purification protocol that employs a two phase extraction using ammonium sulfate precipitation and organic solvent precipitation, followed by ion exchange chromatography, solid phase extraction and HPLC. In the nine fractions that presented antimicrobial activity, bacteriocins were quantified by the turbidometric method using a standard curve of nisin and by the HPLC method with nisin as the external standard, with both methods producing comparable results. Turbidometry appears to be unique in the qualitative determination of bacteriocins but the only method suitable to both separate and quantify the bacteriocins providing increased sensitivity, accuracy, and precision is HPLC. Copyright © 2016 Elsevier B.V. All rights reserved.

Antimicrobial Treatment of Polymeric Medical Devices by Silver Nanomaterials and Related Technology.

PubMed

Polívková, Markéta; Hubáček, Tomáš; Staszek, Marek; Švorčík, Václav; Siegel, Jakub

2017-02-15

Antimicrobial biocompatible polymers form a group of highly desirable materials in medicinal technology that exhibit interesting thermal and mechanical properties, and high chemical resistance. There are numerous types of polymers with antimicrobial activity or antimicrobial properties conferred through their proper modification. In this review, we focus on the second type of polymers, especially those whose antimicrobial activity is conferred by nanotechnology. Nanotechnology processing is a developing area that exploits the antibacterial effects of broad-scale compounds, both organic and inorganic, to form value-added medical devices. This work gives an overview of nanostructured antimicrobial agents, especially silver ones, used together with biocompatible polymers as effective antimicrobial composites in healthcare. The bactericidal properties of non-conventional antimicrobial agents are compared with those of conventional ones and the advantages and disadvantages are discussed.

Extracts containing CLPs of Bacillus amyloliquefaciens JN68 isolated from chicken intestines exert antimicrobial effects, particularly on methicillin-resistant Staphylococcus aureus and Listeria monocytogenes.

PubMed

Chen, Jen-Ni; Wei, Chyou-Wei; Liu, Hsiao-Chun; Chen, Shu-Ying; Chen, Chinshuh; Juang, Yu-Min; Lai, Chien-Chen; Yiang, Giou-Teng

2016-12-01

Bacillus amyloliquefaciens JN68, which has been discussed with regards to its antimicrobial activities, was successfully isolated from healthy chicken intestines in the present study. Using the spot-on-the-lawn antagonism method, the preliminary study indicated that a suspension culture of the B. amyloliquefaciens JN68 strain can inhibit the growth of Aspergillus niger and Penicillium pinophilum. Furthermore, the cyclic lipopeptides (CLPs) produced by the B. amyloliquefaciens JN68 strain were further purified through acid precipitation and Bond Elut®C18 chromatography, and their structures were identified using the liquid chromatography‑electrospray ionization‑mass spectrometry (MS)/MS method. Purified CLPs exerted broad spectrum antimicrobial activities on various pathogenic and foodborne bacteria and fungi, as determined using the agar well diffusion method. Listeria monocytogenes can induce listeriosis, which is associated with a high mortality rate. Methicillin‑resistant Staphylococcus aureus (MRSA) is a major pathogenic bacteria that causes nosocomial infections. Therefore, L. monocytogenes and MRSA are currently of great concern. The present study aimed to determine whether B. amyloliquefaciens JN68 extracts could inhibit L. monocytogenes and MRSA. The results indicated that extracts of B. amyloliquefaciens JN68 have CLP components, and can successfully inhibit the growth of L. monocytogenes and MRSA.

[Antimicrobial treatment in complicated intraabdominal infections--current situation].

PubMed

Vyhnánek, F

2009-04-01

Compared to other infections, intraabdominal infections include wide spectrum of infections of various severity, have different ethiology, which is frequently polymicrobial, show different microbiological results, which are difficult to interpret. The role of surgical intervention is essential. Intraabdominal infections are common causes of morbidity and mortality. Their prognosis is significantly improved with early and exact diagnosis, appropriate surgical or radiological intervention and timely effective antimicrobial therapy. Practitioners may choose between older or more modern antibiotics, between monotherapy or combination therapy, however, they should also consider clinical condition of the patient, the antibiotic's spectrum of activity, the treatment timing and its duration, the dose and dosing scheme of the particular antimicrobials. Furthermore, antimicrobial therapy should be used with caution, with the aim to prevent development of antimicrobial resistence. Inappropriate choice of antimicrobials in initial empiric therapy results in relapsing infections, surgical intervention and prolongation of hospitalization, and even death rates reflect adequate and timely empiric therapy.

Identification of agents effective against multiple toxins and viruses by host-oriented cell targeting.

PubMed

Zilbermintz, Leeor; Leonardi, William; Jeong, Sun-Young; Sjodt, Megan; McComb, Ryan; Ho, Chi-Lee C; Retterer, Cary; Gharaibeh, Dima; Zamani, Rouzbeh; Soloveva, Veronica; Bavari, Sina; Levitin, Anastasia; West, Joel; Bradley, Kenneth A; Clubb, Robert T; Cohen, Stanley N; Gupta, Vivek; Martchenko, Mikhail

2015-08-27

A longstanding and still-increasing threat to the effective treatment of infectious diseases is resistance to antimicrobial countermeasures. Potentially, the targeting of host proteins and pathways essential for the detrimental effects of pathogens offers an approach that may discover broad-spectrum anti-pathogen countermeasures and circumvent the effects of pathogen mutations leading to resistance. Here we report implementation of a strategy for discovering broad-spectrum host-oriented therapies against multiple pathogenic agents by multiplex screening of drugs for protection against the detrimental effects of multiple pathogens, identification of host cell pathways inhibited by the drug, and screening for effects of the agent on other pathogens exploiting the same pathway. We show that a clinically used antimalarial drug, Amodiaquine, discovered by this strategy, protects host cells against infection by multiple toxins and viruses by inhibiting host cathepsin B. Our results reveal the practicality of discovering broadly acting anti-pathogen countermeasures that target host proteins exploited by pathogens.

Triclosan resistance reversion by encapsulation in chitosan-coated-nanocapsule containing α-bisabolol as core: development of wound dressing

PubMed Central

De Marchi, João Guilherme B; Jornada, Denise S; Silva, Fernanda K; Freitas, Ana L; Fuentefria, Alexandre M; Pohlmann, Adriana R; Guterres, Silvia S

2017-01-01

The use of nanoparticles may be particularly advantageous in treating bacterial infections due to their multiple simultaneous mechanisms of action. Nanoencapsulation is particularly useful for lipophilic drugs. In this scenario, triclosan is considered a good candidate due to its lipophilicity, broad-spectrum activity, and safety. In the present study, we have developed and characterized an antimicrobial suspension of triclosan and α-bisabolol against pathogenic strains that are resistant (Pseudomonas aeruginosa) and susceptible (Escherichia coli, Staphylococcus aureus, and Candida albicans) to triclosan. We also aimed to determine the minimum inhibitory concentration, using serial microdilution adapted from a CLSI methodology (Clinical and Laboratory Standards Institute). Challenge test was used to confirm the antimicrobial effectiveness of the nanocapsule formulation, as well as after its incorporation into a commercial wound dressing (Veloderm®). The zeta potential of P. aeruginosa before and after contact with cationic nanocapsules and the ratio between the number of nanocapsules per colony forming unit (CFU) were determined to evaluate a possible interaction between nanocapsules and bacteria. The results showed that nanoencapsulation has improved the antimicrobial activity when tested with two different methodologies. The number of nanocapsules per CFU was high even in great dilutions and the zeta potential was reverted after being in contact with the cationic nanocapsules. The nanocapsules were able to improve the activity of triclosan, even when tested within 28 days and when dried in the wound dressing. PMID:29123398

Antimicrobial Activity of Novel Synthetic Peptides Derived from Indolicidin and Ranalexin against Streptococcus pneumoniae

PubMed Central

Jindal, Hassan Mahmood; Le, Cheng Foh; Mohd Yusof, Mohd Yasim; Velayuthan, Rukumani Devi; Lee, Vannajan Sanghiran; Zain, Sharifuddin Md; Isa, Diyana Mohd; Sekaran, Shamala Devi

2015-01-01

Antimicrobial peptides (AMPs) represent promising alternatives to conventional antibiotics in order to defeat multidrug-resistant bacteria such as Streptococcus pneumoniae. In this study, thirteen antimicrobial peptides were designed based on two natural peptides indolicidin and ranalexin. Our results revealed that four hybrid peptides RN7-IN10, RN7-IN9, RN7-IN8, and RN7-IN6 possess potent antibacterial activity against 30 pneumococcal clinical isolates (MIC 7.81-15.62µg/ml). These four hybrid peptides also showed broad spectrum antibacterial activity (7.81µg/ml) against S. aureus, methicillin resistant S. aureus (MRSA), and E. coli. Furthermore, the time killing assay results showed that the hybrid peptides were able to eliminate S. pneumoniae within less than one hour which is faster than the standard drugs erythromycin and ceftriaxone. The cytotoxic effects of peptides were tested against human erythrocytes, WRL-68 normal liver cell line, and NL-20 normal lung cell line. The results revealed that none of the thirteen peptides have cytotoxic or hemolytic effects at their MIC values. The in silico molecular docking study was carried out to investigate the binding properties of peptides with three pneumococcal virulent targets by Autodock Vina. RN7IN6 showed a strong affinity to target proteins; autolysin, pneumolysin, and pneumococcal surface protein A (PspA) based on rigid docking studies. Our results suggest that the hybrid peptides could be suitable candidates for antibacterial drug development. PMID:26046345

Lyophilised wafers as vehicles for the topical release of chlorhexidine digluconate--release kinetics and efficacy against Pseudomonas aeruginosa.

PubMed

Labovitiadi, Olga; Lamb, Andrew J; Matthews, Kerr H

2012-12-15

There is a requirement to deliver accurate amounts of broad spectrum antimicrobial compounds locally to exuding wounds. Varying amounts of exudate complicates this process by limiting the residence and therefore efficacy of active substances. Minimum bactericidal concentrations (MBC) of antimicrobials are necessary to suppress infection and lessen the chances of resistant strains of potentially pathogenic bacteria from prevailing. Polysaccharide wafers can adhere to exudating wound beds, absorbing fluids and forming highly viscous gels that remain in situ for prolonged periods of time to release sustained amounts of antimicrobial. In this study, five different formulations were produced containing the antimicrobial, chlorhexidine digluconate (CHD). Absorption of simulated wound fluid, resultant rheological properties of gels and efficacy against plated cultures of Pseudomonas aeruginosa were measured and compared. CHD reduced the 'water uptake' of wafers by 11-50% (w/w) and decreased the rheological consistency of non-SA containing gels by 10-65%. Release studies indicated that karaya wafers gave the highest sustained release of CHD, >60 μg/mL in 24 h, well in excess of the MBC for P. aeruginosa. Release kinetics indicated an anomalous diffusion mechanism according to Korsmeyer-Peppas, with diffusion exponents varying from 0.31 to 0.41 for most wafers except xanthan (0.65). Copyright © 2012 Elsevier B.V. All rights reserved.

Laboratory Evaluation of 3-(5-Tetrazolyl)Penam, a New Semisynthetic Beta-Lactam Antibacterial Agent with Extended Broad-Spectrum Activity

PubMed Central

English, Arthur R.; Retsema, James A.; Lynch, John E.

1976-01-01

In the new agent 3-(5-tetrazolyl)penam, hereafter referred to as CP-35,587, the carboxyl function at C3 in the penicillin nucleus has been replaced with the 5-tetrazolyl moiety. Marked changes in spectrum and resistance to gram-negative β-lactamases, particularly with regard to Klebsiella pneumoniae isolates, were conferred by this modification. The anti-Klebsiella activity clearly distinguishes the antibacterial spectrum of CP-35,587 from any known broad-spectrum penicillin. Compared to orally active cephalosporins, the spectrum advantage of CP-35,587 encompasses Enterobacter, Serratia marcescens, Citrobacter, Providencia, Haemophilus influenzae, and Streptococcus faecalis, both in vitro and in murine infections produced by many of the above-named microorganisms. Thus, CP-35,587 combines and extends the antibacterial activity of broad-spectrum penicillins and orally active cephalosporins. PMID:984745

Antimicrobial activity and self-assembly behavior of antimicrobial peptide chensinin-1b with lipophilic alkyl tails.

PubMed

Dong, Weibing; Liu, Ziang; Sun, Liying; Wang, Cui; Guan, Yue; Mao, Xiaoman; Shang, Dejing

2018-04-25

The threshold hydrophobicity and amphipathic structure of the peptidic chain are important for the biological function of antimicrobial peptides. Chensinin-1b exhibits broad-spectrum bactericidal activity with no hemolytic activity but has almost no anticancer ability against the selected cancer cell lines. In this study, the conjugation of aliphatic acid was designed with different lengths of N-terminal of chensinin-1b, the antimicrobial activity of the resulting lipo-chensinin-1b was examined, in which OA-C1b showed much stronger activity than those of cheninin-1b and the other two lipopeptides. The membrane interaction between the lipo-chensinin-1b and real/mimetic bacterial cell membrane was investigated. Electrostatic interactions between the lipo-chensinin-1b and lipopolysaccharides were detected by isothermal titration calorimetry and the binding affinities were 10.83 μM, 8.77 μM and 7.35 μM for OA-C1b, LA-C1b and PA-C1b, respectively. The antimicrobial activity and membrane interaction ability of the lipo-chensinin-1b followed this order: OA-C1b > chensinin-1b > LA-C1b > PA-C1b. In addition, the lipo-chensinin-1b also exhibited lytic activity against various cancer cells and demonstrated the ability to inhibit LPS-stimulated cytokine release from human U937 cells. The CD spectra indicated that the helical or β-strands contents were existed as the main components in TFE or LPS solution, respectively. The self-assembly behavior was trigged by the solution pH and affected by the length of carbon chain, in which chensinin-1b, OA-C1b, LA-C1b and PA-C1b formed micelles at neutral pH and the micelle size increased for chensinin-1b, OA-C1b and LA-C1b. PA-C1b formed nanofibers in an acidic environment indicated by TEM experiments, and the peptides formed aggregates in an acidic environment and re-dissociated when the pH was adjusted to neutral. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Pharmacologically significant complexes of Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) of novel Schiff base ligand, (E)-N-(furan-2-yl methylene) quinolin-8-amine: Synthesis, spectral, XRD, SEM, antimicrobial, antioxidant and in vitro cytotoxic studies

NASA Astrophysics Data System (ADS)

Shakir, M.; Hanif, Summaiya; Sherwani, Mohd. Asif; Mohammad, Owais; Al-Resayes, Saud I.

2015-07-01

A novel series of metal complexes of the types, [ML2(H2O)2]Cl2 and [ML2]Cl2 [M = Mn(II), 1; Co(II), 2; Ni(II), 3; Cu(II), 4; and Zn(II), 5] were synthesized by the interaction of ligand, L (E)-N-(furan-2-yl methylene) quinolin-8-amine, derived from the condensation of 2-furaldehyde and 8-aminoquinoline. The synthesized ligand and its metal complexes were characterized on the basis of results obtained from elemental analysis, ESI-MS, XRD, SEM, TGA/DTA, FT-IR, UV-Vis, magnetic moment and 1H and 13C NMR spectroscopic studies. EPR parameters were recorded in case of complex 4. The comparative in-vitro antimicrobial activities against various pathogens with reference to known antibiotics and antioxidant activity against standard control at variable concentrations revealed that the metal complexes show enhanced antimicrobial and free radical scavenging activities in general as compared to free ligand. However, the complexes 1 and 5 have shown best antioxidant activity among all the metal complexes. Furthermore, comparative in-vitro antiproliferative activity on ligand and its metal chelates performed on MDA-MB-231 (breast carcinoma), KCL22 (blood lymphoid carcinoma), HeLa (cervical carcinoma) cell lines and normal cells (PBMC) revealed that metal chelates show moderate to good activity as compared to ligand where as complex 1 seems to be the most promising one possessing a broad spectrum of activity against all the selected cancer cell lines with IC50 < 2.10 μM.

Emerging treatment options for acute bacterial skin and skin structure infections: focus on intravenous delafloxacin

PubMed Central

Righi, Elda; Carnelutti, Alessia; Vena, Antonio; Bassetti, Matteo

2018-01-01

The increase in hospitalization due to acute bacterial skin and skin structure infections (ABSSSI) caused by resistant pathogens supports the need for new treatment options. Antimicrobial options for ABSSSI that provide broad-spectrum coverage, including gram-negative pathogens and multidrug-resistant gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), are limited. Delafloxacin is a novel fluoroquinolone available as intravenous and oral formulations and is characterized by an increased efficacy in acidic environments and activity on bacterial biofilm. Delafloxacin displays enhanced in vitro activity against MRSA, and enterococci, while maintaining efficacy against gram-negative pathogens and anaerobes. Delafloxacin has been studied for the treatment of ABSSSI and respiratory infections. Phase III studies have demonstrated noninferiority of delafloxacin compared to vancomycin, linezolid, tigecycline, and the combination of vancomycin plus aztreonam in the treatment of ABSSSI. Due to its favorable pharmacokinetic characteristics, the wide spectrum of action, and the potential for sequential therapy, delafloxacin represents a promising option in the empirical and targeted treatment of ABSSSI, both in hospital- and in community-based care. PMID:29670380

Emerging treatment options for acute bacterial skin and skin structure infections: focus on intravenous delafloxacin.

PubMed

Righi, Elda; Carnelutti, Alessia; Vena, Antonio; Bassetti, Matteo

2018-01-01

The increase in hospitalization due to acute bacterial skin and skin structure infections (ABSSSI) caused by resistant pathogens supports the need for new treatment options. Antimicrobial options for ABSSSI that provide broad-spectrum coverage, including gram-negative pathogens and multidrug-resistant gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), are limited. Delafloxacin is a novel fluoroquinolone available as intravenous and oral formulations and is characterized by an increased efficacy in acidic environments and activity on bacterial biofilm. Delafloxacin displays enhanced in vitro activity against MRSA, and enterococci, while maintaining efficacy against gram-negative pathogens and anaerobes. Delafloxacin has been studied for the treatment of ABSSSI and respiratory infections. Phase III studies have demonstrated noninferiority of delafloxacin compared to vancomycin, linezolid, tigecycline, and the combination of vancomycin plus aztreonam in the treatment of ABSSSI. Due to its favorable pharmacokinetic characteristics, the wide spectrum of action, and the potential for sequential therapy, delafloxacin represents a promising option in the empirical and targeted treatment of ABSSSI, both in hospital- and in community-based care.

76 FR 79697 - Withdrawal of Notices of Opportunity for a Hearing; Penicillin and Tetracycline Used in Animal Feed

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-22

... antibiotic or antibacterial agent in animal feed presents a hazard to human and animal health. (Refs. 1 and 6... ``antimicrobial'' refers broadly to drugs with activity against a variety of microorganisms including: Bacteria, viruses, fungi, and parasites. Antimicrobial drugs that have specific activity against bacteria are...

Evaluation of Carbohydrate-Derived Fulvic Acid (CHD-FA) as a Topical Broad-Spectrum Antimicrobial for Drug-Resistant Wound Infections

DTIC Science & Technology

2015-10-01

resistant Klebsiella pneumoniae, Enterococcus faecium, Staphylococcus aureus, Methicillin- resistant Staphylococcus aureus (MRSA), Escherichia coli ...cutaneous wound model in rats with the drug resistant Gram negative bacteria Acinetobacter baumannii, Escherichia coli , Klebsiella pneumoniae and...bioburden reduction induced by CHD-FA was also observed in wounds infected with multidrug resistant E. coli and K. pneumoniae. To better assess wound

Bacteriocinogenic Lactococcus lactis subsp. lactis DF04Mi isolated from goat milk: Characterization of the bacteriocin

PubMed Central

Furtado, Danielle N.; Todorov, Svetoslav D.; Landgraf, Mariza; Destro, Maria T.; Franco, Bernadette D.G.M.

2014-01-01

Lactic acid bacteria capable of producing bacteriocins and presenting probiotic potential open innovative technological applications in the dairy industry. In this study, a bacteriocinogenic strain (Lactococcus lactis subsp. lactis DF4Mi) was isolated from goat milk, and studied for its antimicrobial activity. The bacteriocin presented a broad spectrum of activity, was sensitive to proteolytic enzymes, resistant to heat and pH extremes, and not affected by the presence of SDS, Tween 20, Tween 80, EDTA or NaCl. Bacteriocin production was dependent on the components of the culture media, especially nitrogen source and salts. When tested by PCR, the bacteriocin gene presented 100% homology to nisin Z gene. These properties indicate that this L. lactis subsp. lactis DF4Mi can be used for enhancement of dairy foods safety and quality. PMID:25763065

[Tetracyclines, sulfonamides and metronidazole].

