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1

Vaccines for Moraxella catarrhalis  

Microsoft Academic Search

Vaccine development for Moraxella catarrhalis is in the antigen identification stage. M. catarrhalis does not appear to synthesize secreted antigens such as exotoxins, nor does it appear to possess a carbohydrate capsule. Modified forms of these antigens are usually good vaccine components. There is some interest in whole bacterial cells and membrane fractions, but the search has largely focused on

John C McMichael

2000-01-01

2

Moraxella catarrhalis: from emerging to established pathogen  

Microsoft Academic Search

Moraxella catarrhalis (formerly known as Branhamella catarrhalis) has\\u000a emerged as a significant bacterial pathogen of humans over the past two\\u000a decades. During this period, microbiological and molecular diagnostic\\u000a techniques have been developed and improved for M. catarrhalis, allowing\\u000a the adequate determination and taxonomic positioning of this pathogen.\\u000a Over the same period, studies have revealed its involvement in respiratory\\u000a (e.g., sinusitis,

Cees M. Verduin; Cees Hol; A. Fleer; H. van Dijk; Belkum van A. F

2002-01-01

3

Moraxella catarrhalis: from emerging to established pathogen.  

PubMed

Moraxella catarrhalis (formerly known as Branhamella catarrhalis) has emerged as a significant bacterial pathogen of humans over the past two decades. During this period, microbiological and molecular diagnostic techniques have been developed and improved for M. catarrhalis, allowing the adequate determination and taxonomic positioning of this pathogen. Over the same period, studies have revealed its involvement in respiratory (e.g., sinusitis, otitis media, bronchitis, and pneumonia) and ocular infections in children and in laryngitis, bronchitis, and pneumonia in adults. The development of (molecular) epidemiological tools has enabled the national and international distribution of M. catarrhalis strains to be established, and has allowed the monitoring of nosocomial infections and the dynamics of carriage. Indeed, such monitoring has revealed an increasing number of B-lactamase-positive M. catarrhalis isolates (now well above 90%), underscoring the pathogenic potential of this organism. Although a number of putative M. catarrhalis virulence factors have been identified and described in detail, their relationship to actual bacterial adhesion, invasion, complement resistance, etc. (and ultimately their role in infection and immunity), has been established in a only few cases. In the past 10 years, various animal models for the study of M. catarrhalis pathogenicity have been described, although not all of these models are equally suitable for the study of human infection. Techniques involving the molecular manipulation of M. catarrhalis genes and antigens are also advancing our knowledge of the host response to and pathogenesis of this bacterial species in humans, as well as providing insights into possible vaccine candidates. This review aims to outline our current knowledge of M. catarrhalis, an organism that has evolved from an emerging to a well-established human pathogen. PMID:11781271

Verduin, Cees M; Hol, Cees; Fleer, André; van Dijk, Hans; van Belkum, Alex

2002-01-01

4

Complement resistance is a virulence factor of Branhamella (Moraxella) catarrhalis  

Microsoft Academic Search

The purpose of this study was to investigate complement resistance in Branhamella (Moraxella) catarrhalis isolated from healthy schoolchildren or sputum-producing adult patients. Two techniques were used: a serum bactericidal assay as the gold standard and an easier ‘culture and spot’ test. Children (age 4–13; n = 303) and patients (n = 1047) showed high colonization\\/infection rates with B. catarrhalis (31%

Cees Hol; Cees M. Verduin; Etienne E. A. Van Dijke; Jan Verhoef; André Fleer; Hans van Dijk

1995-01-01

5

Moraxella catarrhalis: a review of an important human mucosal pathogen  

Microsoft Academic Search

Moraxella catarrhalis has again been recognized as a significant pathogen. The past decade has witnessed an increased amount of research and understanding of the pathogenesis of the organism. This review will summarize the research pertaining to the epidemiology and components of pathogenesis in M. catarrhalis.

Richard Karalus; Anthony Campagnari

2000-01-01

6

Outbreak of Moraxella catarrhalis in a respiratory unit  

Microsoft Academic Search

The clinical and epidemiological features of an outbreak of nosocomial Moraxella catarrhalis infection in a respiratory unit are described. Six isolates from five patients were shown to be indistinguishable by immunoblotting and restriction endonuclease analysis and different from 11 other, unrelated clinical strains.

S J Richards; A P Greening; M C Enright; M G Morgan; H McKenzie

1993-01-01

7

Improved pulsed field gel electrophoresis method for Moraxella catarrhalis.  

PubMed

An improved PFGE method for the molecular typing of Moraxella catarrhalis is described. A modified PulseNet method using higher concentrations of EDTA and proteinase K, together with increased reagent volumes and incubation temperatures resulted in improved results and a more rapid turnaround time compared to PFGE methods currently used. PMID:18586342

Pingault, Nevada M; Lehmann, Deborah; Riley, Thomas V

2008-10-01

8

In vitro activity of roxithromycin against Moraxella catarrhalis.  