PubMed

Pérez-Trallero, Emilio; Iglesias, Luis

2003-11-01

Tetracyclines form a group of natural and semisynthetic products that acts inhibiting the bacterial protein synthesis. They are bacteriostatic agents, exhibiting activity against a wide range of organisms, but they are at the present of limited use because of their acquired resistance. Doxycycline is currently the most frequently used tetracycline in human medicine and it is included in the List of Essential Medicines of the World Health Organization. Sulfonamides are synthetic, broad-spectrum bacteriostatic antibiotics. They were the first effective systemic antimicrobial agents. Their mode of action is based on the inhibition of DNA synthesis. Due to their toxicity and high adquired resistance their use is currently very low. Metronidazole is the main compound of 5-nitroimidazole family. It is a very active bactericidal antibiotic against anaerobic and some microaerophilic bacteria and it is still very useful in the treatment of bacterian and parasitic infections.

Resistance to bacteriocins produced by Gram-positive bacteria.

PubMed

Bastos, Maria do Carmo de Freire; Coelho, Marcus Lívio Varella; Santos, Olinda Cabral da Silva

2015-04-01

Bacteriocins are prokaryotic proteins or peptides with antimicrobial activity. Most of them exhibit a broad spectrum of activity, inhibiting micro-organisms belonging to different genera and species, including many bacterial pathogens which cause human, animal or plant infections. Therefore, these substances have potential biotechnological applications in either food preservation or prevention and control of bacterial infectious diseases. However, there is concern that continuous exposure of bacteria to bacteriocins may select cells resistant to them, as observed for conventional antimicrobials. Based on the models already investigated, bacteriocin resistance may be either innate or acquired and seems to be a complex phenomenon, arising at different frequencies (generally from 10(-9) to 10(-2)) and by different mechanisms, even amongst strains of the same bacterial species. In the present review, we discuss the prevalence, development and molecular mechanisms involved in resistance to bacteriocins produced by Gram-positive bacteria. These mechanisms generally involve changes in the bacterial cell envelope, which result in (i) reduction or loss of bacteriocin binding or insertion, (ii) bacteriocin sequestering, (iii) bacteriocin efflux pumping (export) and (iv) bacteriocin degradation, amongst others. Strategies that can be used to overcome this resistance are also addressed. © 2015 The Authors.

Resurrecting Inactive Antimicrobial Peptides from the Lipopolysaccharide Trap

PubMed Central

Mohanram, Harini

2014-01-01

Host defense antimicrobial peptides (AMPs) are a promising source of antibiotics for the treatment of multiple-drug-resistant pathogens. Lipopolysaccharide (LPS), the major component of the outer leaflet of the outer membrane of Gram-negative bacteria, functions as a permeability barrier against a variety of molecules, including AMPs. Further, LPS or endotoxin is the causative agent of sepsis killing 100,000 people per year in the United States alone. LPS can restrict the activity of AMPs inducing aggregations at the outer membrane, as observed for frog AMPs, temporins, and also in model AMPs. Aggregated AMPs, “trapped” by the outer membrane, are unable to traverse the cell wall, causing their inactivation. In this work, we show that these inactive AMPs can overcome LPS-induced aggregations while conjugated with a short LPS binding β-boomerang peptide motif and become highly bactericidal. The generated hybrid peptides exhibit activity against Gram-negative and Gram-positive bacteria in high-salt conditions and detoxify endotoxin. Structural and biophysical studies establish the mechanism of action of these peptides in LPS outer membrane. Most importantly, this study provides a new concept for the development of a potent broad-spectrum antibiotic with efficient outer membrane disruption as the mode of action. PMID:24419338

The antimicrobial potential of algicolous marine fungi for counteracting multidrug-resistant bacteria: phylogenetic diversity and chemical profiling.

PubMed

Gnavi, Giorgio; Palma Esposito, Fortunato; Festa, Carmen; Poli, Anna; Tedesco, Pietro; Fani, Renato; Monti, Maria Chiara; de Pascale, Donatella; D'Auria, Maria Valeria; Varese, Giovanna Cristina

2016-01-01

Marine fungi represent an important but still largely unexplored source of novel and potentially bioactive secondary metabolites. The antimicrobial activity of nine sterile mycelia isolated from the green alga Flabellia petiolata collected from the Mediterranean Sea was tested on four antibiotic-resistant bacterial strains using extracellular and intracellular extracts obtained from each fungal strain. The isolated fungi were identified at the molecular level and assigned to one of the Dothideomycetes, Sordariomycetes or Eurotiomycetes classes. Following assessment of inhibition of bacterial growth (IC50), all crude extracts were subjected to preliminary (1)H NMR and TLC analysis. According to preliminary pharmacologic and spectroscopic/chromatographic results, extracts of fungal strains MUT 4865, classified as Beauveria bassiana, and MUT 4861, classified as Microascacea sp.2, were selected for LC-HRMS analysis. Chemical profiling of antibacterial extracts from MUT 4861 and MUT 4865 by LC HRMS allowed identification of the main components of the crude extracts. Several sphingosine bases were identified, including a compound previously unreported from natural sources, which gave a rationale to the broad spectrum of antibacterial activity exhibited. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

[In vitro and in vivo activities of sulopenem compared with those of imipenem and cephalosporins].

PubMed

Nagashima, M; Goto, S; Yoshida, T; Matsunaga, T; Shimohira, H; Ogawa, M

1996-04-01

The in vitro and in vivo antibacterial activities of sulopenem (CP-70,429),a new parenteral penem antibiotic, were compared with those of imipenem (IPM), flomoxef, cefuzonam (CZON) and cefotaxime. Sulopenem possessed broad-spectrum activities against Gram-positive bacteria and Gram-negative bacteria. Antibacterial activities of sulopenem against methicillin-sensitive Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pyogenes and Streptococcus pneumoniae were equivalent to or somewhat superior to those of IPM. Against members of the family Enterobacteriaceae, sulopenem was 4- to 260-fold more active than reference antibiotics with broad-spectra. In a killing kinetics study for Haemophilus influenzae, sulopenem showed a 99.9% decrease of viable cells after 8 hours at a concentration of 0.20 micrograms/ml. This effect was obtained at a concentration 8-fold lower than that of IPM. The protective effects of sulopenem in murine experimental systemic infections were superior to those of imipenem/cilastatin. In murine experimental mixed infection with Escherichia coli and Bacteroides fragilis, sulopenem had lower ED50, in other words stronger antimicrobial activities than IPM. The therapeutic effect of sulopenem are related well with its MIC value. In guinea pigs experimental lung infection with Klebsiella pneumoniae, sulopenem was more effective than CZON or cefotiam.

Antimicrobial Treatment of Polymeric Medical Devices by Silver Nanomaterials and Related Technology

PubMed Central

Polívková, Markéta; Hubáček, Tomáš; Staszek, Marek; Švorčík, Václav; Siegel, Jakub

2017-01-01

Antimicrobial biocompatible polymers form a group of highly desirable materials in medicinal technology that exhibit interesting thermal and mechanical properties, and high chemical resistance. There are numerous types of polymers with antimicrobial activity or antimicrobial properties conferred through their proper modification. In this review, we focus on the second type of polymers, especially those whose antimicrobial activity is conferred by nanotechnology. Nanotechnology processing is a developing area that exploits the antibacterial effects of broad-scale compounds, both organic and inorganic, to form value-added medical devices. This work gives an overview of nanostructured antimicrobial agents, especially silver ones, used together with biocompatible polymers as effective antimicrobial composites in healthcare. The bactericidal properties of non-conventional antimicrobial agents are compared with those of conventional ones and the advantages and disadvantages are discussed. PMID:28212308

[Antimicrobial activity of Laetiporus sulphureus strains grown in submerged culture].

PubMed

Ershova, E Iu; Tikhonova, O V; Lur'e, L M; Efremenkova, O V; Kamzolkina, O V; Dudnik, Iu V

2003-01-01

Cultural conditions for growth and fruit body formation were elaborated to four strains of Laetiporus sulphureus isolated from nature. All strains demonstrated antimicrobial activity against a wide spectrum of gram-positive and gram-negative bacteria during agar and submerged cultivation including methicillin-resistant strain of Staphylococcus aureus (MRSA) and glycopeptide-resistant strain of Leuconostoc mesenteroides. Antifungal activity was not found. The level of antimicrobial activity during submerged cultivation reached maximum after seven days of growth on specific medium with soybean meal and corn liquid; the next four weeks its increasing was not so manifested. Antimicrobial activity correlated with orange pigment secretion and cultural liquid acidification to pH 2.0-2.8 that indicates on acid nature of synthesized products.

Evaluation of free or anchored antimicrobial peptides as candidates for the prevention of orthopaedic device-related infections.

PubMed

D'Este, Francesca; Oro, Debora; Boix-Lemonche, Gerard; Tossi, Alessandro; Skerlavaj, Barbara

2017-10-01

The prevention of implant-associated infection, one the most feared complications in orthopaedic surgery, remains a major clinical challenge and urges development of effective methods to prevent bacterial colonization of implanted devices. Alpha-helical antimicrobial peptides (AMPs) may be promising candidates in this respect due to their potent and broad-spectrum antimicrobial activity, their low tendency to elicit resistance and possible retention of efficacy in the immobilized state. The aim of this study was to evaluate the potential of five different helical AMPs, the cathelicidins BMAP-27 and BMAP-28, their (1-18) fragments and the rationally designed, artificial P19(9/G7) peptide, for the prevention of orthopaedic implant infections. Peptides were effective at micromolar concentrations against 22 Staphylococcus and Streptococcus isolates from orthopaedic infections, while only BMAP-28 and to a lesser extent BMAP-27 were active against Enterococcus faecalis. Peptides in solution showed activities comparable to those of cefazolin and linezolid, on a molar basis, and also a variable capacity to neutralize bacterial lipopolysaccharide, while devoid of adverse effects on MG-63 osteoblast cells at concentrations corresponding to the MIC. The (1-18) BMAP fragments and P19(9/G7) were selected for further examination, based on better selectivity indices, and showed effectiveness in the presence of hyaluronic acid and in synovial fluid, while human serum affected their activity to variable extents, with BMAP-27(1-18) best retaining activity. This peptide was immobilized on streptavidin-resin beads and retained activity against reference Staphylococcus epidermidis and Staphylococcus aureus strains, with negligible toxicity towards osteoblasts, underlining its potential for the development of infection-resistant biomaterials for orthopaedic application. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Perspectives and Peptides of the Next Generation

NASA Astrophysics Data System (ADS)

Brogden, Kim A.

Shortly after their discovery, antimicrobial peptides from prokaryotes and eukaryotes were recognized as the next potential generation of pharmaceuticals to treat antibiotic-resistant bacterial infections and septic shock, to preserve food, or to sanitize surfaces. Initial research focused on identifying the spectrum of antimicrobial agents, determining the range of antimicrobial activities against bacterial, fungal, and viral pathogens, and assessing the antimicrobial activity of synthetic peptides versus their natural counterparts. Subsequent research then focused on the mechanisms of antimicrobial peptide activity in model membrane systems not only to identify the mechanisms of antimicrobial peptide activity in microorganisms but also to discern differences in cytotoxicity for prokaryotic and eukaryotic cells. Recent, contemporary work now focuses on current and future efforts to construct hybrid peptides, peptide congeners, stabilized peptides, peptide conjugates, and immobilized peptides for unique and specific applications to control the growth of microorganisms in vitro and in vivo.

An alternate pathophysiologic paradigm of sepsis and septic shock

PubMed Central

Kumar, Anand

2014-01-01

The advent of modern antimicrobial therapy following the discovery of penicillin during the 1940s yielded remarkable improvements in case fatality rate of serious infections including septic shock. Since then, pathogens have continuously evolved under selective antimicrobial pressure resulting in a lack of significant improvement in clinical effectiveness in the antimicrobial therapy of septic shock despite ever more broad-spectrum and potent drugs. In addition, although substantial effort and money has been expended on the development novel non-antimicrobial therapies of sepsis in the past 30 years, clinical progress in this regard has been limited. This review explores the possibility that the current pathophysiologic paradigm of septic shock fails to appropriately consider the primacy of the microbial burden of infection as the primary driver of septic organ dysfunction. An alternate paradigm is offered that suggests that has substantial implications for optimizing antimicrobial therapy in septic shock. This model of disease progression suggests the key to significant improvement in the outcome of septic shock may lie, in great part, with improvements in delivery of existing antimicrobials and other anti-infectious strategies. Recognition of the role of delays in administration of antimicrobial therapy in the poor outcomes of septic shock is central to this effort. However, therapeutic strategies that improve the degree of antimicrobial cidality likely also have a crucial role. PMID:24184742

Antimicrobial action of an endophytic fungi from Sophor flavescens and structure identification of its active constituent

PubMed Central

Yu, Na; He, Lu; Liu, Na; Wang, Yong; Xu, Hongbo; Liu, Dandan

2014-01-01

Endophytic fungus BS002 was isolated and characterized from Sophora flavescens by plate method, which has broad antimicrobial activity. Isolation and trace of a new bioactive compound from the fungus’ culture extracts with the method of column chromatography and TLC biological autoradiography was conducted. Finally, it was identified as 6,7-(2′E) dibutenyl-5,8-dihydroxy-(Z)-cyclooct-2-ene-1,4-dione by nuclear magnetic resonance, infrared and liquid chromatography–mass spectrometry. The compound presented strong antifungal activities for example: Botryosphaeria berengriana f.sp. piricola, Physalospora piricola, Cladosporium cucumerinum Ell. Arthur., Fusarium oxysporum f.sp. cucumerinum, Fusarium moniliforme. The inhibition to Physalospora piricola was the strongest with an antibacterial diameter of 45 mm. This paper is the first report of the antimicrobial activity of endophytic fungi BS002 that was the secondary metabolites extracted from the seeds of Sophora flavescens. The results provide a broad foreground for biopharmaceuticals and biopesticide. PMID:26019517

Characterization of a novel antibacterial glycopeptide produced by Penicillium sp. M03.

PubMed

Yang, W H; Zhang, W C; Lu, X M; Jiang, G S; Gao, P J

2009-04-01

To isolate a novel antibiotic termed AF from fermentation broth of Penicillium sp. M03 and to examine its antimicrobial activity, biological properties and structure characteristics. Sephadex LH-20 and HPLC were used to purify AF from fermentation broth of Penicillium sp. M03. The antimicrobial activity of AF was evaluated with the agar diffusion test. Amino acid and monosaccharide composition of AF was analysed by a HITACHI 835 detector and HPLC assay, respectively. Matrix-assisted laser desorption time of flight mass spectrometry, FT-IR and (1)H nuclear magnetic resonance spectra analyses were performed to examine the initial structure of AF. Eighty milligrams of AF was isolated as white powder from 1-l Penicillium sp. M03 fermentation broth. It consists of five amino acid and two monosaccharide residues and the molecular weight of it was 1017, and it was stable to beta-lactamase, heat, acid and alkali. AF showed inhibitory activity to a wide range of bacteria, particularly to multidrug-resistant Staphylococcus aureus. AF was a novel antibacterial glycopeptide with a broad inhibitory spectrum to pathogenic bacteria including multidrug-resistant agents. Furthermore, it is difficult to generate bacteria resistant to AF. Characterization of AF made it a potential antibiotic to fight against antibiotic-resistant bacterial pathogens.

Are there any reasons to change our behavior in necrotizing fasciitis with the advent of new antibiotics?

PubMed

Menichetti, Francesco; Giuliano, Simone; Fortunato, Simona

2017-04-01

The treatment of necrotizing fasciitis requires a multifaceted approach, consisting of surgical source control with immediate surgical debridement along with life support, clinical monitoring, and antimicrobial therapy. Many drugs are now available for the treatment of this life-threatening infectious disease, and the purpose of this review is to provide the reader with an updated overview of the newest therapeutic options. Because most necrotizing soft tissue infections are polymicrobial, broad-spectrum coverage is advisable. Acceptable monotherapy regimens include piperacillin-tazobactam or a carbapenem. However, drugs such as ceftolozane-tazobactam, ceftazidime-avibactam in association with an antianaerobic agent (metronidazole or clindamycin) are currently available as valuable alternatives. The new cephalosporins active against methicillin-resistant Staphylococcus aureus (MRSA), ceftaroline, and ceftobiprole share similar antibacterial activity against Gram-positive cocci, and they might be considered as an alternative to nonbetalactam anti-MRSA agents for necrotizing fasciitis management. Two new long-acting lypoglycopeptides - oritavancin and dalbavancin - share the indications for acute bacterial skin and skin structure infections and had similar activity against Gram-positive cocci including MRSA and streptococci. Carbapenem-sparing agents are particularly suitable for antimicrobial stewardship strategy. The new long-acting lypoglycopeptides are very effective in treating necrotizing fasciitis and are uttermost attractive for patients requiring short hospital stays and early discharge.

Antimicrobial activity of ceftaroline and other anti-infective agents against microbial pathogens recovered from the surgical intensive care patient population: a prevalence analysis.

PubMed

Edmiston, Charles E; Krepel, Candace J; Leaper, David; Ledeboer, Nathan A; Mackey, Tami-Lea; Graham, Mary Beth; Lee, Cheong; Rossi, Peter J; Brown, Kellie R; Lewis, Brian D; Seabrook, Gary R

2014-12-01

Ceftaroline is a new parenteral cephalosporin agent with excellent activity against methicillin-sensitive (MSSA) and resistant strains of Staphylococcus aureus (MRSA). Critically ill surgical patients are susceptible to infection, often by multi-drug-resistant pathogens. The activity of ceftaroline against such pathogens has not been described. Three hundred thirty-five consecutive microbial isolates were collected from surgical wounds or abscesses, respiratory, urine, and blood cultures from patients in the surgical intensive care unit (SICU) of a major tertiary medical center. Using Clinical and Laboratory Standards Institute (CLSI) standard methodology and published breakpoints, all aerobic, facultative anaerobic isolates were tested against ceftaroline and selected comparative antimicrobial agents. All staphylococcal isolates were susceptible to ceftaroline at a breakpoint of ≤1.0 mcg/mL. In addition, ceftaroline exhibited excellent activity against all streptococcal clinical isolates and non-ESBL-producing strains of Enterobacteriaceae (93.5%) recovered from SICU patients. Ceftaroline was inactive against ESBL-producing Enterobacteriaceae, Pseudomonas aeruginosa, vancomycin-resistant enterococci, and selective gram-negative anaerobic bacteria. At present, ceftaroline is the only cephalosporin agent that is active against community and healthcare-associated MRSA. Further studies are needed to validate the benefit of this novel broad-spectrum anti-infective agent for the treatment of susceptible serious infections in the SICU patient population.

Characterization of some bacteriocins produced by lactic acid bacteria isolated from fermented foods.

PubMed

Grosu-Tudor, Silvia-Simona; Stancu, Mihaela-Marilena; Pelinescu, Diana; Zamfir, Medana

2014-09-01

Lactic acid bacteria (LAB) isolated from different sources (dairy products, fruits, fresh and fermented vegetables, fermented cereals) were screened for antimicrobial activity against other bacteria, including potential pathogens and food spoiling bacteria. Six strains have been shown to produce bacteriocins: Lactococcus lactis 19.3, Lactobacillus plantarum 26.1, Enterococcus durans 41.2, isolated from dairy products and Lactobacillus amylolyticus P40 and P50, and Lactobacillus oris P49, isolated from bors. Among the six bacteriocins, there were both heat stable, low molecular mass polypeptides, with a broad inhibitory spectrum, probably belonging to class II bacteriocins, and heat labile, high molecular mass proteins, with a very narrow inhibitory spectrum, most probably belonging to class III bacteriocins. A synergistic effect of some bacteriocins mixtures was observed. We can conclude that fermented foods are still important sources of new functional LAB. Among the six characterized bacteriocins, there might be some novel compounds with interesting features. Moreover, the bacteriocin-producing strains isolated in our study may find applications as protective cultures.

Clinical and pharmacokinetic drug evaluation of delafloxacin for the treatment of acute bacterial skin and skin structure infections.

PubMed

Bassetti, Matteo; Pecori, Davide; Cojutti, Piergiorgio; Righi, Elda; Pea, Federico

2017-11-01

In the era of multi-drug resistant pathogens, the adequate treatment of skin and skin structure infections remains a challenge for clinicians. Delafloxacin, with its broad spectrum against Gram-positive, Gram-negative and anaerobic organisms, represents a new therapeutic option in this setting, especially when coverage of methicillin-resistant Staphylococcus aureus is required in the empirical or targeted approach. Areas covered: In this drug evaluation, the Authors have reviewed the pharmacokinetic and pharmacodynamic characteristics of delafloxacin. In addition, recent data on clinical efficacy and safety from clinical trials have been included. Expert opinion: Delafloxacin represents an attractive therapeutic option due to a broad antimicrobial and favorable pharmacokinetic and pharmacodynamic profile. Several in vitro studies have demonstrated the low potential for resistance selection if used in empirical regimens. Delafloxacin is a promising candidate for the treatment of Gram-positive infections, especially if co-infection with other pathogens is suspected. This is because of the very low MIC of the agent for Gram-positive (including MRSA) and anaerobic bacteria and because of the wide spectrum of activity against Gram-negative organisms. For these interesting microbiological and PK/PD characteristics we expect future uses of this drug in other indications such as diabetic foot infection, osteomyelitis, prosthetic joint infections, abdominal infections and central nervous system infections.

Mussel-inspired synthesis of polydopamine-functionalized graphene oxide hydrogel as broad-spectrum antimicrobial material

NASA Astrophysics Data System (ADS)

Wang, Xinpeng; Liu, Zhiming; Zhong, Huiqing; Guo, Zhouyi; Yuan, Xiaochan

2014-09-01

Recently, three-dimensional GO-based hydrogels have attracted great attention due to the unique advantages. It is generally know that bacteria are everywhere and many of them could cause the diseases and threaten human health. However, developing new antibacterial materials with high-efficiency, low cost, broad-spectrum, and easy recycling is still a great challenge. Herein, inspired by mussel, we synthesized benzalkonium bromide/polydopamine/reduced graphene oxide hydrogel (BKB/PDA/rGOG). The as-prepared three-dimensional hydrogels were characterized by scanning eletron microscope (SEM), Fourier transform infrared spectroscopy (FT-IR) and Raman spectroscopy. The resultant hydrogels exhibited strong antibacterial effects to both Gram-negative and Gram-positive bacteria due to the synergistic effect of graphene oxide and benzalkonium bromide. In addition, the resultant hydrogels could be removed easily from the resolution, which was undoubtedly good news for industry application.

The value and validation of broad spectrum biosensors for diagnosis and biodefense

PubMed Central

Metzgar, David; Sampath, Rangarajan; Rounds, Megan A; Ecker, David J

2013-01-01

Broad spectrum biosensors capable of identifying diverse organisms are transitioning from the realm of research into the clinic. These technologies simultaneously capture signals from a wide variety of biological entities using universal processes. Specific organisms are then identified through bioinformatic signature-matching processes. This is in contrast to currently accepted molecular diagnostic technologies, which utilize unique reagents and processes to detect each organism of interest. This paradigm shift greatly increases the breadth of molecular diagnostic tools with little increase in biochemical complexity, enabling simultaneous diagnostic, epidemiologic, and biothreat surveillance capabilities at the point of care. This, in turn, offers the promise of increased biosecurity and better antimicrobial stewardship. Efficient realization of these potential gains will require novel regulatory paradigms reflective of the generalized, information-based nature of these assays, allowing extension of empirical data obtained from readily available organisms to support broader reporting of rare, difficult to culture, or extremely hazardous organisms. PMID:24128433

A novel peptide with potent and broad-spectrum antiviral activities against multiple respiratory viruses

PubMed Central

Zhao, Hanjun; Zhou, Jie; Zhang, Ke; Chu, Hin; Liu, Dabin; Poon, Vincent Kwok-Man; Chan, Chris Chung-Sing; Leung, Ho-Chuen; Fai, Ng; Lin, Yong-Ping; Zhang, Anna Jin-Xia; Jin, Dong-Yan; Yuen, Kwok-Yung; Zheng, Bo-Jian

2016-01-01

A safe, potent and broad-spectrum antiviral is urgently needed to combat emerging respiratory viruses. In light of the broad antiviral activity of β-defensins, we tested the antiviral activity of 11 peptides derived from mouse β-defensin-4 and found that a short peptide, P9, exhibited potent and broad-spectrum antiviral effects against multiple respiratory viruses in vitro and in vivo, including influenza A virus H1N1, H3N2, H5N1, H7N7, H7N9, SARS-CoV and MERS-CoV. The antiviral activity of P9 was attributed to its high-affinity binding to viral glycoproteins, as well as the abundance of basic amino acids in its composition. After binding viral particles through viral surface glycoproteins, P9 entered into cells together with the viruses via endocytosis and prevented endosomal acidification, which blocked membrane fusion and subsequent viral RNA release. This study has paved the avenue for developing new prophylactic and therapeutic agents with broad-spectrum antiviral activities. PMID:26911565

Improving antimicrobial prescribing in Irish primary care through electronic data collection and surveillance: a feasibility study.

PubMed

Galvin, Sandra; Callan, Aoife; Cormican, Martin; Duane, Sinead; Bennett, Kathleen; Murphy, Andrew W; Vellinga, Akke

2015-07-02

The increase in the spread of antimicrobial resistance (AMR) in bacterial pathogens and limited availability of new antimicrobials places immense pressure on general practitioners (GPs) to prescribe appropriately. Currently, electronic antimicrobial prescribing data is not routinely collected from GPs in Ireland for surveillance purposes to assess regional specific fluctuations or trends in antimicrobial prescribing. The current study aimed to address this issue by assessing the feasibility of remotely extracting antimicrobial prescribing data from primary care practices in Ireland, for the purpose of assessing prescribing quality using the European Surveillance of Antimicrobial Consumption (ESAC) drug specific quality indicators. Participating practices (n = 30) uploaded data to the Irish Primary Care Research Network (IPCRN). The IPCRN data extraction facility is integrated within the practice patient management software system and permitted the extraction of anonymised patient prescriptions for a one year period, from October 2012 to October 2013. The quality of antimicrobial prescribing was evaluated using the twelve ESAC drug specific quality indicators using the defined daily dose (DDD) per 1,000 inhabitants per day (DID) methodology. National and European prescribing surveillance data (based on total pharmacy sales) was obtained for a comparative analysis. Antimicrobial prescriptions (n = 57,079) for 27,043 patients were obtained from the thirty study practices for a one year period. On average, study practices prescribed a greater proportion of quinolones (37 % increase), in summer compared with winter months, a variation which was not observed in national and European data. In comparison with national data, study practices prescribed higher proportions of β-lactamase-sensitive penicillins (4.98 % vs. 4.3 %) and a greater use of broad spectrum compared to narrow-spectrum antimicrobials (ratio = 9.98 vs. 6.26) was observed. Study practices exceeded the European mean for prescribing combinations of penicillins, including β-lactamase inhibitors. This research demonstrates the feasibility and potential use of direct data extraction of anonymised practice data directly through the patient management software system. The data extraction methods described can facilitate the provision of routinely collected data for sustained and inclusive surveillance of antimicrobial prescribing. These comparisons may initiate further improvements in antimicrobial prescribing practices by identifying potential areas for improvement.

Mechanically robust and transparent N-halamine grafted PVA-co-PE films with renewable antimicrobial activity

USDA-ARS?s Scientific Manuscript database

Antimicrobial polymeric films that are both mechanically robust and function renewable would have broad technological implications for areas ranging from medical safety and bioengineering to foods industry; however, creating such materials has proven extremely challenging. Here, a novel strategy is ...

Antimicrobial acrylic materials with in situ generated silver nanoparticles.

PubMed

Oei, James D; Zhao, William W; Chu, Lianrui; DeSilva, Mauris N; Ghimire, Abishek; Rawls, H Ralph; Whang, Kyumin

2012-02-01

Polymethyl methacrylate (PMMA) is widely used to treat traumatic head injuries (cranioplasty) and orthopedic injuries (bone cement), but there is a problem with implant-centered infections. With organisms such as Acinetobacter baumannii and methicillin-resistant staphylococcus aureus developing resistance to antibiotics, there is a need for novel antimicrobial delivery mechanisms without risk of developing resistant organisms. To develop a novel antimicrobial implant material by generating silver nanoparticles (AgNP) in situ in PMMA. All PMMA samples with AgNP's (AgNP-PMMA) released Ag(+) ions in vitro for over 28 days. In vitro antimicrobial assays revealed that these samples (even samples with the slowest release rate) inhibited 99.9% of bacteria against four different strains of bacteria. Long-term antimicrobial assay showed a continued antibacterial effect past 28 days. Some AgNP-loaded PMMA groups had comparable Durometer-D hardness (a measure of degree of cure) and modulus to control PMMA, but all experimental groups had slightly lower ultimate transverse strengths. AgNP-PMMA demonstrated a tremendously broad-spectrum and long-intermediate-term antimicrobial effect with comparable mechanical properties to control PMMA. Current efforts are focused on further improving mechanical properties by reducing AgNP loading and assessing fatigue properties. Copyright © 2011 Wiley Periodicals, Inc.

Synthesis, Characterization, and In Vivo Efficacy of Shell Cross-Linked Nanoparticle Formulations Carrying Silver Antimicrobials as Aerosolized Therapeutics

PubMed Central

2014-01-01

The use of nebulizable, nanoparticle-based antimicrobial delivery systems can improve efficacy and reduce toxicity for treatment of multi-drug-resistant bacteria in the chronically infected lungs of cystic fibrosis patients. Nanoparticle vehicles are particularly useful for applying broad-spectrum silver-based antimicrobials, for instance, to improve the residence time of small-molecule silver carbene complexes (SCCs) within the lung. Therefore, we have synthesized multifunctional, shell cross-linked knedel-like polymeric nanoparticles (SCK NPs) and capitalized on the ability to independently load the shell and core with silver-based antimicrobial agents. We formulated three silver-loaded variants of SCK NPs: shell-loaded with silver cations, core-loaded with SCC10, and combined loading of shell silver cations and core SCC10. All three formulations provided a sustained delivery of silver over the course of at least 2–4 days. The two SCK NP formulations with SCC10 loaded in the core each exhibited excellent antimicrobial activity and efficacy in vivo in a mouse model of Pseudomonas aeruginosa pneumonia. SCK NPs with shell silver cation-load only, while efficacious in vitro, failed to demonstrate efficacy in vivo. However, a single dose of core SCC10-loaded SCK NPs (0.74 ± 0.16 mg Ag) provided a 28% survival advantage over sham treatment, and administration of two doses (0.88 mg Ag) improved survival to 60%. In contrast, a total of 14.5 mg of Ag+ delivered over 5 doses at 12 h intervals was necessary to achieve a 60% survival advantage with a free-drug (SCC1) formulation. Thus, SCK NPs show promise for clinical impact by greatly reducing antimicrobial dosage and dosing frequency, which could minimize toxicity and improve patient adherence. PMID:23718195

The efficacy of combined therapy with metronidazole and broad-spectrum antibiotics on postoperative outcomes for pediatric patients with perforated appendicitis

PubMed Central

Shang, Qingjuan; Geng, Qiankun; Zhang, Xuebing; Guo, Chunbao

2017-01-01

Abstract The aim of this study was to evaluate the efficacy of combined therapy with metronidazole and broad-spectrum antibiotics for patients with perforated appendicitis who underwent surgical intervention. Broad-spectrum antibiotic therapy is warranted in the treatment of perforated appendicitis. Metronidazole has been used as anaerobic antimicrobial therapy. However, few studies about the use of metronidazole in perforated appendicitis have been reported. The medical records of 249 patients treated with metronidazole combined with broad-spectrum antibiotics following perforated appendicitis surgery were reviewed retrospectively and compared with the medical records of 149 patients treated only with broad-spectrum antibiotics. Propensity score matching was performed to adjust for selected baseline variables. Clinical outcomes, including postoperative complications and length of hospital stay, were compared between the 2 groups. No differences were found between the use of combined therapy with metronidazole and the use of solely broad-spectrum antibiotic agents with regard to postoperative duration of intravenous antibiotic treatment (6.8 ± 1.3 vs 7.9 ± 2.1 days, respectively, P = .18), inflammation variables at POD 5 (white blood cell [WBC] [risk ratio [RR], 1.06; 95% confidence interval [CI], 0.67–1.93, P = .15] and C-reactive protein [CRP] [RR, 1.18; 95% CI, 0.73–2.25, P = .36]) (Table 2), and the mean postoperative length of hospital stay (LOS) (RR, 0.68, 95% CI, 0.41–0.94, P = .41). There were also no differences in the incidence of postoperative complications, including the intra-abdominal or pelvic abscess rate (7[7.1%] vs 9[9.2%], respectively, P = .40), the incidence of wound infection (14[14.3%] vs 15[15.3%], respectively, P = .50), and the 30-day readmission rate (9[9.2%] vs 12[12.2%], respectively, P = .32). Regarding overall postoperative outcomes and complications, our study demonstrated no beneficial clinical effects of metronidazole administration in patients with perforated appendicitis who underwent surgical intervention. Therefore, metronidazole is not indicated when broad-spectrum antibiotics such as aminopenicillins with β-lactam inhibitors or carbapenems and select cephalosporins are used. PMID:29381994

The efficacy of combined therapy with metronidazole and broad-spectrum antibiotics on postoperative outcomes for pediatric patients with perforated appendicitis.

PubMed

Shang, Qingjuan; Geng, Qiankun; Zhang, Xuebing; Guo, Chunbao

2017-11-01

The aim of this study was to evaluate the efficacy of combined therapy with metronidazole and broad-spectrum antibiotics for patients with perforated appendicitis who underwent surgical intervention.Broad-spectrum antibiotic therapy is warranted in the treatment of perforated appendicitis. Metronidazole has been used as anaerobic antimicrobial therapy. However, few studies about the use of metronidazole in perforated appendicitis have been reported.The medical records of 249 patients treated with metronidazole combined with broad-spectrum antibiotics following perforated appendicitis surgery were reviewed retrospectively and compared with the medical records of 149 patients treated only with broad-spectrum antibiotics. Propensity score matching was performed to adjust for selected baseline variables. Clinical outcomes, including postoperative complications and length of hospital stay, were compared between the 2 groups.No differences were found between the use of combined therapy with metronidazole and the use of solely broad-spectrum antibiotic agents with regard to postoperative duration of intravenous antibiotic treatment (6.8 ± 1.3 vs 7.9 ± 2.1 days, respectively, P = .18), inflammation variables at POD 5 (white blood cell [WBC] [risk ratio [RR], 1.06; 95% confidence interval [CI], 0.67-1.93, P = .15] and C-reactive protein [CRP] [RR, 1.18; 95% CI, 0.73-2.25, P = .36]) (Table 2), and the mean postoperative length of hospital stay (LOS) (RR, 0.68, 95% CI, 0.41-0.94, P = .41). There were also no differences in the incidence of postoperative complications, including the intra-abdominal or pelvic abscess rate (7[7.1%] vs 9[9.2%], respectively, P = .40), the incidence of wound infection (14[14.3%] vs 15[15.3%], respectively, P = .50), and the 30-day readmission rate (9[9.2%] vs 12[12.2%], respectively, P = .32).Regarding overall postoperative outcomes and complications, our study demonstrated no beneficial clinical effects of metronidazole administration in patients with perforated appendicitis who underwent surgical intervention. Therefore, metronidazole is not indicated when broad-spectrum antibiotics such as aminopenicillins with β-lactam inhibitors or carbapenems and select cephalosporins are used. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Biosynthesis of silver nanoparticles from Catharanthus roseus leaf extract and assessing their antioxidant, antimicrobial, and wound-healing activities.

PubMed

Al-Shmgani, Hanady S A; Mohammed, Wasnaa H; Sulaiman, Ghassan M; Saadoon, Ali H

2017-09-01

Biosynthesis of silver nanoparticles (AgNPs) from Catharanthus roseus leaf extract was carried out, and their characterization, as well as antioxidant, antimicrobial, and wound-healing activities were evaluated. Color change, UV-vis spectrum, XRD, FTIR, and AFM assessments supported the biosynthesis and characterization of AgNPs. The synthesized AgNPs showed strong in vitro antioxidant and antimicrobial activities against various pathogens. The in vivo assessment of wound healing in AgNPs-treated mice revealed their effectiveness in closuring and reducing size of wounds. Such potent bioactivity may justify their biomedical use as antioxidant and antimicrobial agents for controlling various health-related diseases, particularly in wound healing.

Antimicrobial Activity and Mechanism of Inhibition of Silver Nanoparticles against Extreme Halophilic Archaea.

PubMed

Thombre, Rebecca S; Shinde, Vinaya; Thaiparambil, Elvina; Zende, Samruddhi; Mehta, Sourabh

2016-01-01

Haloarchaea are salt-loving halophilic microorganisms that inhabit marine environments, sea water, salterns, and lakes. The resistance of haloarchaea to physical extremities that challenge organismic survival is ubiquitous. Metal and antibiotic resistance of haloarchaea has been on an upsurge due to the exposure of these organisms to metal sinks and drug resistance genes augmented in their natural habitats due to anthropogenic activities and environmental pollution. The efficacy of silver nanoparticles (SNPs) as a potent and broad spectrum inhibitory agent is known, however, there are no reports on the inhibitory activity of SNPs against haloarchaea. In the present study, we have investigated the antimicrobial potentials of SNPs synthesized using aqueous leaf extract of Cinnamomum tamala against antibiotic resistant haloarchaeal isolates Haloferax prahovense RR8, Haloferax lucentense RR15, Haloarcula argentinensis RR10 and Haloarcula tradensis RR13. The synthesized SNPs were characterized by UV-Vis spectroscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy, dynamic light scattering, X-ray diffraction and Fourier transform infrared spectroscopy. The SNPs demonstrated potent antimicrobial activity against the haloarchaea with a minimum inhibitory concentration of 300-400 μg/ml. Growth kinetics of haloarchaea in the presence of SNPs was studied by employing the Baranyi mathematical model for microbial growth using the DMFit curve fitting program. The C. tamala SNPs also demonstrated cytotoxic activity against human lung adenocarcinoma epithelial cell line (A540) and human breast adenocarcinoma cell line (MCF-7). The mechanism of inhibition of haloarchaea by the SNPs was investigated. The plausible mechanism proposed is the alterations and disruption of haloarchaeal membrane permeability by turbulence, inhibition of respiratory dehydrogenases and lipid peroxidation causing cellular and DNA damage resulting in cell death.

New pyrazolopyridine analogs: Synthesis, antimicrobial, antiquorum-sensing and antitumor screening.

PubMed

El-Gohary, N S; Shaaban, M I

2018-05-25

New pyrazolopyridine analogs were prepared and tested for antimicrobial efficacy toward Staphylococcus aureus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, Aspergillus fumigatus and Aspergillus flavus. Results revealed that compound 6 has prominent and broad spectrum antimicrobial activity. Compound 8 showed good antibacterial efficacy over the four tested bacterial strains. In addition, compounds 2-4 displayed interesting efficacy over S. aureus, B. cereus and P. aeruginosa as well as moderate efficacy toward E. coli, C. albicans, A. fumigatus and A. flavus. Furthermore, compounds 9 and 10 exhibited interesting efficacy over P. aeruginosa. Antiquorum-sensing efficacy of the same analogs toward Chromobacterium violaceum was also examined, whereas compounds 3, 4 and 6 displayed acceptable activity. In vitro antitumor assay of the new pyrazolopyridines toward liver (HepG2), breast (MCF-7) and cervix (Hela) cancer cells illustrated that compounds 2 and 5 have the highest antitumor activity over the three cell lines. Moreover, compound 4 exhibited interesting efficacy on all tested cell lines, whereas compound 7 showed good activity on MCF-7 cells. The most active in vitro antitumor analogs, 2, 4, 5 and 7 were assessed for in vivo antitumor efficacy on Ehrlich ascites carcinoma (EAC) cells, whereas compound 5 displayed the highest efficacy. In addition, cytotoxicity testing toward W138 and WISH normal cells revealed that all tested analogs are less cytotoxic than doxorubicin. The new analogs were evaluated for DNA-binding affinity, whereas compounds 2, 4 and 5 displayed the highest affinity. In silico studies concluded that all the new pyrazolopyridines are foreseen to have excellent oral absorption. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Production of cyathane type secondary metabolites by submerged cultures of Hericium erinaceus and evaluation of their antibacterial activity by direct bioautography.

PubMed

Shen, T; Morlock, G; Zorn, H

2015-01-01

Fungi of the phylum Basidiomycota are well-known to form a broad spectrum of biologically active secondary metabolites, especially low molecular weight compounds such as terpenoids. Hericium erinaceus produces various cyathane type diterpenoids including erinacines. However, no quantitative data and production kinetics have been reported on the biosynthesis of the erinacines C and P in submerged cultures. In the present study, the production of erinacine C was optimized, and the product formation kinetics as well as the antimicrobial activity were studied by high-performance liquid chromatography (HPLC), high-performance thin-layer chromatography (HPTLC) and direct bioautography. Oatmeal and Edamin ® K were identified to be crucial media components for an efficient production of erinacine C. The highest concentrations of erinacine C were obtained in the optimized culture medium on the 9 th culture day (approximately 260 mg L -1 ). The production of erinacine P was strongly time dependent. The maximum concentration of erinacine P of 184 mg L -1 was observed on the third culture day. Afterwards, the concentrations of erinacine P decreased while the concentrations of erinacine C steadily increased. Comparable results were obtained by HPTLC with UV detection and HPLC with diode-array detection (DAD) analyses. Direct bioautography allowed for an additional analysis of the antimicrobial activity of the secondary metabolites. The C and N sources oatmeal and Edamin ® K induced the formation of erinacine C. Detailed product formation kinetics of the erinacines C and P have been reported for the first time. HPTLC combined with the Aliivibrio fischeri bioassay allowed for an instant detection of cyathane diterpenoids in crude extracts and for an evaluation of the antimicrobial activity of the secondary metabolites directly on the plate.