PubMed

The in vitro activity of roxithromycin was compared with that of the other antimicrobial agents (erythromycin, tetracycline, ampicillin, and cotrimoxazole) against 188 distinct clinical isolates of Moraxella catarrhalis. Of these, 106 strains (66%) produced beta-lactamase. The MIC90 of roxithromycin was 0.25 micrograms/ml compared with values of 0.5, 1, greater than 8, greater than 8:0.4 micrograms/ml for erythromycin, tetracycline, ampicillin, and sulfamethoxazole-trimethoprim, respectively. These results, allied with its improved pharmacokinetic properties, suggest that roxithromycin should be an effective treatment in children and adults for upper and lower respiratory tract infections caused by M. catarrhalis. PMID:1617926

Spencer, R C; Wheat, P F

1992-01-01

9

Cloning and Expression of the Moraxella catarrhalis Lactoferrin Receptor Genes  

Microsoft Academic Search

The lactoferrin receptor genes from two strains of Moraxella catarrhalis have been cloned and sequenced. The lfr genes are arranged as lbpB followed by lbpA, a gene arrangement found in lactoferrin and transferrin receptor operons from several bacterial species. In addition, a third open reading frame, orf3, is located one nucleotide downstream of lbpA. The deduced lactoferrin binding protein A

RUN-PAN DU; QIJUN WANG; YAN-PING YANG; ANTHONY B. SCHRYVERS; PELE CHONG; MICHEL H. KLEIN; SHEENA M. LOOSMORE

1998-01-01

10

Moraxella catarrhalis in Chronic Obstructive Pulmonary Disease Burden of Disease and Immune Response  

Microsoft Academic Search

Rationale: Moraxella catarrhalis is frequently present in the sputum of adults with chronic obstructive pulmonary disease (COPD). Little is known about the role of M. catarrhalis in this common disease. Objective: To elucidate the burden of disease, the dynamics of car- riage, and immune responses to M. catarrhalis in COPD. Methods: Prospective cohort study of 104 adults with COPD in

Timothy F. Murphy; Aimee L. Brauer; Brydon J. B. Grant; Sanjay Sethi

11

Characterisation of an outer membrane protein of Moraxella catarrhalis.  

PubMed

To elucidate potential vaccine antigens, Moraxella catarrhalis outer membrane proteins (OMPs) were studied. We have previously shown an OMP to be a target for human IgG and have now further characterised this OMP which appears to have a molecular mass of 84 kDa and to be distinct from the 81-kDa OMP, CopB. Human transferrin was shown to bind the 84-kDa OMP alone. N-terminal sequencing of this OMP and purified M. catarrhalis transferrin binding protein B (TbpB) revealed homology both with each other and with the TbpB of Haemophilus influenzae and Neisseria meningitidis. Adsorption of human anti-serum with purified TbpB from two M. catarrhalis strains abolished or reduced binding of IgG to the 84-kDa OMP from three M. catarrhalis isolates. IgG binding to CopB was unaffected. It is clear that the 84-kDa OMP is distinct from CopB and is a likely homologue of TbpB. PMID:9453393

Mathers, K E; Goldblatt, D; Aebi, C; Yu, R; Schryvers, A B; Hansen, E J

1997-11-01

12

The Immunoglobulin D-Binding Protein MID from Moraxella catarrhalis Is Also an Adhesin  

Microsoft Academic Search

The Moraxella catarrhalis immunoglobulin D (IgD)-binding protein (MID) is a 200-kDa outer membrane protein displaying a unique and specific affinity for human IgD. MID is found in the majority of M. catarrhalis strains. In the present paper, we show that MID-expressing M. catarrhalis strains agglutinate human eryth- rocytes and bind to type II alveolar epithelial cells. In contrast, M. catarrhalis

Arne Forsgren; Marta Brant; Mirela Karamehmedovic; Kristian Riesbeck

2003-01-01

13

Mining the Moraxella catarrhalis Genome: Identification of Potential Vaccine Antigens Expressed during Human Infection  

Microsoft Academic Search

Received 12 September 2007\\/Returned for modification 2 November 2007\\/Accepted 22 January 2008 Moraxella catarrhalis is an important cause of respiratory infections in adults and otitis media in children. Developing an effective vaccine would reduce the morbidity, mortality, and costs associated with such infec- tions. An unfinished genome sequence of a strain of M. catarrhalis available in the GenBank database was

Elizabeth A. Ruckdeschel; Charmaine Kirkham; Alan J. Lesse; Zihua Hu; Timothy F. Murphy

2008-01-01

14

Analysis of Antigenic Structure and Human Immune Response to Outer Membrane Protein CD of Moraxella catarrhalis  

Microsoft Academic Search

Moraxella catarrhalis is an important cause of otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD). Outer membrane protein CD (OMP CD) is a 45-kDa protein which is a potential vaccine antigen to prevent infections caused by M. catarrhalis. Eight monoclonal antibodies were used to study the antigenic structure of the OMP