Effects of dietary supplementation with antimicrobial peptide-P5 on growth performance, apparent total tract digestibility, faecal and intestinal microflora and intestinal morphology of weanling pigs.

PubMed

Yoon, Jung Ho; Ingale, Santosh Laxman; Kim, Jin Soo; Kim, Kwang Hyun; Lohakare, Jayant; Park, Yoon Kyung; Park, Jun Cheol; Kwon, Ill Kyong; Chae, Byung Jo

2013-02-01

The increase in drug-resistant bacteria and the ban on antibiotic growth promoters worldwide make the search for novel means of preventing bacterial infection and promoting growth performance imperative. In this sense, antimicrobial peptides are thought to be ideal candidates owing to their antimicrobial properties, broad spectrum of activity and low propensity for development of bacterial resistance. The aim of the present study was to investigate the effect of dietary supplementation with antimicrobial peptide-P5 (AMP-P5) on weanling pig nutrition. A total of 240 weanling pigs were allotted to four treatments on the basis of initial body weight. There were four replicates in each treatment, with 15 pigs per replicate. Dietary treatments were negative control (NC, basal diet without antimicrobial), positive control (PC, basal diet + 1.5 g kg(-1) apramycin), basal diet with 40 mg kg(-1) AMP-P5 (P5-40) and basal diet with 60 mg kg(-1) AMP-P5 (P5-60). Pigs fed the PC or P5-60 diet showed improved (P < 0.05) overall growth performance, apparent total tract digestibility of dry matter, crude protein and gross energy and reduced (P < 0.05) faecal and intestinal coliforms compared with pigs fed the NC diet. The results obtained in this study indicate that dietary supplementation with 60 mg kg(-1) AMP-P5 has the potential to improve the growth performance and apparent total tract digestibility of nutrients and reduce coliforms in weanling pigs. Copyright © 2012 Society of Chemical Industry.

Single-cell, real-time detection of oxidative stress induced in Escherichia coli by the antimicrobial peptide CM15.

PubMed

Choi, Heejun; Yang, Zhilin; Weisshaar, James C

2015-01-20

Antibiotics target specific biochemical mechanisms in bacteria. In response to new drugs, pathogenic bacteria rapidly develop resistance. In contrast, antimicrobial peptides (AMPs) have retained broad spectrum antibacterial potency over millions of years. We present single-cell fluorescence assays that detect reactive oxygen species (ROS) in the Escherichia coli cytoplasm in real time. Within 30 s of permeabilization of the cytoplasmic membrane by the cationic AMP CM15 [combining residues 1-7 of cecropin A (from moth) with residues 2-9 of melittin (bee venom)], three fluorescence signals report oxidative stress in the cytoplasm, apparently involving O2 (-), H2O2, and •OH. Mechanistic studies indicate that active respiration is a prerequisite to the CM15-induced oxidative damage. In anaerobic conditions, signals from ROS are greatly diminished and the minimum inhibitory concentration increases 20-fold. Evidently the natural human AMP LL-37 also induces a burst of ROS. Oxidative stress may prove a significant bacteriostatic mechanism for a variety of cationic AMPs. If so, host organisms may use the local oxygen level to modulate AMP potency.

Dual Targeting of Intracellular Pathogenic Bacteria with a Cleavable Conjugate of Kanamycin and an Antibacterial Cell-Penetrating Peptide.

PubMed

Brezden, Anna; Mohamed, Mohamed F; Nepal, Manish; Harwood, John S; Kuriakose, Jerrin; Seleem, Mohamed N; Chmielewski, Jean

2016-08-31

Bacterial infection caused by intracellular pathogens, such as Mycobacterium, Salmonella, and Brucella, is a burgeoning global health epidemic that necessitates urgent action. However, the therapeutic value of a number of antibiotics, including aminoglycosides, against intracellular pathogenic bacteria is compromised due to their inability to traverse eukaryotic membranes. For this significant problem to be addressed, a cleavable conjugate of the antibiotic kanamycin and a nonmembrane lytic, broad-spectrum antimicrobial peptide with efficient mammalian cell penetration, P14LRR, was prepared. This approach allows kanamycin to enter mammalian cells as a conjugate linked via a tether that breaks down in the reducing environment within cells. Potent antimicrobial activity of the P14KanS conjugate was demonstrated in vitro, and this reducible conjugate effectively cleared intracellular pathogenic bacteria within macrophages more potently than that of a conjugate lacking the disulfide moiety. Notably, successful clearance of Mycobacterium tuberculosis within macrophages was observed with the dual antibiotic conjugate, and Salmonella levels were significantly reduced in an in vivo Caenorhabditis elegans model.

Efficient synthesis and evaluation of bis-pyridinium/bis-quinolinium metallosalophens as antibiotic and antitumor candidates

NASA Astrophysics Data System (ADS)

Elshaarawy, Reda F. M.; Eldeen, Ibrahim M.; Hassan, Eman M.

2017-01-01

Inspired with the pharmacological diversity of salophens and in our endeavor to explore a new strategy which may conflict the invasion of drug resistance, we report herein efficient synthetic routes for the synthesis of new RO-salophen(Cl), pyridinium/quinolinium-based salophens (3a-e) and metallosalophens (4a-j). These new architectures have been structurally characterized by elemental and spectral analysis as well pharmacologically evaluated for their in vitro antimicrobial, against a common panel of pathogenic bacterial and fungal strains, and anticancer activities against human colon carcinoma (HCT-116) cell lines. Antimicrobial assay results revealed that all tested compounds exhibited moderate to superb broad-spectrum efficacy in comparison to the standard antibiotic with a preferential ability to perform as a fungicides than to act as bactericides. Noteworthy, VO(II)-salophens are more effective in reduction HCT-116 cell viability than Cu(II)-salophens. For example, VO(II)-salophen3 (4f) (IC50 = 2.13 μg/mL) was ca. 10-fold more efficient than Cu(II)-salophen3 (4e) (IC50 = 20.30 μg/mL).

Transcriptional response of Musca domestica larvae to bacterial infection.

PubMed

Tang, Ting; Li, Xiang; Yang, Xue; Yu, Xue; Wang, Jianhui; Liu, Fengsong; Huang, Dawei

2014-01-01

The house fly Musca domestica, a cosmopolitan dipteran insect, is a significant vector for human and animal bacterial pathogens, but little is known about its immune response to these pathogens. To address this issue, we inoculated the larvae with a mixture of Escherichia coli and Staphylococcus aureus and profiled the transcriptome 6, 24, and 48 h thereafter. Many genes known to controlling innate immunity in insects were induced following infection, including genes encoding pattern recognition proteins (PGRPs), various components of the Toll and IMD signaling pathways and of the proPO-activating and redox systems, and multiple antimicrobial peptides. Interestingly, we also uncovered a large set of novel immune response genes including two broad-spectrum antimicrobial peptides (muscin and domesticin), which might have evolved to adapt to house-fly's unique ecological environments. Finally, genes mediating oxidative phosphorylation were repressed at 48 h post-infection, suggesting disruption of energy homeostasis and mitochondrial function at the late stages of infection. Collectively, our data reveal dynamic changes in gene expression following bacterial infection in the house fly, paving the way for future in-depth analysis of M. domestica's immune system.

A Dereplication and Bioguided Discovery Approach to Reveal New Compounds from a Marine-Derived Fungus Stilbella fimetaria

PubMed Central

Kildgaard, Sara; Subko, Karolina; Phillips, Emma; Goidts, Violaine; de la Cruz, Mercedes; Díaz, Caridad; Gotfredsen, Charlotte H.; Frisvad, Jens C.; Nielsen, Kristian F.; Larsen, Thomas O.

2017-01-01

A marine-derived Stilbella fimetaria fungal strain was screened for new bioactive compounds based on two different approaches: (i) bio-guided approach using cytotoxicity and antimicrobial bioassays; and (ii) dereplication based approach using liquid chromatography with both diode array detection and high resolution mass spectrometry. This led to the discovery of several bioactive compound families with different biosynthetic origins, including pimarane-type diterpenoids and hybrid polyketide-non ribosomal peptide derived compounds. Prefractionation before bioassay screening proved to be a great aid in the dereplication process, since separate fractions displaying different bioactivities allowed a quick tentative identification of known antimicrobial compounds and of potential new analogues. A new pimarane-type diterpene, myrocin F, was discovered in trace amounts and displayed cytotoxicity towards various cancer cell lines. Further media optimization led to increased production followed by the purification and bioactivity screening of several new and known pimarane-type diterpenoids. A known broad-spectrum antifungal compound, ilicicolin H, was purified along with two new analogues, hydroxyl-ilicicolin H and ilicicolin I, and their antifungal activity was evaluated. PMID:28805711

Purification and characterization of multiple bacteriocins and an inducing peptide produced by Enterococcus faecium NKR-5-3 from Thai fermented fish.

PubMed

Ishibashi, Naoki; Himeno, Kohei; Fujita, Koji; Masuda, Yoshimitsu; Perez, Rodney Honrada; Zendo, Takeshi; Wilaipun, Pongtep; Leelawatcharamas, Vichien; Nakayama, Jiro; Sonomoto, Kenji

2012-01-01

Enterocins NKR-5-3A, B, C, and D were purified from the culture supernatant of Enterococcus faecium NKR-5-3 and characterized. Among the four purified peptides, enterocin NKR-5-3A (5242.3 Da) was identical to brochocin A, produced by Brochothrix campestris ATCC 43754, in mature peptides, and its putative synergistic peptide, enterocin NKR-5-3Z, was found to be encoded in ent53Z downstream of ent53A, encoding enterocin NKR-5-3A. Enterocin NKR-5-3B (6316.4 Da) showed a broad antimicrobial spectrum, and enterocin NKR-5-3C (4512.8 Da) showed high activity against Listeria. Enterocin NKR-5-3D (2843.5 Da), showing high homology to an inducing peptide produced by Lactobacillus sakei 5, induced the production of the enterocins. The enterocins showed different antimicrobial spectra and intensities. E. faecium NKR-5-3 concomitantly produced enterocins NKR-5-3A, B, C, and D which probably belong to different classes of bacteriocins. Furthermore, NKR-5-3 production was induced by enterocin NKR-5-3D.

Antimicrobial peptides: Possible anti-infective agents.

PubMed

Lakshmaiah Narayana, Jayaram; Chen, Jyh-Yih

2015-10-01

Multidrug-resistant bacterial, fungal, viral, and parasitic infections are major health threats. The Infectious Diseases Society of America has expressed concern on the decrease of pharmaceutical companies working on antibiotic research and development. However, small companies, along with academic research institutes, are stepping forward to develop novel therapeutic methods to overcome the present healthcare situation. Among the leading alternatives to current drugs are antimicrobial peptides (AMPs), which are abundantly distributed in nature. AMPs exhibit broad-spectrum activity against a wide variety of bacteria, fungi, viruses, and parasites, and even cancerous cells. They also show potential immunomodulatory properties, and are highly responsive to infectious agents and innate immuno-stimulatory molecules. In recent years, many AMPs have undergone or are undergoing clinical development, and a few are commercially available for topical and other applications. In this review, we outline selected anion and cationic AMPs which are at various stages of development, from preliminary analysis to clinical drug development. Moreover, we also consider current production methods and delivery tools for AMPs, which must be improved for the effective use of these agents. Copyright © 2015 Elsevier Inc. All rights reserved.

Potentiation by potassium iodide using TPPS4 for antimicrobial photodynamic inactivation

NASA Astrophysics Data System (ADS)

Huang, Liyi; Hamblin, Michael R.

2018-02-01

Potassium iodide can potentiate antimicrobial photodynamic inactivation (aPDI) of a broad-spectrum of microorganisms, producing many extra logs of killing. We compared two charged porphyrins, TPPS4 (thought to be anionic and not able to bind to Gram-negative bacteria) and TMPyP4 (considered cationic and well able to bind to bacteria). As expected TPPS4 + light did not kill Gram-negative Escherichia coli, but surprisingly when 100 mM KI was added, it was highly effective at mediating aPDI (eradication at 200 nM + 10 J/cm2 of 415 nm light). TPPS4 was more effective than TMPyP4 in eradicating the Gram-positive bacteria, methicillin-resistant Staphylococcus aureus and the fungal yeast Candida albicans (regardless of KI). TPPS4 was also highly active against E. coli after a centrifugation step when KI was added, suggesting that the supposedly anionic porphyrin bound to bacteria and Candida. We conclude that TPPS4 behaves as if it has some cationic character in the presence of bacteria, which may be related to its supply from vendors in the form of a dihydrochloride salt.

Diversity and antimicrobial activity of culturable fungi from fishscale bamboo (Phyllostachys heteroclada) in China.

PubMed

Zhou, Ying-Ke; Shen, Xiao-Ye; Hou, Cheng-Lin

2017-06-01

An important and useful bamboo species, fishscale bamboo (Phyllostachys heteroclada Oliver), is broadly distributed in Southeast China and has multiple purposes, including uses in cuisine, weaving, Chinese medicine and ecological protection. However, no previous studies have focused on the endophytes of this plant. In our article, a total of 127 fungal strains were first isolated from the healthy branches and leaves of common P. heteroclada. These endophytic fungi could be directly categorized into 50 morphotypes according to their culture characteristics, and their internal transcribed spacer (ITS) regions were analyzed for molecular identification. Using the BLAST search tool of the NCBI database and phylogenetic tree analysis, these isolates were divided into two phyla, Ascomycota (95.28%) and Basidiomycota (4.72%), including at least six orders (Xylariales, Capnodiales, Pleosporales, Hypocreales, Chaetothyriales and Polyporales) and fourteen genera (Arthrinium, Pestalotiopsis, Epicoccum, Cladosporium, Nigrospora, Setophoma, Didymella, Calcarisporium, Preussia, Nemania, Creosphaeria, Ophiobolus, Phialophora and Perenniporia). It is fascinating that four genera, Calcarisporium, Preussia, Creosphaeria and Phialophora were isolated from bamboos for the first time. The inhibitory effects against clinical pathogens were also preliminarily screened, and four isolates FB43 (Calcarisporium arbuscula), FB06 (Preussia minima), FB16 (Setophoma sp.) and FB21 (Perenniporia medulla-pains) among the candidate strains displayed broad-spectrum activities according to the agar diffusion method and the disk diffusion assay. Strain FB16 (Setophoma sp.) especially indicated high bioactivity against both clinical bacteria and yeast. This study is the first report on the diversity and antimicrobial activity of the endophytic fungi associated with P. heteroclada, which could be regarded as a potential source of drug precursors and could be used in biocontrol development.

Severe soft tissue infections.

PubMed

Napolitano, Lena M

2009-09-01

Severe skin and soft tissue infections (SSTIs) frequently require management in the ICU, in part related to associated septic shock or toxic shock syndrome or associated organ failure. Four fundamental management principles are key to a successful outcome in caring for patients who have severe SSTIs, including (1) early diagnosis and differentiation of necrotizing versus nonnecrotizing SSTI, (2) early initiation of appropriate empiric broad-spectrum antimicrobial therapy with consideration of risk factors for specific pathogens and mandatory coverage for methicillin-resistant Staphylococcus aureus (MRSA), (3) source control (ie, early aggressive surgical intervention for drainage of abscesses and debridement of necrotizing soft tissue infections), and (4) pathogen identification and appropriate de-escalation of antimicrobial therapy. MRSA has emerged as the most common identifiable cause of severe SSTIs; therefore, initiation of empiric anti-MRSA antimicrobials is warranted in all cases of severe SSTIs. In addition, appropriate critical care management-including fluid resuscitation, organ support and nutritional support-is a necessary component in treating severe SSTIs.

Purification and characterization of two new cell-bound bioactive compounds produced by wild Lactococcus lactis strain.

PubMed

Saraiva, Margarete Alice Fontes; Brede, Dag Anders; Nes, Ingolf Figved; Baracat-Pereira, Maria Cristina; de Queiroz, Marisa Vieira; de Moraes, Célia Alencar

2017-07-03

Novel compounds and innovative methods are required considering that antibiotic resistance has reached a crisis point. In the study, two cell-bound antimicrobial compounds produced by Lactococcus lactis ID1.5 were isolated and partially characterized. Following purification by cationic exchange and a solid-phase C18 column, antimicrobial activity was recovered after three runs of RPC using 60% (v/v) and 100% (v/v) of 2-propanol for elution, suggesting that more than one antimicrobial compound were produced by L. lactis ID1.5, which were in this study called compounds AI and AII. The mass spectrum of AI and AII showed major intensity ions at m/z 1070.05 and 955.9 Da, respectively. The compound AI showed a spectrum of antimicrobial activity mainly against L. lactis species, while the organisms most sensitive to compound AII were Bacillus subtilis, Listeria innocua, Streptococcus pneumoniae and Pseudomonas aeruginosa. The antimicrobial activity of both compounds was suppressed by treatment with Tween 80. Nevertheless, both compounds showed high stability to heat and proteases treatments. The isolated compounds, AI and AII, showed distinct properties from other antimicrobial substances already reported as produced by L. lactis, and have a significant inhibitory effect against two clinically important respiratory pathogens. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Signaling pathways coordinating the alkaline pH response confer resistance to the hevein-type plant antimicrobial peptide Pn-AMP1 in Saccharomyces cerevisiae.

PubMed

Kwon, Youngho; Chiang, Jennifer; Tran, Grant; Giaever, Guri; Nislow, Corey; Hahn, Bum-Soo; Kwak, Youn-Sig; Koo, Ja-Choon

2016-12-01

Genome-wide screening of Saccharomyces cerevisiae revealed that signaling pathways related to the alkaline pH stress contribute to resistance to plant antimicrobial peptide, Pn-AMP1. Plant antimicrobial peptides (AMPs) are considered to be promising candidates for controlling phytopathogens. Pn-AMP1 is a hevein-type plant AMP that shows potent and broad-spectrum antifungal activity. Genome-wide chemogenomic screening was performed using heterozygous and homozygous diploid deletion pools of Saccharomyces cerevisiae as a chemogenetic model system to identify genes whose deletion conferred enhanced sensitivity to Pn-AMP1. This assay identified 44 deletion strains with fitness defects in the presence of Pn-AMP1. Strong fitness defects were observed in strains with deletions of genes encoding components of several pathways and complex known to participate in the adaptive response to alkaline pH stress, including the cell wall integrity (CWI), calcineurin/Crz1, Rim101, SNF1 pathways and endosomal sorting complex required for transport (ESCRT complex). Gene ontology (GO) enrichment analysis of these genes revealed that the most highly overrepresented GO term was "cellular response to alkaline pH". We found that 32 of the 44 deletion strains tested (72 %) showed significant growth defects compared with their wild type at alkaline pH. Furthermore, 9 deletion strains (20 %) exhibited enhanced sensitivity to Pn-AMP1 at ambient pH compared to acidic pH. Although several hundred plant AMPs have been reported, their modes of action remain largely uncharacterized. This study demonstrates that the signaling pathways that coordinate the adaptive response to alkaline pH also confer resistance to a hevein-type plant AMP in S. cerevisiae. Our findings have broad implications for the design of novel and potent antifungal agents.

A Diverse Family of Host-Defense Peptides (Piscidins) Exhibit Specialized Anti-Bacterial and Anti-Protozoal Activities in Fishes.

PubMed

Salger, Scott A; Cassady, Katherine R; Reading, Benjamin J; Noga, Edward J

2016-01-01

Conventional antibiotics and other chemical-based drugs are currently one of the most common methods used to control disease-related mortality in animal agriculture. Use of the innate immune system to decrease disease related mortalities is a novel alternative to conventional drugs. One component of the innate immune system is the host-defense peptides, also known as antimicrobial peptides. Host-defense peptides are typically small, amphipathic, α-helical peptides with a broad-spectrum of action against viral, bacterial, fungal, and/or protozoal pathogens. Piscidins are host-defense peptides first discovered in the hybrid striped bass (white bass, Morone chrysops, x striped bass, M. saxatilis). In this paper we identify four new piscidin isoforms in the hybrid striped bass and describe their tissue distributions. We also determine the progenitor species of origin of each piscidin (orthology) and propose a revised nomenclature for this newly described piscidin family based on a three class system. The Class I piscidins (22 amino acids in length; striped bass and white bass piscidin 1 and piscidin 3) show broad-spectrum activity against bacteria and ciliated protozoans, while the Class III piscidins (55 amino acids in length; striped bass and white bass piscidin 6 and striped bass piscidin 7) primarily show anti-protozoal activity. The Class II piscidins (44-46 amino acids in length; striped bass and white bass piscidin 4 and white bass piscidin 5) have a level of activity against bacteria and protozoans intermediate to Classes I and III. Knowledge of piscidin function and activity may help in the future development of disease-resistant lines of striped bass and white bass that could be used to produce superior hybrids for aquaculture.

Defining the Mode of Action of Tetramic Acid Antibacterials Derived from Pseudomonas aeruginosa Quorum Sensing Signals

PubMed Central

Lowery, Colin A.; Park, Junguk; Gloeckner, Christian; Meijler, Michael M.; Mueller, Ryan S.; Boshoff, Helena I.; Ulrich, Ricky L.; Barry, Clifton E.; Bartlett, Douglas H.; Kravchenko, Vladimir V.; Kaufmann, Gunnar F.; Janda, Kim D.

2009-01-01

In Nature, bacteria rarely exist as single, isolated entities, but rather as communities comprised of many other species including higher host organisms. To survive in these competitive environments, microorganisms have developed elaborate tactics such as the formation of biofilms and the production of antimicrobial toxins. Recently, it was discovered that the Gram-negative bacterium Pseudomonas aeruginosa, an opportunistic human pathogen, produces an antibiotic, 3-(1-hydroxydecylidene)-5-(2-hydroxyethyl)pyrrolidine-2,4-dione (C12-TA), derived from one of its quorum sensing molecules. Here, we present a comprehensive study of the expanded spectrum of C12-TA antibacterial activity against microbial competitors encountered by P. aeruginosa in Nature as well as significant human pathogens. The mechanism of action of C12-TA was also elucidated and C12-TA was found to dissipate both the membrane potential and pH gradient of Gram-positive bacteria, correlating well with cell death. Notably, in stark contrast to its parent molecule 3-oxo-dodecanoyl homoserine lactone (3-oxo-C12-HSL), neither activation of cellular stress pathways nor cytotoxicity was observed in human cells treated with C12-TA. Our results suggest that the QS machinery of P. aeruginosa has evolved for a dual-function, both to signal others of the same species, and also to defend against both host immunity and competing bacteria. Because of the broad-spectrum antibacterial activity, established mode of action, lack of rapid resistance development, and tolerance by human cells, the C12-TA scaffold may also serve as a new lead compound for the development of antimicrobial therapeutics. PMID:19807189

Effect of antibiotic order form guiding rational use of expensive drugs on cost containment.

PubMed

Sirinavin, S; Suvanakoot, P; Sathapatayavongs, B; Malatham, K

1998-09-01

New injectable antimicrobial agents are generally costly and broad-spectrum. Overusage results in unnecessary economic loss and multi-drug resistant organisms. Effective strategies for decreasing costs without compromising patient care are required. This study aimed to evaluate the economic impact of a system using an antimicrobial order form to assist rational usage of expensive antimicrobial agents. The study was performed during 1988-1996 at a 900-bed, tertiary-care, medical school hospital in Bangkok. The target drugs were 3 costly, broad-spectrum antibacterial drugs, namely imipenem, vancomycin, and injectable ciprofloxacin. The restriction of these 3 drugs was started in 1992 and was extended to netilmicin and ceftazidime in 1995. A filled antimicrobial order form (AOF) was required by pharmacists before dispensing the drugs. The AOF guided the physicians to give explicit information about anatomic diagnosis, etiologic diagnosis, and suspected antimicrobial resistance patterns of the organisms. It also contained information about indications of the restricted drugs. The filled forms were audited daily during working days by the chairman of The Hospital Antibiotic Committee. Feedback was given to the prescribers by infectious disease specialists at least twice a week. The strategy was endorsed by the executive committee of the hospital. Impact of AOF without endorsement, audit and feedback, was evaluated in 1996. The expenditures of the drugs were adjusted to the average admitted patient-days per fiscal year of the study period. The system with endorsement was well accepted and could be maintained for 4 years. The adjusted expenditures per year of the 3 restricted antibiotics were 1.41-1.87 million baht less (22-29%) in 1992-1994 than the pre-intervention year 1991. The cost reduction of imipenem and injectable ciprofloxacin could also be maintained for 1995 but not vancomycin for which use increased. The costs of these 3 restricted drugs increased very sharply (69%) in 1996 when there was loss of endorsement and capacity to perform auditing and feed back by infectious disease specialists. The system did not work with ceftazidime which was commonly used for febrile neutropenia and nosocomial infections.

Ancient Antimicrobial Peptides Kill Antibiotic-Resistant Pathogens: Australian Mammals Provide New Options

PubMed Central

Wang, Jianghui; Wong, Emily S. W.; Whitley, Jane C.; Li, Jian; Stringer, Jessica M.; Short, Kirsty R.; Renfree, Marilyn B.

2011-01-01

Background To overcome the increasing resistance of pathogens to existing antibiotics the 10×'20 Initiative declared the urgent need for a global commitment to develop 10 new antimicrobial drugs by the year 2020. Naturally occurring animal antibiotics are an obvious place to start. The recently sequenced genomes of mammals that are divergent from human and mouse, including the tammar wallaby and the platypus, provide an opportunity to discover novel antimicrobials. Marsupials and monotremes are ideal potential sources of new antimicrobials because they give birth to underdeveloped immunologically naïve young that develop outside the sterile confines of a uterus in harsh pathogen-laden environments. While their adaptive immune system develops innate immune factors produced either by the mother or by the young must play a key role in protecting the immune-compromised young. In this study we focus on the cathelicidins, a key family of antimicrobial peptide genes. Principal Finding We identified 14 cathelicidin genes in the tammar wallaby genome and 8 in the platypus genome. The tammar genes were expressed in the mammary gland during early lactation before the adaptive immune system of the young develops, as well as in the skin of the pouch young. Both platypus and tammar peptides were effective in killing a broad range of bacterial pathogens. One potent peptide, expressed in the early stages of tammar lactation, effectively killed multidrug-resistant clinical isolates of Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. Conclusions and Significance Marsupial and monotreme young are protected by antimicrobial peptides that are potent, broad spectrum and salt resistant. The genomes of our distant relatives may hold the key for the development of novel drugs to combat multidrug-resistant pathogens. PMID:21912615

In silico exploration of Red Sea Bacillus genomes for natural product biosynthetic gene clusters.

PubMed

Othoum, Ghofran; Bougouffa, Salim; Razali, Rozaimi; Bokhari, Ameerah; Alamoudi, Soha; Antunes, André; Gao, Xin; Hoehndorf, Robert; Arold, Stefan T; Gojobori, Takashi; Hirt, Heribert; Mijakovic, Ivan; Bajic, Vladimir B; Lafi, Feras F; Essack, Magbubah

2018-05-22

The increasing spectrum of multidrug-resistant bacteria is a major global public health concern, necessitating discovery of novel antimicrobial agents. Here, members of the genus Bacillus are investigated as a potentially attractive source of novel antibiotics due to their broad spectrum of antimicrobial activities. We specifically focus on a computational analysis of the distinctive biosynthetic potential of Bacillus paralicheniformis strains isolated from the Red Sea, an ecosystem exposed to adverse, highly saline and hot conditions. We report the complete circular and annotated genomes of two Red Sea strains, B. paralicheniformis Bac48 isolated from mangrove mud and B. paralicheniformis Bac84 isolated from microbial mat collected from Rabigh Harbor Lagoon in Saudi Arabia. Comparing the genomes of B. paralicheniformis Bac48 and B. paralicheniformis Bac84 with nine publicly available complete genomes of B. licheniformis and three genomes of B. paralicheniformis, revealed that all of the B. paralicheniformis strains in this study are more enriched in nonribosomal peptides (NRPs). We further report the first computationally identified trans-acyltransferase (trans-AT) nonribosomal peptide synthetase/polyketide synthase (PKS/ NRPS) cluster in strains of this species. B. paralicheniformis species have more genes associated with biosynthesis of antimicrobial bioactive compounds than other previously characterized species of B. licheniformis, which suggests that these species are better potential sources for novel antibiotics. Moreover, the genome of the Red Sea strain B. paralicheniformis Bac48 is more enriched in modular PKS genes compared to B. licheniformis strains and other B. paralicheniformis strains. This may be linked to adaptations that strains surviving in the Red Sea underwent to survive in the relatively hot and saline ecosystems.

Antimicrobial peptides effectively kill a broad spectrum of Listeria monocytogenes and Staphylococcus aureus strains independently of origin, sub-type, or virulence factor expression.

PubMed

Gottlieb, Caroline Trebbien; Thomsen, Line Elnif; Ingmer, Hanne; Mygind, Per Holse; Kristensen, Hans-Henrik; Gram, Lone

2008-11-26

Host defense peptides (HDPs), or antimicrobial peptides (AMPs), are important components of the innate immune system that bacterial pathogens must overcome to establish an infection and HDPs have been suggested as novel antimicrobial therapeutics in treatment of infectious diseases. Hence it is important to determine the natural variation in susceptibility to HDPs to ensure a successful use in clinical treatment regimes. Strains of two human bacterial pathogens, Listeria monocytogenes and Staphylococcus aureus, were selected to cover a wide range of origin, sub-type, and phenotypic behavior. Strains within each species were equally sensitive to HDPs and oxidative stress representing important components of the innate immune defense system. Four non-human peptides (protamine, plectasin, novicidin, and novispirin G10) were similar in activity profile (MIC value spectrum) to the human beta-defensin 3 (HBD-3). All strains were inhibited by concentrations of hydrogen peroxide between 0.1% - 1.0%. Sub-selections of both species differed in expression of several virulence-related factors and in their ability to survive in human whole blood and kill the nematode virulence model Caenorhabditis elegans. For L. monocytogenes, proliferation in whole blood was paralleled by high invasion in Caco-2 cells and fast killing of C. elegans, however, no such pattern in phenotypic behavior was observed for S. aureus and none of the phenotypic differences were correlated to sensitivity to HDPs. Strains of L. monocytogenes and S. aureus were within each species equally sensitive to a range of HDPs despite variations in subtype, origin, and phenotypic behavior. Our results suggest that therapeutic use of HDPs will not be hampered by occurrence of naturally tolerant strains of the two species investigated in the present study.

Detection of ctx-M gene in ESBL-producing E. coli strains isolated from urinary tract infection in Semnan, Iran.

PubMed

Tabar, Mahbobeh Mohammad; Mirkalantari, Shiva; Amoli, Rabeeh Izadi

2016-07-01

The incidence of urinary tract infections caused by Extended-Spectrum Beta Lactamase (ESBL) producing Escherichia coli (E. coli) strains due to long term and overuse of broad-spectrum cephalosporine is on the rise. CTX beta-lactamase type, a broad-spectrum beta-lactamase, has been expanding in many countries. The ctx gene is harbored on a plasmid that is spread between Enterobacteriaceae family, especially in E. coli. The aim of this study was to determine the pattern of antimicrobial resistance and investigate the prevalent ESBL phenotype and the ctx-M gene in E. coli isolated from patients with urinary tract infections (UTI) in Semnan. A cross sectional study was performed on 109 strains of E. coli isolated from the urine culture of patient suffering from a UTI referred to Shafa hospital (Semnan, Iran) during March-July 2015. Antimicrobial susceptibility testing was applied and the prevalence of the ESBL phenotype was confirmed using combination disk. PCR methods were completed for amplification of the bla ctx gene. Data were analyzed using SPSS version 18 software. One hundred ninety samples (4.16%) were identified as E. coli. Twenty one (26.6%) of E. coli were ESBL positive and 73.4% were ESBL negative. There was 100% susceptibility to imipeneme. Twenty (68.97%) out of 29 isolates were positive for the ctx-M gene, as detected by PCR. In urinary tract infections, antibiotic treatment was experimental and detailed information regarding the sensitivity of bacteria in the area can be useful to achieve the best treatment.

Structure, synthesis, and activity of dermaseptin b, a novel vertebrate defensive peptide from frog skin: relationship with adenoregulin.

PubMed

Mor, A; Amiche, M; Nicolas, P

1994-05-31

A novel antimicrobial peptide, designated dermaseptin b, was isolated from the skin of the arboreal frog Phyllomedusa bicolor. This 27-residue peptide amide is basic, containing 3 lysine residues that punctuate an alternating hydrophobic and hydrophilic sequence. In helix-inducing solvent, dermaseptin b adopts an amphipathic alpha-helical conformation that most closely resembles class L amphipathic helixes, with all lysine residues on the polar face of the helix. The peptide exhibits growth inhibition activity in vitro against a broad spectrum of pathogenic microorganisms including yeast and bacteria as well as various filamentous fungi that are responsible for severe opportunistic infections accompanying acquired immunodeficiency syndrome and the use of immunosuppressive agents. Maximized pairwise sequence alignment of dermaseptin b and dermaseptin s, a 34-residue antimicrobial peptide previously isolated from Phyllomedusa sauvagii, reveals 81% amino acid identity. No other significant similarity was found between dermaseptin b and any prokaryotic or eukaryotic protein, but similarity was found with adenoregulin (38% amino acid postional identity), a 33-residue peptide that enhances binding of agonists to the A1 adenosine receptor. The synthetic replicates of dermaseptin b and adenoregulin displayed similar but nonidentical spectra of antimicrobial activity, and both peptides were devoid of lytic effect on mammalian cells. Accordingly, the observation that adenoregulin enhances binding of agonists to the adenosine receptor may in fact be a consequence of its ability to alter the structure of biological membranes and to produce signal transduction via interactions with the lipid bilayer, bypassing cell surface receptor interactions.

Preparation methods for monodispersed garlic oil microspheres in water using the microemulsion technique and their potential as antimicrobials.

PubMed

Zheng, Hua Ming; Li, Hou Bin; Wang, Da Wei; Liu, Dun

2013-08-01

Garlic oil is considered as a natural broad-spectrum antibiotic because of its well-known antimicrobial activity. However, the characteristics of easy volatility and poor aqueous solubility limit the application of garlic oil in industry. The purpose of the present work is to develop and evaluate an oil-free microemulsion by loading garlic oil in microemulsion system. Microemulsions were prepared with ethoxylated hydrogenated castor (Cremophor RH40) as surfactant, n-butanol (or ethanol) as cosurfactant, oleic acid-containing garlic oil as oil phase, and ultrapure water as water phase. The effects of the ratio of surfactant to cosurfactant and different oil concentration on the area of oil-in-water (O/W) microemulsion region in pseudoternary phase diagrams were investigated. The particle size and garlic oil encapsulation efficiency of the formed microemulsions with different formulations were also investigated. In addition, the antimicrobial activity in vitro against Escherichia coli and Staphylococcus aureus was assessed. The experimental results show that a stable microemulsion region can be obtained when the mass ratio of surfactant to cosurfactant is, respectively, 1:1, 2:1, and 3:1. Especially, when the mixture surfactants of RH40/n-butanol 2/1 (w/w) is used in the microemulsion formulation, the area of O/W microemulsion region is 0.089 with the particle size 13.29 to 13.85 nm and garlic oil encapsulation efficiency 99.5%. The prepared microemulsion solution exhibits remarkable antibacterial activity against S. aureus. © 2013 Institute of Food Technologists®

Reprogrammable microbial cell-based therapeutics against antibiotic-resistant bacteria.

PubMed

Hwang, In Young; Koh, Elvin; Kim, Hye Rim; Yew, Wen Shan; Chang, Matthew Wook

2016-07-01

The discovery of antimicrobial drugs and their subsequent use has offered an effective treatment option for bacterial infections, reducing morbidity and mortality over the past 60 years. However, the indiscriminate use of antimicrobials in the clinical, community and agricultural settings has resulted in selection for multidrug-resistant bacteria, which has led to the prediction of possible re-entrance to the pre-antibiotic era. The situation is further exacerbated by significantly reduced antimicrobial drug discovery efforts by large pharmaceutical companies, resulting in a steady decline in the number of new antimicrobial agents brought to the market in the past several decades. Consequently, there is a pressing need for new antimicrobial therapies that can be readily designed and implemented. Recently, it has become clear that the administration of broad-spectrum antibiotics can lead to collateral damage to the human commensal microbiota, which plays several key roles in host health. Advances in genetic engineering have opened the possibility of reprogramming commensal bacteria that are in symbiotic existence throughout the human body to implement antimicrobial drugs with high versatility and efficacy against pathogenic bacteria. In this review, we discuss recent advances and potentialities of engineered bacteria in providing a novel antimicrobial strategy against antibiotic resistance. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antimicrobial Stewardship in a Community Hospital: Attacking the More Difficult Problems

PubMed Central

Philmon, Carla L.; Johnson, Gregory D.; Ward, William S.; Rivers, LaToya L.; Williamson, Sharon A.; Goodman, Edward L.

2014-01-01

Background: Antibiotic stewardship has been proposed as an important way to reduce or prevent antibiotic resistance. In 2001, a community hospital implemented an antimicrobial management program. It was successful in reducing antimicrobial utilization and expenditure. In 2011, with the implementation of a data-mining tool, the program was expanded and its focus transitioned from control of antimicrobial use to guiding judicious antimicrobial prescribing. Objective: To test the hypothesis that adding a data-mining tool to an existing antimicrobial stewardship program will further increase appropriate use of antimicrobials. Design: Interventional study with historical comparison. Methods: Rules and alerts were built into the data-mining tool to aid in identifying inappropriate antibiotic utilization. Decentralized pharmacists acted on alerts for intravenous (IV) to oral conversion, perioperative antibiotic duration, and restricted antimicrobials. An Infectious Diseases (ID) Pharmacist and ID Physician/Hospital Epidemiologist focused on all other identified alert types such as antibiotic de-escalation, bug-drug mismatch, and double coverage. Electronic chart notes and phone calls to physicians were utilized to make recommendations. Results: During 2012, 2,003 antimicrobial interventions were made with a 90% acceptance rate. Targeted broad-spectrum antimicrobial use decreased by 15% in 2012 compared to 2010, which represented cost savings of $1,621,730. There were no statistically significant changes in antimicrobial resistance, and no adverse patient outcomes were noted. Conclusions: The addition of a data-mining tool to an antimicrobial stewardship program can further decrease inappropriate use of antimicrobials, provide a greater reduction in overall antimicrobial use, and provide increased cost savings without negatively affecting patient outcomes. PMID:25477615

Dual-Functional Polyethylene Glycol-b-polyhexanide Surface Coating with in Vitro and in Vivo Antimicrobial and Antifouling Activities.

PubMed

Zhi, Zelun; Su, Yajuan; Xi, Yuewei; Tian, Liang; Xu, Miao; Wang, Qianqian; Padidan, Sara; Li, Peng; Huang, Wei

2017-03-29

In recent years, microbial colonization on the surface of biomedical implants/devices has become a severe threat to human health. Herein, surface-immobilized guanidine derivative block copolymers create an antimicrobial and antifouling dual-functional coating. We report the preparation of an antimicrobial and antifouling block copolymer by the conjugation of polyhexanide (PHMB) with either allyl glycidyl ether or allyloxy polyethylene glycol (APEG; MW 1200 and 2400). The allyl glycidyl ether modified PHMB (A-PHMB) and allyloxy polyethylene glycol 1200/2400 modified PHMB (APEG 1200/2400 -PHMB) copolymers were grafted onto a silicone rubber surface as a bottlebrush-like coating, respectively, using a plasma-UV-assisted surface-initiated polymerization. Both A-PHMB and APEG 1200/2400 -PHMB coatings exhibited excellent broad-spectrum antimicrobial properties against Gram-negative/positive bacteria and fungi. The APEG 2400 -PHMB coating displayed an improved antibiofilm as well as antifouling properties and a long reusable cycle, compared with two other coatings, due to its abundant PEG blocks among those copolymers. Also, the APEG 2400 -PHMB-coated silicone coupons were biocompatible toward mammalian cells, as revealed by in vitro hemocompatibile and cytotoxic assays. An in vivo study showed a significant decline of Escherichia coli colonies with a 5-log reduction, indicating the APEG 2400 -PHMB coating surface worked effectively in the rodent subcutaneous infection model. This PHMB-based block copolymer coating is believed to be an effective strategy to prevent biomaterial-associated infections.

Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping

PubMed Central

Nicolau, Carolina Alves; Prorock, Alyson; Bao, Yongde; Neves-Ferreira, Ana Gisele da Costa; Fox, Jay William

2018-01-01

Snake venoms are sources of molecules with proven and potential therapeutic applications. However, most activities assayed in venoms (or their components) are of hemorrhagic, hypotensive, edematogenic, neurotoxic or myotoxic natures. Thus, other relevant activities might remain unknown. Using functional genomics coupled to the connectivity map (C-map) approach, we undertook a wide range indirect search for biological activities within the venom of the South American pit viper Bothrops jararaca. For that effect, venom was incubated with human breast adenocarcinoma cell line (MCF7) followed by RNA extraction and gene expression analysis. A list of 90 differentially expressed genes was submitted to biosimilar drug discovery based on pattern recognition. Among the 100 highest-ranked positively correlated drugs, only the antihypertensive, antimicrobial (both antibiotic and antiparasitic), and antitumor classes had been previously reported for B. jararaca venom. The majority of drug classes identified were related to (1) antimicrobial activity; (2) treatment of neuropsychiatric illnesses (Parkinson’s disease, schizophrenia, depression, and epilepsy); (3) treatment of cardiovascular diseases, and (4) anti-inflammatory action. The C-map results also indicated that B. jararaca venom may have components that target G-protein-coupled receptors (muscarinic, serotonergic, histaminergic, dopaminergic, GABA, and adrenergic) and ion channels. Although validation experiments are still necessary, the C-map correlation to drugs with activities previously linked to snake venoms supports the efficacy of this strategy as a broad-spectrum approach for biological activity screening, and rekindles the snake venom-based search for new therapeutic agents. PMID:29415440

Biocompatibility of antimicrobial melimine lenses: rabbit and human studies.

PubMed

Dutta, Debarun; Ozkan, Jerome; Willcox, Mark D P

2014-05-01

Covalent immobilization of antimicrobial peptide melimine onto contact lenses can produce broad-spectrum antimicrobial lenses. The purpose of this study was to investigate the performance of melimine-coated contact lenses in an animal model and human clinical trial. Melimine was covalently attached onto the surface of contact lenses via EDC (1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride) coupling. A rabbit model of daily contralateral wear of lenses for 22 days was conducted to assess the lens safety. A prospective, randomized, double-masked, one-day human clinical trial was used to evaluate subjective responses and ocular physiology during contralateral wear of melimine-coated (test) and uncoated (control) lenses. Delayed reactions were monitored during follow-up visits after 1 and 4 weeks. Ex vivo retention of antimicrobial activity of worn lenses was assessed by reduction in numbers of viable Pseudomonas aeruginosa and Staphylococcus aureus. Melimine-coated lenses produced no ocular signs or symptoms that would indicate cytotoxicity during the lens wear of rabbits. No histological changes were found in rabbit corneas. During the human trial, no differences were observed in wettability, surface deposition, lens-fitting centration, movement, tightness, and corneal coverage between test and control lenses (p > 0.05). There were no significant differences in bulbar, limbal, or palpebral redness or conjunctival staining (p > 0.05). Mean corneal (extent, depth, and type) staining was higher for test lenses compared with that for control lenses (p < 0.05). There was no significant difference in subjective responses for lens comfort, dryness, and awareness (p > 0.05). No delayed reactions were associated with the test lenses. Worn test lenses retained more than 1.5 log inhibition against both bacterial types. Melimine-coated contact lenses were worn safely by humans. However, they were associated with higher corneal staining. The melimine-coated lenses retained high antibacterial activity after wear.

Sonorensin: an Antimicrobial Peptide, Belonging to the Heterocycloanthracin Subfamily of Bacteriocins, from a New Marine Isolate, Bacillus sonorensis MT93

PubMed Central

Chopra, Lipsy; Singh, Gurdeep; Choudhary, Vikas

2014-01-01

Marine environments are the greatest fronts of biodiversity, representing a resource of unexploited or unknown microorganisms and new substances having potential applications. Among microbial products, antimicrobial peptides (AMPs) have received great attention recently due to their applications as food preservatives and therapeutic agents. A new marine soil isolate producing an AMP was identified as Bacillus sonorensis based on 16S rRNA gene sequence analysis. It produced an AMP that showed a broad spectrum of activity against both Gram-positive and Gram-negative bacteria. The peptide, named sonorensin, was purified to homogeneity using a combination of chromatographic techniques. The intact molecular mass of the purified peptide, 6,274 Da, as revealed by matrix-assisted laser desorption ionization–time of flight (MALDI-TOF), was in agreement with Tricine-SDS-PAGE analysis. A PCR array of primers was used to identify AMP structural genes, which allowed the successful amplification of the related genes from strain MT93. The putative open reading frame of sonorensin was amplified, cloned into the pET-32a(+) vector, expressed as a thioredoxin (Trx) fusion protein in Escherichia coli, and then purified. Sequence alignment analysis revealed that the bacteriocin being reported could belong to new subfamily of bacteriocins, heterocycloanthracin. The peptide indicated its potential as a biocontrol agent or food antimicrobial agent, due to its antimicrobial activity against bacteria such as Listeria monocytogenes and Staphylococcus aureus. This is the first report of the production, purification, and characterization of wild-type and recombinant bacteriocin by B. sonorensis and the first bacteriocin of the heterocycloanthracin subfamily to be characterized. PMID:24610839

Sonorensin: an antimicrobial peptide, belonging to the heterocycloanthracin subfamily of bacteriocins, from a new marine isolate, Bacillus sonorensis MT93.

PubMed

Chopra, Lipsy; Singh, Gurdeep; Choudhary, Vikas; Sahoo, Debendra K

2014-05-01

Marine environments are the greatest fronts of biodiversity, representing a resource of unexploited or unknown microorganisms and new substances having potential applications. Among microbial products, antimicrobial peptides (AMPs) have received great attention recently due to their applications as food preservatives and therapeutic agents. A new marine soil isolate producing an AMP was identified as Bacillus sonorensis based on 16S rRNA gene sequence analysis. It produced an AMP that showed a broad spectrum of activity against both Gram-positive and Gram-negative bacteria. The peptide, named sonorensin, was purified to homogeneity using a combination of chromatographic techniques. The intact molecular mass of the purified peptide, 6,274 Da, as revealed by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF), was in agreement with Tricine-SDS-PAGE analysis. A PCR array of primers was used to identify AMP structural genes, which allowed the successful amplification of the related genes from strain MT93. The putative open reading frame of sonorensin was amplified, cloned into the pET-32a(+) vector, expressed as a thioredoxin (Trx) fusion protein in Escherichia coli, and then purified. Sequence alignment analysis revealed that the bacteriocin being reported could belong to new subfamily of bacteriocins, heterocycloanthracin. The peptide indicated its potential as a biocontrol agent or food antimicrobial agent, due to its antimicrobial activity against bacteria such as Listeria monocytogenes and Staphylococcus aureus. This is the first report of the production, purification, and characterization of wild-type and recombinant bacteriocin by B. sonorensis and the first bacteriocin of the heterocycloanthracin subfamily to be characterized.

In Vivo Effects of Pichia Pastoris-Expressed Antimicrobial Peptide Hepcidin on the Community Composition and Metabolism Gut Microbiota of Rats.

PubMed

Tian, Lanfang; Chen, Siyuan; Liu, Haiyan; Guo, Mingzhang; Xu, Wentao; He, Xiaoyun; Luo, Yunbo; Qi, Xiaozhe; Luo, Hongxia; Huang, Kunlun

2016-01-01

Hepcidin, one kind of antimicrobial peptides, is one of the promising alternatives to antibiotics with broad spectrum of antimicrobial activity. Hepcidins cloned from different kinds of fishes have been produced using exogenous expression systems, and their in vitro antimicrobial effects have been verified. However their in vivo effects on gut microbiota and gut health of hosts remain unclear. Here we performed a safety study of hepcidin so that it can be used to reduce microbial contaminations in the food and feed. In this study, Pichia pastoris-expressed Pseudosciaena crocea hepcidin (PC-hepc) was first assessed by simulated digestion tests and then administered to male and female Sprague-Dawley (SD) rats in different concentrations. Subchronic toxicity testing, high throughput 16S rRNA sequencing of gut microbiota, and examinations on gut metabolism and permeability were conducted. The results showed PC-hepc could be digested in simulated intestinal fluid but not in simulated gastric fluid. PC-hepc had no adverse effects on general health, except causing increase of blood glucose (still in the normal value range of this index) in all trial groups of female rats and intestinal inflammation in HD group of female rats. Community composition of gut microbiota of female MD and HD groups shifted compared with control group, of which the decrease of genus Akkermansia might be related to the increase of blood glucose and intestinal inflammation. Significant increase of fecal nitroreductase activity was also observed in female MD and HD groups. Our results suggest the uses of exogenous PC-hepc in normal dosage are safe, however excess dosage of it may cause intestinal disorder of animals.

Antimicrobial/cytolytic peptides from the venom of the North African scorpion, Androctonus amoreuxi: biochemical and functional characterization of natural peptides and a single site-substituted analog.

PubMed

Almaaytah, Ammar; Zhou, Mei; Wang, Lei; Chen, Tianbao; Walker, Brian; Shaw, Chris

2012-06-01

The venoms of scorpions are complex cocktails of polypeptide toxins that fall into two structural categories: those that contain cysteinyl residues with associated disulfide bridges and those that do not. As the majority of lethal toxins acting upon ion channels fall into the first category, most research has been focused there. Here we report the identification and structural characterization of two novel 18-mer antimicrobial peptides from the venom of the North African scorpion, Androctonus amoreuxi. Named AamAP1 and AamAP2, both peptides are C-terminally amidated and differ in primary structure at just two sites: Leu-->Pro at position 2 and Phe-->Ile at position 17. Synthetic replicates of both peptides exhibited a broad-spectrum of antimicrobial activity against a Gram-positive bacterium (Staphylococcus aureus), a Gram-negative bacterium (Escherichia coli) and a yeast (Candida albicans), at concentrations ranging between 20 μM and 150 μM. In this concentration range, both peptides produced significant degrees of hemolysis. A synthetic replicate of AamAP1 containing a single substitution (His-->Lys) at position 8, generated a peptide (AamAP-S1) with enhanced antimicrobial potency (3-5 μM) against the three test organisms and within this concentration range, hemolytic effects were negligible. In addition, this His-->Lys variant exhibited potent growth inhibitory activity (ID(50) 25-40 μm) against several human cancer cell lines and endothelial cells that was absent in both natural peptides. Natural bioactive peptide libraries, such as those that occur in scorpion venoms, thus constitute a unique source of novel lead compounds with drug development potential whose biological properties can be readily manipulated by simple synthetic chemical means. Copyright © 2012 Elsevier Inc. All rights reserved.

Novel 3-Aminothiazolquinolones: Design, Synthesis, Bioactive Evaluation, SARs, and Preliminary Antibacterial Mechanism.

PubMed

Cui, Sheng-Feng; Addla, Dinesh; Zhou, Cheng-He

2016-05-26

A series of novel 3-aminothiazolquinolones as analogues of quinolone antibacterial agents were designed and synthesized in an effort to circumvent quinolone resistance. Among these 3-aminothiazolquinolones, 3-(2-aminothiazol-4-yl)-7-chloro-6-(pyrrolidin-1-yl) quinolone 12b exhibited potent antibacterial activity, low cytotoxicity to hepatocyte cells, strong inhibitory potency to DNA gyrase, and a broad antimicrobial spectrum including against multidrug-resistant strains. This active molecule 12b also induced bacterial resistance more slowly than norfloxacin. Analysis of structure-activity relationships (SARs) disclosed that the 2-aminothiazole fragment at the 3-position of quinolone plays an important role in exerting antibacterial activity. Molecular modeling and experimental investigation of aminothiazolquinolone 12b with DNA from a sensitive methicillin-resistant Staphylococcus aureus (MRSA) strain revealed that the possible antibacterial mechanism might be related to the formation of a compound 12b-Cu(2+)-DNA ternary complex in which the Cu(2+) ion acts as a bridge between the backbone of 3-aminothiazolquinolone and the phosphate group of the nucleic acid.

Fluorescent Trimethoprim Conjugate Probes To Assess Drug Accumulation in Wild Type and Mutant Escherichia coli

PubMed Central

2016-01-01

Reduced susceptibility to antimicrobials in Gram-negative bacteria may result from multiple resistance mechanisms, including increased efflux pump activity or reduced porin protein expression. Up-regulation of the efflux pump system is closely associated with multidrug resistance (MDR). To help investigate the role of efflux pumps on compound accumulation, a fluorescence-based assay was developed using fluorescent derivatives of trimethoprim (TMP), a broad-spectrum synthetic antibiotic that inhibits an intracellular target, dihydrofolate reductase (DHFR). Novel fluorescent TMP probes inhibited eDHFR activity with comparable potency to TMP, but did not kill or inhibit growth of wild type Escherichia coli. However, bactericidal activity was observed against an efflux pump deficient E. coli mutant strain (ΔtolC). A simple and quick fluorescence assay was developed to measure cellular accumulation of the TMP probe using either fluorescence spectroscopy or flow cytometry, with validation by LC-MS/MS. This fluorescence assay may provide a simple method to assess efflux pump activity with standard laboratory equipment. PMID:27737551

In vitro probiotic characterization of Lactobacillus strains from fermented radish and their anti-adherence activity against enteric pathogens.

PubMed

Damodharan, Karthiyaini; Palaniyandi, Sasikumar Arunachalam; Yang, Seung Hwan; Suh, Joo-Won

2015-11-01

In this study, we evaluated the probiotic properties of Lactobacillus plantarum, Lactobacillus pentosus, and Lactobacillus fermentum strains isolated from fermented radish. All the strains survived the simulated oro-gastrointestinal transit condition and showed significantly higher adherence to Caco-2 cells compared with the probiotic strain Lactobacillus rhamnosus GG. The strains showed broad-spectrum antimicrobial activity, autoaggregation, and coaggregation capacity with pathogens. Furthermore, the Lactobacillus strains inhibited the adherence of Yersinia enterocolitica subsp. enterocolitica, Shigella boydii, and Salmonella choleraesuis to the Caco-2 cell line. The strains possessed bile salt hydrolase activity and their cholesterol-lowering activity in vitro was above 50% in the presence of bile. Strains of L. plantarum and L. pentosus possessed the plantaricin-encoding plnEF gene. In addition, the Lactobacillus strains maintained about 80% cell viability after freeze-drying in the presence of a combination of 5% skim milk and 5% maltodextrin as cryoprotectant, and 70% recovery of cell viability was observed in the absence of any cryoprotectant.

Declines in Outpatient Antimicrobial Use in Canada (1995–2010)

PubMed Central

Finley, Rita; Glass-Kaastra, Shiona K.; Hutchinson, Jim; Patrick, David M.; Weiss, Karl; Conly, John

2013-01-01

Background With rising reports of antimicrobial resistance in outpatient communities, surveillance of antimicrobial use is imperative for supporting stewardship programs. The primary objective of this article is to assess the levels of antimicrobial use in Canada over time. Methods Canadian antimicrobial use data from 1995 to 2010 were acquired and assessed by four metrics: population-adjusted prescriptions, Defined Daily Doses, spending on antimicrobials (inflation-adjusted), and average Defined Daily Doses per prescription. Linear mixed models were built to assess significant differences among years and antimicrobial groups, and to account for repeated measurements over time. Measures were also compared to published reports from European countries. Results Temporal trends in antimicrobial use in Canada vary by metric and antimicrobial grouping. Overall reductions were seen for inflation-adjusted spending, population-adjusted prescription rates and Defined Daily Doses, and increases were observed for the average number of Defined Daily Doses per prescription. The population-adjusted prescription and Defined Daily Doses values for 2009 were comparable to those reported by many European countries, while the average Defined Daily Dose per prescription for Canada ranked high. A significant reduction in the use of broad spectrum penicillins occurred between 1995 and 2004, coupled with increases in macrolide and quinolone use, suggesting that replacement of antimicrobial drugs may occur as new products arrive on the market. Conclusions There have been modest decreases of antimicrobial use in Canada over the past 15 years. However, continued surveillance of antimicrobial use coupled with data detailing antimicrobial resistance within bacterial pathogens affecting human populations is critical for targeting interventions and maintaining the effectiveness of these products for future generations. PMID:24146863

Cloning and sequencing of Staphylococcus aureus murC, a gene essential for cell wall biosynthesis.

PubMed

Lowe, A M; Deresiewicz, R L

1999-01-01

Staphylococcus aureus is a major human pathogen that is increasingly resistant to clinically useful antimicrobial agents. While screening for S. aureus genes expressed during mammalian infection, we isolated murC. This gene encodes UDP-N-acetylmuramoyl-L-alanine synthetase, an enzyme essential for cell wall biosynthesis in a number of bacteria. S. aureus MurC has a predicted mass 49,182 Da and complements the temperature-sensitive murC mutation of E. coli ST222. Sequence data on the DNA flanking staphylococcal murC suggests that the local gene organization there parallels that found in B. subtilis, but differs from that found in gram-negative bacterial pathogens. MurC proteins represent promising targets for broad spectrum antimicrobial drug development.

The novel antimicrobial peptides from skin of Chinese broad-folded frog, Hylarana latouchii (Anura:Ranidae).

PubMed

Wang, Hui; Lu, Yi; Zhang, Xiuqing; Hu, Yuhong; Yu, Haining; Liu, Jingze; Sun, Junshe

2009-02-01

Broad-folded frogs (Hylarana latouchii), one member of 12 species of the genus Hylarana in the Chinese frog fauna, are widely distributed in the South of China. In this study, we purified and characterized three antimicrobial peptides from the skin secretion of H. latouchii. Five different cDNA fragments encoding the precursors of these antimicrobial peptides were cloned, and five mature antimicrobial peptides belonging to two different families were deduced from the five cDNAs. Structural characterization of the mature peptides had identified them as members of the brevinin-1 and temporin families. They were named brevinin-1LTa (FFGTALKIAANVLPTAICKILKKC), brevinin-1LTb (FFGTALKIAANILPTAICKILKKC), temporin-LTa (FFPLVLGALGSILPKIF-NH(2)), temporin-LTb (FIITGLVRGLTKLF-NH(2)) and temorin-LTc (SLSRFLSFLKIVYPPAF-NH(2)). Brevinin-1LTa, temporin-LTa, temporin-LTb and temporin-LTc with different antimicrobial activities induced significant morphological alterations of the tested microbial surfaces as shown by scanning electron microscopy, which indicated strong membrane disruption.

Antimicrobial activity of Nigerian medicinal plants

PubMed Central

Anyanwu, Madubuike Umunna; Okoye, Rosemary Chinazam

2017-01-01

Antimicrobial resistance (AMR) is currently one of the major threats facing mankind. The emergence and rapid spread of multi- and pan-drug-resistant organisms (such as vancomycin-, methicillin-, extended-spectrum β-lactam-, carbapenem- and colistin-resistant organisms) has put the world in a dilemma. The health and economic burden associated with AMR on a global scale are dreadful. Available antimicrobials have been misused and are almost ineffective with some of these drugs associated with dangerous side effects in some individuals. Development of new, effective, and safe antimicrobials is one of the ways by which AMR burden can be reduced. The rate at which microorganisms develop AMR mechanisms outpaces the rate at which new antimicrobials are being developed. Medicinal plants are potential sources of new antimicrobial molecules. There is renewed interest in antimicrobial activities of phytochemicals. Nigeria boasts of a huge heritage of medicinal plants and there is avalanche of researches that have been undertaken to screen antimicrobial activities of these plants. Scientific compilation of these studies could provide useful information on the antimicrobial properties of the plants. This information can be useful in the development of new antimicrobial drugs. This paper reviews antimicrobial researches that have been undertaken on Nigerian medicinal plants. PMID:28512606

Review of the spectrum and potency of orally administered cephalosporins and amoxicillin/clavulanate.

PubMed

Sader, Helio S; Jacobs, Michael R; Fritsche, Thomas R

2007-03-01

The antimicrobial spectrum and in vitro potency of the most frequently prescribed orally administered cephalosporins (cefaclor, cefdinir, cefpodoxime, cefprozil, cefuroxime axetil, cephalexin) and amoxicillin/clavulanate are reviewed. These beta-lactam agents have been widely used in the outpatient arena for the treatment of community-acquired respiratory tract and other mild-to-moderate infections. The data presented here were obtained from critical review articles on each of these compounds. Cephalexin and cefaclor were among the least potent and had the narrowest antimicrobial spectrums against the pathogens evaluated. In contrast, cefdinir, cefpodoxime, cefprozil, and cefuroxime were highly active against penicillin-susceptible Streptococcus pneumoniae and retained some activity against penicillin-intermediate strains, whereas amoxicillin/clavulanate was the most active against S. pneumoniae, including most penicillin nonsusceptible strains. Amoxicillin/clavulanate and cefdinir were the most potent compounds against methicillin (oxacillin)-susceptible Staphylococcus aureus, whereas cefpodoxime was the most potent compound against Haemophilus influenzae. Amoxicillin/clavulanate, cefdinir, and cefpodoxime were also active against Moraxella catarrhalis, including beta-lactamase-producing strains. In summary, orally administered "3rd-generation" or extended spectrum cephalosporins exhibited more balanced spectrums of activity against the principal bacterial pathogens responsible for outpatient respiratory tract and other infections when compared with other widely used oral cephalosporins of earlier generations or amoxicillin alone.

Old dog begging for new tricks – Current practices and future directions in the diagnosis of delayed antimicrobial hypersensitivity

PubMed Central

Konvinse, KC; Phillips, E; White, KD; Trubiano, JA

2016-01-01

Purpose of review Antimicrobials are a leading cause of severe T-cell-mediated adverse drug reactions (ADRs). The purpose of this review is to address the current understanding of antimicrobial cross-reactivity and the ready availability of and evidence for in vitro, in vivo and ex vivo diagnostics for T-cell-mediated ADRs. Recent findings Recent literature has evaluated the efficacy of traditional antibiotic allergy management including patch testing, skin prick testing, intradermal testing and oral challenge. While patch and intradermal testing are specific for the diagnosis of immune-mediated (IM) ADRs, they suffer from drug-specific limitations in sensitivity. The use of ex vivo diagnostics, especially ELISpot has been highlighted as a promising new approach to assigning causality. Knowledge of true rates of antimicrobial cross-reactivity aids empirical antibiotic choice in the setting of previous IM-ADRs. Summary In an era of increasing antimicrobial resistance and use of broad-spectrum antimicrobial therapy, ensuring patients are assigned the correct “allergy label” is essential. Re-exposure to implicated antimicrobials, especially in the setting of severe adverse cutaneous reaction is associated with significant morbidity and mortality. The process through which an antibiotic label gets assigned, acted on and maintained is still imprecise. Predicting T-cell-mediated ADRs via personalised approaches, including HLA-typing may pave future pathways to safer antimicrobial prescribing guidelines. PMID:27753687

In vitro production and antifungal activity of peptide ABP-dHC-cecropin A.

PubMed

Zhang, Jiaxin; Movahedi, Ali; Xu, Junjie; Wang, Mengyang; Wu, Xiaolong; Xu, Chen; Yin, Tongming; Zhuge, Qiang

2015-04-10

The antimicrobial peptide ABP-dHC-cecropin A is a small cationic peptide with potent activity against a wide range of bacterial species. Evidence of antifungal activity has also been suggested; however, testing of this peptide has been limited due to the low expression of cecropin proteins in Escherichia coli. To improve expression of this peptide in E. coli, ABP-dHC-cecropin A was cloned into a pSUMO vector and transformed into E. coli, resulting in the production of a pSUMO-ABP-dHC-cecropin A fusion protein. The soluble form of this protein was then purified by Ni-IDA chromatography, yielding a total of 496-mg protein per liter of fermentation culture. The SUMO-ABP-dHC-cecropin A fusion protein was then cleaved using a SUMO protease and re-purified by Ni-IDA chromatography, yielding a total of 158-mg recombinant ABP-dHC-cecropin A per liter of fermentation culture at a purity of ≥94%, the highest yield reported to date. Antifungal activity assays performed using this purified recombinant peptide revealed strong antifungal activity against both Candida albicans and Neurospora crassa, as well as Rhizopus, Fusarium, Alternaria, and Mucor species. Combined with previous analyses demonstrating strong antibacterial activity against a number of important bacterial pathogens, these results confirm the use of ABP-dHC-cecropin A as a broad-spectrum antimicrobial peptide, with significant therapeutic potential. Copyright © 2015 Elsevier B.V. All rights reserved.

Activity of antimicrobial peptide mimetics in the oral cavity: II. Activity against periopathogenic biofilms and anti-inflammatory activity

PubMed Central

Hua, J; Scott, R.W.; Diamond, G

2011-01-01

Whereas periodontal disease is ultimately of bacterial etiology, from multispecies biofilms of gram-negative anaerobic microorganisms, much of the deleterious effects are caused by the resultant epithelial inflammatory response. Hence, development of a treatment that combines anti-biofilm antibiotic activity with anti-inflammatory activity would be of great utility. Antimicrobial peptides (AMPs) such as defensins are naturally occurring peptides that exhibit broad-spectrum activity as well as a variety of immunomodulatory activities. Furthermore, bacteria do not readily develop resistance to these agents. However, clinical studies have suggested that they do not represent optimal candidates for exogenous therapeutic agents. Small-molecule mimetics of these AMPs exhibit similar activities to the parent peptides, in addition to having low toxicity, high stability and low cost. To determine whether AMP mimetics have the potential for treatment of periodontal disease, we examined the activity of one mimetic, mPE, against biofilm cultures of Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. Metabolic assays as well as culture and biomass measurement assays demonstrated that mPE exhibits potent activity against biofilm cultures of both species. Furthermore, as little as 2 µg ml−1 mPE was sufficient to inhibit interleukin-1β-induced secretion of interleukin-8 in both gingival epithelial cells and THP-1 cells. This anti-inflammatory activity is associated with a reduction in activation of nuclear factor-κB, suggesting that mPE can act both as an anti-biofilm agent in an anaerobic environment and as an anti-inflammatory agent in infected tissues. PMID:21040516

Large-Scale Purification, Characterization, and Spore Outgrowth Inhibitory Effect of Thurincin H, a Bacteriocin Produced by Bacillus thuringiensis SF361.

PubMed

Wang, Gaoyan; Manns, David C; Guron, Giselle K; Churey, John J; Worobo, Randy W

2014-06-01

Large-scale purification of the highly hydrophobic bacteriocin thurincin H was accomplished via a novel and simple two-step method: ammonia sulfate precipitation and C18 solid-phase extraction. The inhibition spectrum and stability of thurincin H as well as its antagonistic activity against Bacillus cereus F4552 spores were further characterized. In the purification method, secreted proteins contained in the supernatant of a 40 h incubated culture of B. thuringiensis SF361 were precipitated by 68 % ammonia sulfate and purified by reverse-phase chromatography, with a yield of 18.53 mg/l of pure thurincin H. Silver-stained SDS-PAGE, high-performance liquid chromatography, and liquid chromatography-mass spectrometry confirmed the high purity of the prepared sample. Thurincin H exhibited a broad antimicrobial activity against 22 tested bacterial strains among six different genera including Bacillus, Carnobacterium, Geobacillus, Enterococcus, Listeria, and Staphylococcus. There was no detectable activity against any of the selected yeast or fungi. The bacteriocin activity was stable for 30 min at 50 °C and decreased to undetectable levels within 10 min at temperatures above 80 °C. Thurincin H is also stable from pH 2-7 for at least 24 h at room temperature. Thurincin H is germicidal against B. cereus spores in brain heart infusion broth, but not in Tris-NaCl buffer. The efficient purification method enables the large-scale production of pure thurincin H. The broad inhibitory spectrum of this bacteriocin may be of interest as a potential natural biopreservative in the food industry, particularly in post-processed and ready-to-eat food.

Preventing Ototoxic Synergy of Prior Noise Trauma during Aminoglycoside Therapy

DTIC Science & Technology

2017-06-01

with aminoglycoside antibiotics that have broad-spectrum bactericidal activity for treating or preventing life-threatening infections. However...with aminoglycoside antibiotics that have broad- spectrum bactericidal activity for treating or preventing life-threatening infections. However...aminoglycoside uptake. What was accomplished under these goals? 1) Major activities Due to lab relocation, the project was interrupted in 2015, and

Friends or Foes? Host defense (antimicrobial) peptides and proteins in human skin diseases.

PubMed

Niyonsaba, François; Kiatsurayanon, Chanisa; Chieosilapatham, Panjit; Ogawa, Hideoki

2017-11-01

Host defense peptides/proteins (HDPs), also known as antimicrobial peptides/proteins (AMPs), are key molecules in the cutaneous innate immune system. AMPs/HDPs historically exhibit broad-spectrum killing activity against bacteria, enveloped viruses, fungi and several parasites. Recently, AMPs/HDPs were shown to have important biological functions, including inducing cell proliferation, migration and differentiation; regulating inflammatory responses; controlling the production of various cytokines/chemokines; promoting wound healing; and improving skin barrier function. Despite the fact that AMPs/HDPs protect our body, several studies have hypothesized that these molecules actively contribute to the pathogenesis of various skin diseases. For example, AMPs/HDPs play crucial roles in the pathological processes of psoriasis, atopic dermatitis, rosacea, acne vulgaris, systemic lupus erythematosus and systemic sclerosis. Thus, AMPs/HDPs may be a double-edged sword, promoting cutaneous immunity while simultaneously initiating the pathogenesis of some skin disorders. This review will describe the most common skin-derived AMPs/HDPs (defensins, cathelicidins, S100 proteins, ribonucleases and dermcidin) and discuss the biology and both the positive and negative aspects of these AMPs/HDPs in skin inflammatory/infectious diseases. Understanding the regulation, functions and mechanisms of AMPs/HDPs may offer new therapeutic opportunities in the treatment of various skin disorders. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Identification, Purification and Characterization of Laterosporulin, a Novel Bacteriocin Produced by Brevibacillus sp. Strain GI-9

PubMed Central

Singh, Pradip Kumar; Chittpurna; Ashish; Sharma, Vikas; Patil, Prabhu B.; Korpole, Suresh

2012-01-01

Background Bacteriocins are antimicrobial peptides that are produced by bacteria as a defense mechanism in complex environments. Identification and characterization of novel bacteriocins in novel strains of bacteria is one of the important fields in bacteriology. Methodology/Findings The strain GI-9 was identified as Brevibacillus sp. by 16 S rRNA gene sequence analysis. The bacteriocin produced by strain GI-9, namely, laterosporulin was purified from supernatant of the culture grown under optimal conditions using hydrophobic interaction chromatography and reverse-phase HPLC. The bacteriocin was active against a wide range of Gram-positive and Gram-negative bacteria. MALDI-TOF experiments determined the precise molecular mass of the peptide to be of 5.6 kDa and N-terminal sequencing of the thermo-stable peptide revealed low similarity with existing antimicrobial peptides. The putative open reading frame (ORF) encoding laterosporulin and its surrounding genomic region was fished out from the draft genome sequence of GI-9. Sequence analysis of the putative bacteriocin gene did not show significant similarity to any reported bacteriocin producing genes in database. Conclusions We have identified a bacteriocin producing strain GI-9, belonging to the genus Brevibacillus sp. Biochemical and genomic characterization of laterosporulin suggests it as a novel bacteriocin with broad spectrum antibacterial activity. PMID:22403615

Identification, purification and characterization of laterosporulin, a novel bacteriocin produced by Brevibacillus sp. strain GI-9.

PubMed

Singh, Pradip Kumar; Chittpurna; Ashish; Sharma, Vikas; Patil, Prabhu B; Korpole, Suresh

2012-01-01

Bacteriocins are antimicrobial peptides that are produced by bacteria as a defense mechanism in complex environments. Identification and characterization of novel bacteriocins in novel strains of bacteria is one of the important fields in bacteriology. The strain GI-9 was identified as Brevibacillus sp. by 16 S rRNA gene sequence analysis. The bacteriocin produced by strain GI-9, namely, laterosporulin was purified from supernatant of the culture grown under optimal conditions using hydrophobic interaction chromatography and reverse-phase HPLC. The bacteriocin was active against a wide range of Gram-positive and Gram-negative bacteria. MALDI-TOF experiments determined the precise molecular mass of the peptide to be of 5.6 kDa and N-terminal sequencing of the thermo-stable peptide revealed low similarity with existing antimicrobial peptides. The putative open reading frame (ORF) encoding laterosporulin and its surrounding genomic region was fished out from the draft genome sequence of GI-9. Sequence analysis of the putative bacteriocin gene did not show significant similarity to any reported bacteriocin producing genes in database. We have identified a bacteriocin producing strain GI-9, belonging to the genus Brevibacillus sp. Biochemical and genomic characterization of laterosporulin suggests it as a novel bacteriocin with broad spectrum antibacterial activity.

Microbial Etiology of Pneumonia: Epidemiology, Diagnosis and Resistance Patterns.

PubMed

Cilloniz, Catia; Martin-Loeches, Ignacio; Garcia-Vidal, Carolina; San Jose, Alicia; Torres, Antoni

2016-12-16

Globally, pneumonia is a serious public health concern and a major cause of mortality and morbidity. Despite advances in antimicrobial therapies, microbiological diagnostic tests and prevention measures, pneumonia remains the main cause of death from infectious disease in the world. An important reason for the increased global mortality is the impact of pneumonia on chronic diseases, along with the increasing age of the population and the virulence factors of the causative microorganism. The increasing number of multidrug-resistant bacteria, difficult-to-treat microorganisms, and the emergence of new pathogens are a major problem for clinicians when deciding antimicrobial therapy. A key factor for managing and effectively guiding appropriate antimicrobial therapy is an understanding of the role of the different causative microorganisms in the etiology of pneumonia, since it has been shown that the adequacy of initial antimicrobial therapy is a key factor for prognosis in pneumonia. Furthermore, broad-spectrum antibiotic therapies are sometimes given until microbiological results are available and de-escalation cannot be performed quickly. This review provides an overview of microbial etiology, resistance patterns, epidemiology and microbial diagnosis of pneumonia.

Human milk inactivates pathogens individually, additively, and synergistically.

PubMed

Isaacs, Charles E

2005-05-01

Breast-feeding can reduce the incidence and the severity of gastrointestinal and respiratory infections in the suckling neonate by providing additional protective factors to the infant's mucosal surfaces. Human milk provides protection against a broad array of infectious agents through redundancy. Protective factors in milk can target multiple early steps in pathogen replication and target each step with more than one antimicrobial compound. The antimicrobial activity in human milk results from protective factors working not only individually but also additively and synergistically. Lipid-dependent antimicrobial activity in milk results from the additive activity of all antimicrobial lipids and not necessarily the concentration of one particular lipid. Antimicrobial milk lipids and peptides can work synergistically to decrease both the concentrations of individual compounds required for protection and, as importantly, greatly reduce the time needed for pathogen inactivation. The more rapidly pathogens are inactivated the less likely they are to establish an infection. The total antimicrobial protection provided by human milk appears to be far more than can be elucidated by examining protective factors individually.

Next-Generation Probiotics Targeting Clostridium difficile through Precursor-Directed Antimicrobial Biosynthesis

PubMed Central

Auchtung, Jennifer; Brown, Aaron; Boonma, Prapaporn; Oezguen, Numan; Ross, Caná L.; Luna, Ruth Ann; Runge, Jessica; Versalovic, James; Peniche, Alex; Dann, Sara M.; Britton, Robert A.; Haag, Anthony; Savidge, Tor C.

2017-01-01

ABSTRACT Integration of antibiotic and probiotic therapy has the potential to lessen the public health burden of antimicrobial-associated diseases. Clostridium difficile infection (CDI) represents an important example where the rational design of next-generation probiotics is being actively pursued to prevent disease recurrence. Because intrinsic resistance to clinically relevant antibiotics used to treat CDI (vancomycin, metronidazole, and fidaxomicin) is a desired trait in such probiotic species, we screened several bacteria and identified Lactobacillus reuteri to be a promising candidate for adjunct therapy. Human-derived L. reuteri bacteria convert glycerol to the broad-spectrum antimicrobial compound reuterin. When supplemented with glycerol, strains carrying the pocR gene locus were potent reuterin producers, with L. reuteri 17938 inhibiting C. difficile growth at a level on par with the level of growth inhibition by vancomycin. Targeted pocR mutations and complementation studies identified reuterin to be the precursor-induced antimicrobial agent. Pathophysiological relevance was demonstrated when the codelivery of L. reuteri with glycerol was effective against C. difficile colonization in complex human fecal microbial communities, whereas treatment with either glycerol or L. reuteri alone was ineffective. A global unbiased microbiome and metabolomics analysis independently confirmed that glycerol precursor delivery with L. reuteri elicited changes in the composition and function of the human microbial community that preferentially targets C. difficile outgrowth and toxicity, a finding consistent with glycerol fermentation and reuterin production. Antimicrobial resistance has thus been successfully exploited in the natural design of human microbiome evasion of C. difficile, and this method may provide a prototypic precursor-directed probiotic approach. Antibiotic resistance and substrate bioavailability may therefore represent critical new determinants of probiotic efficacy in clinical trials. PMID:28760934

Antimicrobial Peptides: A Promising Therapeutic Strategy in Tackling Antimicrobial Resistance.

PubMed

Nuti, Ramya; Goud, Nerella S; Saraswati, A Prasanth; Alvala, Ravi; Alvala, Mallika

2017-01-01

Antimicrobial resistance (AMR) has posed a serious threat to global public health and it requires immediate action, preferably long term. Current drug therapies have failed to curb this menace due to the ability of microbes to circumvent the mechanisms through which the drugs act. From the drug discovery point of view, the majority of drugs currently employed for antimicrobial therapy are small molecules. Recent trends reveal a surge in the use of peptides as drug candidates as they offer remarkable advantages over small molecules. Newer synthetic strategies like organometalic complexes, Peptide-polymer conjugates, solid phase, liquid phase and recombinant DNA technology encouraging the use of peptides as therapeutic agents with a host of chemical functions, and tailored for specific applications. In the last decade, many peptide based drugs have been successfully approved by the Food and Drug Administration (FDA). This success can be attributed to their high specificity, selectivity and efficacy, high penetrability into the tissues, less immunogenicity and less tissue accumulation. Considering the enormity of AMR, the use of Antimicrobial Peptides (AMPs) can be a viable alternative to current therapeutics strategies. AMPs are naturally abundant allowing synthetic chemists to develop semi-synthetics peptide molecules. AMPs have a broad spectrum of activity towards microbes and they possess the ability to bypass the resistance induction mechanisms of microbes. The present review focuses on the potential applications of AMPs against various microbial disorders and their future prospects. Several resistance mechanisms and their strategies have also been discussed to highlight the importance in the current scenario. Breakthroughs in AMP designing, peptide synthesis and biotechnology have shown promise in tackling this challenge and has revived the interest of using AMPs as an important weapon in fighting AMR. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Antibacterial and antiviral study of dialdehyde polysaccharides

NASA Astrophysics Data System (ADS)

Song, Le

Concerns for microbial contamination and infection to the general population, especially the spread of drug-resistant microorganisms, have greatly increased. Polymeric biocides have been found to be a feasible strategy to inactivate drug-resistant bacteria. However, current polymeric biocide systems involve multi-step chemical reactions and they are not cost-effective. Desirable antimicrobial systems need to be designed to be environmentally friendly, broad-spectrum effective against microorganisms, flexible for various delivery methods and economically affordable. We demonstrated that dialdehyde polysaccharides (including dialdehyde starch and dialdehdye cellulose) were broad-spectrum polymeric biocides against gram-positive/negative bacteria, bacteriophages and human virus. These polymers can be easily converted from starch and cellulose through one-step periodate oxidation. Destructions of microorganism by dialdehyde polysaccharides have been achieved in aqueous suspension or by solid surface contact. The dialdehdye functions of dialdehdye polysaccharides were found to be the dominant action against microorganism. The reactivity of the dialdehyde functionality was found to be pH-dependent as well as related to the dispersion of dialdehyde polysaccharides. Degradation of dialdehyde starch during cooking was confirmed. Degradation of dialdehyde starch was more liable in alkaline condition. Carboxylic acid and conjugated aldehyde functionalities were the two main degradation products, confirmed from the spectroscopic studies. The pH effect on the polysaccharide structure and the corresponding antimicrobial activity was very complicated. No decisive conclusions could be obtained from this study. Liner inactivation kinetics was found for dialdehyde starch aqueous suspension against bacteria. This linear inactivation kinetics was derived from the pseudo-first chemical reaction between the dialdehyde starch and the bacteria. The established inactivation kinetics was successfully predicated the response of bacteria to dialdehyde starch with time. Inactivation of bacteria by dialdehyde starch was speculated to be the crosslinking-interaction between the dialdehyde starch and the bacterial surface. Amino groups of bacterial surfaces were blocked by dialdehyde starch. This crosslinking action was also suggested from the preliminary study of the bacterial dehydrogenase activity. However, membrane damage was found in the dialdehdye starch treated bacteria from the fluorescent study.

Silver enhances antibiotic activity against gram-negative bacteria.

PubMed

Morones-Ramirez, J Ruben; Winkler, Jonathan A; Spina, Catherine S; Collins, James J

2013-06-19

A declining pipeline of clinically useful antibiotics has made it imperative to develop more effective antimicrobial therapies, particularly against difficult-to-treat Gram-negative pathogens. Silver has been used as an antimicrobial since antiquity, yet its mechanism of action remains unclear. We show that silver disrupts multiple bacterial cellular processes, including disulfide bond formation, metabolism, and iron homeostasis. These changes lead to increased production of reactive oxygen species and increased membrane permeability of Gram-negative bacteria that can potentiate the activity of a broad range of antibiotics against Gram-negative bacteria in different metabolic states, as well as restore antibiotic susceptibility to a resistant bacterial strain. We show both in vitro and in a mouse model of urinary tract infection that the ability of silver to induce oxidative stress can be harnessed to potentiate antibiotic activity. Additionally, we demonstrate in vitro and in two different mouse models of peritonitis that silver sensitizes Gram-negative bacteria to the Gram-positive-specific antibiotic vancomycin, thereby expanding the antibacterial spectrum of this drug. Finally, we used silver and antibiotic combinations in vitro to eradicate bacterial persister cells, and show both in vitro and in a mouse biofilm infection model that silver can enhance antibacterial action against bacteria that produce biofilms. This work shows that silver can be used to enhance the action of existing antibiotics against Gram-negative bacteria, thus strengthening the antibiotic arsenal for fighting bacterial infections.

Cationic antimicrobial polymers and their assemblies.

PubMed

Carmona-Ribeiro, Ana Maria; de Melo Carrasco, Letícia Dias

2013-05-10

Cationic compounds are promising candidates for development of antimicrobial agents. Positive charges attached to surfaces, particles, polymers, peptides or bilayers have been used as antimicrobial agents by themselves or in sophisticated formulations. The main positively charged moieties in these natural or synthetic structures are quaternary ammonium groups, resulting in quaternary ammonium compounds (QACs). The advantage of amphiphilic cationic polymers when compared to small amphiphilic molecules is their enhanced microbicidal activity. Besides, many of these polymeric structures also show low toxicity to human cells; a major requirement for biomedical applications. Determination of the specific elements in polymers, which affect their antimicrobial activity, has been previously difficult due to broad molecular weight distributions and random sequences characteristic of radical polymerization. With the advances in polymerization control, selection of well defined polymers and structures are allowing greater insight into their structure-antimicrobial activity relationship. On the other hand, antimicrobial polymers grafted or self-assembled to inert or non inert vehicles can yield hybrid antimicrobial nanostructures or films, which can act as antimicrobials by themselves or deliver bioactive molecules for a variety of applications, such as wound dressing, photodynamic antimicrobial therapy, food packing and preservation and antifouling applications.

Cationic Antimicrobial Polymers and Their Assemblies

PubMed Central

Carmona-Ribeiro, Ana Maria; de Melo Carrasco, Letícia Dias

2013-01-01

Cationic compounds are promising candidates for development of antimicrobial agents. Positive charges attached to surfaces, particles, polymers, peptides or bilayers have been used as antimicrobial agents by themselves or in sophisticated formulations. The main positively charged moieties in these natural or synthetic structures are quaternary ammonium groups, resulting in quaternary ammonium compounds (QACs). The advantage of amphiphilic cationic polymers when compared to small amphiphilic molecules is their enhanced microbicidal activity. Besides, many of these polymeric structures also show low toxicity to human cells; a major requirement for biomedical applications. Determination of the specific elements in polymers, which affect their antimicrobial activity, has been previously difficult due to broad molecular weight distributions and random sequences characteristic of radical polymerization. With the advances in polymerization control, selection of well defined polymers and structures are allowing greater insight into their structure-antimicrobial activity relationship. On the other hand, antimicrobial polymers grafted or self-assembled to inert or non inert vehicles can yield hybrid antimicrobial nanostructures or films, which can act as antimicrobials by themselves or deliver bioactive molecules for a variety of applications, such as wound dressing, photodynamic antimicrobial therapy, food packing and preservation and antifouling applications. PMID:23665898

Concomitant pulmonary infection with Nocardia transvalensis and Aspergillus ustus in lung transplantation.

PubMed

Cabada, Miguel M; Nishi, Shawn P; Lea, Alfred S; Schnadig, Vicki; Lombard, Gisele A; Lick, Scott D; Valentine, Vincent G

2010-08-01

Lung infections with Nocardia and Aspergillus spp in lung transplant recipients (LTRs) create diagnostic and therapeutic challenges. The present case illustrates the difficulties in identifying these pathogens in LTRs. A high degree of clinical suspicion and aggressive early management are required to ensure good outcomes. Although prospective data on treating these conditions are scarce, the empiric use of combination broad-spectrum anti-microbials initially seems prudent. Copyright (c) 2010 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Kefiran-alginate gel microspheres for oral delivery of ciprofloxacin.

PubMed

Blandón, Lina M; Islan, German A; Castro, Guillermo R; Noseda, Miguel D; Thomaz-Soccol, Vanete; Soccol, Carlos R

2016-09-01

Ciprofloxacin is a broad-spectrum antibiotic associated with gastric and intestinal side effects after extended oral administration. Alginate is a biopolymer commonly employed in gel synthesis by ionotropic gelation, but unstable in the presence of biological metal-chelating compounds and/or under dried conditions. Kefiran is a microbial biopolymer able to form gels with the advantage of displaying antimicrobial activity. In the present study, kefiran-alginate gel microspheres were developed to encapsulate ciprofloxacin for antimicrobial controlled release and enhanced bactericidal effect against common pathogens. Scanning electron microscopy (SEM) analysis of the hybrid gel microspheres showed a spherical structure with a smoother surface compared to alginate gel matrices. In vitro release of ciprofloxacin from kefiran-alginate microspheres was less than 3.0% and 5.0% at pH 1.2 (stomach), and 5.0% and 25.0% at pH 7.4 (intestine) in 3 and 21h, respectively. Fourier transform infrared spectroscopy (FTIR) of ciprofloxacin-kefiran showed the displacement of typical bands of ciprofloxacin and kefiran, suggesting a cooperative interaction by hydrogen bridges between both molecules. Additionally, the thermal analysis of ciprofloxacin-kefiran showed a protective effect of the biopolymer against ciprofloxacin degradation at high temperatures. Finally, antimicrobial assays of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhymurium, and Staphylococcus aureus demonstrated the synergic effect between ciprofloxacin and kefiran against the tested microorganisms. Copyright © 2016 Elsevier B.V. All rights reserved.

Antimicrobial Polymers: Mimicking Amino Acid Functionali ty, Sequence Control and Three-dimensional Structure of Host-defen se Peptides.

PubMed

Hartlieb, Matthias; Williams, Elizabeth G L; Kuroki, Agnès; Perrier, Sébastien; Locock, Katherine E S

2017-01-01

Peptides and proteins control and direct all aspects of cellular function and communication. Having been honed by nature for millions of years, they also typically display an unsurpassed specificity for their biological targets. This underlies the continued focus on peptides as promising drug candidates. However, the development of peptides into viable drugs is hampered by their lack of chemical and pharmacokinetic stability and the cost of large scale production. One method to overcome such hindrances is to develop polymer systems that are able to retain the important structural features of these biologically active peptides, while being cheaper and easier to produce and manipulate chemically. This review illustrates these principles using examples of polymers designed to mimic antimicrobial host-defence peptides. The host-defence peptides have been identified as some of the most important leads for the next generation of antibiotics as they typically exhibit broad spectrum antimicrobial ability, low toxicity toward human cells and little susceptibility to currently known mechanisms of bacterial resistance. Their movement from the bench to clinic is yet to be realised, however, due to the limitations of these peptides as drugs. The literature provides a number of examples of polymers that have been able to mimic these peptides through all levels of structure, starting from specific amino acid sidechains, through to more global features such as overall charge, molecular weight and threedimensional structure (e.g. α-helical). The resulting optimised polymers are able retain the activity profile of the peptides, but within a synthetic macromolecular construct that may be better suited to the development of a new generation of antimicrobial therapeutics. Such work has not only produced important new leads to combat the growing threat of antibiotic resistance, but may also open up new ways for polymers to mimic other important classes of biologically active peptides. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Choline and Geranate Deep Eutectic Solvent as a Broad-Spectrum Antiseptic Agent for Preventive and Therapeutic Applications.

PubMed

Zakrewsky, Michael; Banerjee, Amrita; Apte, Sanjana; Kern, Theresa L; Jones, Mattie R; Sesto, Rico E Del; Koppisch, Andrew T; Fox, David T; Mitragotri, Samir

2016-06-01

Antiseptic agents are the primary arsenal to disinfect skin and prevent pathogens spreading within the host as well as into the surroundings; however the Food and Drug Administration published a report in 2015 requiring additional validation of nearly all current antiseptic agents before their continued use can be allowed. This vulnerable position calls for urgent identification of novel antiseptic agents. Recently, the ability of a deep eutectic, Choline And Geranate (CAGE), to treat biofilms of Pseudomonas aeruginosa and Salmonella enterica was demonstrated. Here it is reported that CAGE exhibits broad-spectrum antimicrobial activity against a number of drug-resistant bacteria, fungi, and viruses including clinical isolates of Mycobacterium tuberculosis, Staphylococcus aureus, and Candida albicans as well as laboratory strains of Herpes Simplex Virus. Studies in human keratinocytes and mice show that CAGE affords negligible local or systemic toxicity, and an ≈180-14 000-fold improved efficacy/toxicity ratio over currently used antiseptic agents. Further, CAGE penetrates deep into the dermis and treats pathogens located in deep skin layers as confirmed by the ability of CAGE in vivo to treat Propionibacterium acnes infection. In combination, the results clearly demonstrate CAGE holds promise as a transformative platform antiseptic agent for preventive as well as therapeutic applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Antimicrobial properties of zeolite-X and zeolite-A ion-exchanged with silver, copper, and zinc against a broad range of microorganisms.

PubMed

Demirci, Selami; Ustaoğlu, Zeynep; Yılmazer, Gonca Altın; Sahin, Fikrettin; Baç, Nurcan

2014-02-01

Zeolites are nanoporous alumina silicates composed of silicon, aluminum, and oxygen in a framework with cations, water within pores. Their cation contents can be exchanged with monovalent or divalent ions. In the present study, the antimicrobial (antibacterial, anticandidal, and antifungal) properties of zeolite type X and A, with different Al/Si ratio, ion exchanged with Ag(+), Zn(2+), and Cu(2+) ions were investigated individually. The study presents the synthesis and manufacture of four different zeolite types characterized by scanning electron microscopy and X-ray diffraction. The ion loading capacity of the zeolites was examined and compared with the antimicrobial characteristics against a broad range of microorganisms including bacteria, yeast, and mold. It was observed that Ag(+) ion-loaded zeolites exhibited more antibacterial activity with respect to other metal ion-embedded zeolite samples. The results clearly support that various synthetic zeolites can be ion exchanged with Ag(+), Zn(2+), and Cu(2+) ions to acquire antimicrobial properties or ion-releasing characteristics to provide prolonged or stronger activity. The current study suggested that zeolite formulations could be combined with various materials used in manufacturing medical devices, surfaces, textiles, or household items where antimicrobial properties are required.

Antibiotic exposure in neonates and early adverse outcomes: a systematic review and meta-analysis.

PubMed

Esaiassen, Eirin; Fjalstad, Jon Widding; Juvet, Lene Kristine; van den Anker, John N; Klingenberg, Claus

2017-07-01

To systematically review and meta-analyse the relationship between antibiotic exposure in neonates and the following early adverse outcomes: necrotizing enterocolitis (NEC), invasive fungal infections (IFIs) and/or death. Data sources were PubMed, Embase, Medline and the Cochrane Database (to December 2016), supplemented by manual searches of reference lists. Randomized controlled trials (RCTs) and observational studies were included if they provided data on different categories of antibiotic exposures (yes versus no, long versus short duration, and/or broad- versus narrow-spectrum regimens) and the risk of developing NEC, IFI and/or death in the neonatal period. Two reviewers extracted data and evaluated the risk of bias using the Cochrane Handbook, adapted to include observational studies. When appropriate, meta-analyses were conducted using the random-effect model. We identified 9 RCTs and 38 observational studies. The quality of the majority of studies was poor to moderate. There was a significant association between prolonged antibiotic exposure and an increased risk of NEC in five observational studies (5003 participants) and/or risk of death in five observational studies (13 534 participants). Eleven of 15 studies with data on broad- versus narrow-spectrum regimens reported an increased risk of IFI after broad-spectrum antibiotic exposure, in particular with third-generation cephalosporins and carbapenems. Meta-analysis was limited by few and old RCTs, insufficient sample sizes and diversity of antibiotic exposure and outcomes reported. Prolonged antibiotic exposure in uninfected preterm infants is associated with an increased risk of NEC and/or death, and broad-spectrum antibiotic exposure is associated with an increased risk of IFI. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Identification of Inonotus obliquus polysaccharide with broad-spectrum antiviral activity against multi-feline viruses.

PubMed

Tian, Jin; Hu, Xiaoliang; Liu, Dafei; Wu, Hongxia; Qu, Liandong

2017-02-01

Inonotus obliquus polysaccharides (IOPs) are a potential drug for the prevention and treatment of cancer, cardiopathy, diabetes, AIDs, pancreatitis and other diseases. In this study, we found that IOP can act as a broad-spectrum antiviral drug against feline viruses in the in vitro experiment. Using cell models of feline calicivirus (FCV), we demonstrated that IOP treatment was capable of exhibiting anti-FCV strain F9 activity in cell-based assays and also showed low cytotoxicity. Investigation of the mechanism of action of the compound revealed that IOP treatment induces its inhibitory actions directly on virus particles through blocking viral binding/absorpting. The inhibitory activity against other FCV isolates from China was also identified. More importantly, we found that IOP exhibited broad-spectrum antiviral activity against the feline herpesvirus 1, feline influenza virus H3N2 and H5N6, feline panleukopenia virus and feline infectious peritonitis virus that can contribute to respiratory and gastrointestinal diseases in cats. These findings suggest that IOP may be a potential broad-spectrum antiviral drug against feline viruses. Copyright © 2016 Elsevier B.V. All rights reserved.

Antimicrobial Peptides and Their Therapeutic Potential for Bacterial Skin Infections and Wounds

PubMed Central

Pfalzgraff, Anja; Brandenburg, Klaus; Weindl, Günther

2018-01-01

Alarming data about increasing resistance to conventional antibiotics are reported, while at the same time the development of new antibiotics is stagnating. Skin and soft tissue infections (SSTIs) are mainly caused by the so called ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) which belong to the most recalcitrant bacteria and are resistant to almost all common antibiotics. S. aureus and P. aeruginosa are the most frequent pathogens isolated from chronic wounds and increasing resistance to topical antibiotics has become a major issue. Therefore, new treatment options are urgently needed. In recent years, research focused on the development of synthetic antimicrobial peptides (AMPs) with lower toxicity and improved activity compared to their endogenous counterparts. AMPs appear to be promising therapeutic options for the treatment of SSTIs and wounds as they show a broad spectrum of antimicrobial activity, low resistance rates and display pivotal immunomodulatory as well as wound healing promoting activities such as induction of cell migration and proliferation and angiogenesis. In this review, we evaluate the potential of AMPs for the treatment of bacterial SSTIs and wounds and provide an overview of the mechanisms of actions of AMPs that contribute to combat skin infections and to improve wound healing. Bacteria growing in biofilms are more resistant to conventional antibiotics than their planktonic counterparts due to limited biofilm penetration and distinct metabolic and physiological functions, and often result in chronification of infections and wounds. Thus, we further discuss the feasibility of AMPs as anti-biofilm agents. Finally, we highlight perspectives for future therapies and which issues remain to bring AMPs successfully to the market. PMID:29643807

Ru(CO)3Cl(Glycinate) (CORM-3): A Carbon Monoxide–Releasing Molecule with Broad-Spectrum Antimicrobial and Photosensitive Activities Against Respiration and Cation Transport in Escherichia coli

PubMed Central

Wilson, Jayne Louise; Jesse, Helen E.; Hughes, Bethan; Lund, Victoria; Naylor, Kathryn; Davidge, Kelly S.; Cook, Gregory M.; Mann, Brian E.

2013-01-01

Abstract Aims: Carbon monoxide (CO) delivered to cells and tissues by CO-releasing molecules (CO-RMs) has beneficial and toxic effects not mimicked by CO gas. The metal carbonyl Ru(CO)3Cl(glycinate) (CORM-3) is a novel, potent antimicrobial agent. Here, we established its mode of action. Results: CORM-3 inhibits respiration in several bacterial and yeast pathogens. In anoxic Escherichia coli suspensions, CORM-3 first stimulates, then inhibits respiration, but much higher concentrations of CORM-3 than of a classic protonophore are required for stimulation. Proton translocation measurements (H+/O quotients, i.e., H+ extrusion on pulsing anaerobic cells with O2) show that respiratory stimulation cannot be attributed to true “uncoupling,” that is, dissipation of the protonmotive force, or to direct stimulation of oxidase activity. Our data are consistent with CORM-3 facilitating the electrogenic transmembrane movement of K+ (or Na+), causing a stimulation of respiration and H+ pumping to compensate for the transient drop in membrane potential (ΔΨ). The effects on respiration are not mimicked by CO gas or control Ru compounds that do not release CO. Inhibition of respiration and loss of bacterial viability elicited by CORM-3 are reversible by white light, unambiguously identifying heme-containing oxidase(s) as target(s). Innovation: This is the most complete study to date of the antimicrobial action of a CO-RM. Noteworthy are the demonstration of respiratory stimulation, electrogenic ion transport, and photosensitive activity, establishing terminal oxidases and ion transport as primary targets. Conclusion: CORM-3 has multifaceted effects: increased membrane permeability, inhibition of terminal oxidases, and perhaps other unidentified mechanisms underlie its effectiveness in tackling microbial pathogenesis. Antioxid. Redox Signal. 19, 497–509. PMID:23186316

Phytochemical profiles and antimicrobial activity of aromatic Malaysian herb extracts against food-borne pathogenic and food spoilage microorganisms.

PubMed

Aziman, Nurain; Abdullah, Noriham; Noor, Zainon Mohd; Kamarudin, Wan Saidatul Syida Wan; Zulkifli, Khairusy Syakirah

2014-04-01

Preliminary phytochemical and flavonoid compounds of aqueous and ethanolic extracts of 6 aromatic Malaysian herbs were screened and quantified using Reverse-Phase High Performance Liquid Chromatography (RP-HPLC). The herbal extracts were tested for their antimicrobial activity against 10 food-borne pathogenic and food spoilage microorganisms using disk diffusion assay. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)/minimum fungicidal concentration (MFC) of herbal extracts were determined. In the phytochemical screening process, both aqueous and ethanolic extracts of P. hydropiper exhibited presence of all 7 tested phytochemical compounds. Among all herbal extracts, the aqueous P. hydropiper and E. elatior extracts demonstrated the highest antibacterial activity against 7 tested Gram-positive and Gram-negative bacteria with diameter ranging from 7.0 to 18.5 mm and 6.5 to 19 mm, respectively. The MIC values for aqueous and ethanolic extracts ranged from 18.75 to 175 mg/mL and 0.391 to 200 mg/mL, respectively while the MBC/MFC values for aqueous and ethanolic extracts ranged from 25 to 200 mg/mL and 3.125 to 50 mg/mL, respectively. Major types of bioactive compounds in aqueous P. hydropiper and E. elatior extracts were identified using RP-HPLC instrument. Flavonoids found in these plants were epi-catechin, quercetin, and kaempferol. The ability of aqueous Persicaria hydropiper (L.) H. Gross and Etlingera elatior (Jack) R.M. Sm. extracts to inhibit the growth of bacteria is an indication of its broad spectrum antimicrobial potential. Hence these herbal extracts may be used as natural preservative to improve the safety and shelf-life of food and pharmaceutical products. © 2014 Institute of Food Technologists®

Activity of Topical Antimicrobial Agents Against Multidrug-Resistant Bacteria Recovered from Burn Patients

DTIC Science & Technology

2010-01-01

produced by Pseudomonas fluorescens [19] Inhibition of RNA and protein synthesis by targeting the isoleucine-binding site on the isoleucyl-transfer-RNA...multidrug-resistant (MDR) bacteria. We compared two methods of determining topical antimicrobial susceptibilities. Methods: Isolates of Pseudomonas ...aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), extended spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae, and

Different Interfacial Behaviors of N- and C-Terminus Cysteine-Modified Cecropin P1 Chemically Immobilized onto Polymer Surface

DTIC Science & Technology

2013-08-06

naturally occurring antimicrobial peptides (AMPs) have been studied as an alternative with a broad range of activity and binding affinity toward...microorganisms.10−16 For example, chemically immo- bilized cecropin P1, cecropin A, cecropin B, and other antimicrobial peptides have demonstrated promise for...Autom. 2006, 11 (6), 341−351. (10) Gregory, K.; Mello, C. M. Immobilization of Escherichia coli cells by use of the antimicrobial peptide cecropin P1

Clinical benefits of antimicrobial de-escalation in adults with community-onset monomicrobial Escherichia coli, Klebsiella species and Proteus mirabilis bacteremia.

PubMed

Lee, Ching-Chi; Wang, Jiun-Ling; Lee, Chung-Hsun; Hung, Yuan-Pin; Hong, Ming-Yuan; Tang, Hung-Jen; Ko, Wen-Chien

2017-09-01

The clinical benefits of an antimicrobial de-escalation strategy were compared with those of a no-switch strategy in bacteremic patients. Adults with community-onset monomicrobial Escherichia coli, Klebsiella species and Proteus mirabilis bacteremia treated empirically using broad-spectrum beta-lactams, including third-generation cephalosporins (GCs), fourth-GC or carbapenems, were treated definitively with first- or second-GCs (de-escalation group), the same regimens as empirical antibiotics (no-switch group), or antibiotics with a broader-spectrum than empirical antibiotics (escalation group). The eligible 454 adults were categorized as the de-escalation (231 patients, 50.9%), no-switch (177, 39.0%), and escalation (46, 10.1%) groups. Patients with de-escalation therapy were more often female, had less critical illness and fatal comorbidity, and had a higher survival rate than patients in the other two groups. After propensity score matching in the de-escalation and no-switch groups, critical illness at onset (Pitt bacteremia score ≥ 4; 16.5% vs. 12.7%; P = 0.34) or day 3 (2.5% vs. 2.5%; P = 1.00), fatal comorbidity (16.5% vs. 21.5%; P = 0.25), time to defervescence (4.6 vs. 4.7 days; P = 0.89), hospital stays (11.5 vs. 10.3 days; P = 0.13) and 4-week crude mortality rate (4.4% vs. 4.4%; P = 1.00) were similar. However, lower antibiotic cost (mean: 212.1 vs. 395.6 US$, P <0.001) and fewer complications of bloodstream infections due to resistant pathogens (0% vs. 5.1%, P = 0.004) were observed in the de-escalation group. De-escalation to narrower-spectrum cephalosporins is safe and cost-effective for adults with community-onset EKP bacteremia stabilized by empirical broad-spectrum beta-lactams. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.