TIMOTHY F. MURPHY; CHARMAINE KIRKHAM; ERNESTO DENARDIN; SANJAY SETHI

1999-01-01

15

Antigenic Specificity of the Mucosal Antibody Response to Moraxella catarrhalis in Chronic Obstructive Pulmonary Disease  

Microsoft Academic Search

Moraxella catarrhalis is an important human mucosal pathogen causing otitis media in children and lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD). Little is known about the mucosal antibody response to M. catarrhalis in adults with COPD. In this study, 10 pairs of well- characterized sputum supernatant samples from adults with COPD who had acquired and

Timothy F. Murphy; Aimee L. Brauer; Christoph Aebi; Sanjay Sethi

2005-01-01

16

Hag Directly Mediates the Adherence of Moraxella catarrhalis to Human Middle Ear Cells  

Microsoft Academic Search

Moraxella catarrhalis is a human pathogen that causes otitis media in young children and lung infections in patients with chronic obstructive pulmonary disease. In this study, the role of the surface protein Hag in the adherence of multiple M. catarrhalis strains was examined. The hag genes of four clinical isolates were disrupted with a spectinomycin resistance cassette, and the binding

Brian Bullard; Serena L. Lipski; Eric R. Lafontaine

2005-01-01

17

Molecular mechanisms of moraxella catarrhalis-induced otitis media.  

PubMed

Moraxella catarrhalis is a Gram-negative bacterium, exclusively present in humans and a leading causative agent of otitis media (OM) in children. Most children (80 %) experience at least one episode of OM by their third birthday and half suffer multiple episodes of infection. Over the last 10 years, increased evidence suggests that M. cat possesses multiple virulence factors which can be carried through biologically active outer membrane vesicles (OMVs) that are themselves able to activate host-immune responses. It has also been noted that multiple toll-like receptors are responsible for M. cat recognition. This review is intended to summarize the key findings and progress in recent years of the molecular mechanisms of M. cat-induced otitis media with particular emphasis on adhesion, invasion, and activation of the host immune system, biofilm formation, and vaccine development. PMID:23934577

Hassan, Ferdaus

2013-10-01

18

Nosocomial transmission clusters and risk factors in Moraxella catarrhalis.  

PubMed

We report an objective examination of nosocomial transmission events derived from long-term (10-year) data from a single medical centre. Cluster analysis, based on the temporal proximity of genetically identical isolates of the respiratory pathogen Moraxella catarrhalis, identified 40 transmission events involving 33 of the 52 genotypes represented by multiple isolates. There was no evidence of highly transmissible or outbreak-prone genotypes. Although most clusters were small (mean size 3.6 isolates) and of short duration (median duration 25 days), clustering accounted for 38.7% of all isolates. Significant risk factors for clustering were multi-bed wards, and winter and spring season, but bacterial antibiotic resistance, manifested as the ability to produce a beta-lactamase was not a risk factor. The use of cluster analysis to identify transmission events and its application to long-term data demonstrate an approach to pathogen transmission that should find wide application beyond hospital populations. PMID:18789178

Levy, F; Leman, S C; Sarubbi, F A; Walker, E S

2009-04-01

19

Moraxella (Branhamella) Catarrhalis Bacteremia in ChildrenA Report of Two Patients and Review of the Literature  

Microsoft Academic Search

We report two cases of Moraxella catarrhalis (M. catarrhalis ) bacteremia in apparently healthy children. One patient had bilateral otitis media and the other had pharyngitis and sinusitis; both patients had uncomplicated clinical courses. A literature review revealed 22 reported cases of M. catarrhalis bacteremia in children, 14 (63%) of which occurred in patients who had no identified underlying condition.

Gretchen A. Meyer; Timothy R. Shope; Norman J. Waecker; Frederick H. Lanningham

1995-01-01

20

Comparison of three rapid methods, tributyrine, 4-methylumbelliferyl butyrate, and indoxyl acetate, for rapid identification of Moraxella catarrhalis.  

PubMed Central

Moraxella catarrhalis can easily be differentiated from other oxidase-positive, gram-negative cocci with tributyrine, 4-methylumbelliferyl butyrate, or indoxyl acetate. All M. catarrhalis give positive reactions, and all Neisseria spp. give negative reactions. The 4-methylumbelliferyl butyrate tube test and indoxyl acetate strip test provide same-day identification of M. catarrhalis isolates.

Speeleveld, E; Fossepre, J M; Gordts, B; Van Landuyt, H W

1994-01-01

21

Antigenic Heterogeneity and Molecular Analysis of CopB of Moraxella (Branhamella) catarrhalis  

Microsoft Academic Search

Outer membrane protein (OMP) CopB, an iron-repressible 81-kDa major OMP of Moraxella (Branhamella) catarrhalis has been a major focus of investigation. To assess CopB as a potential vaccine antigen, we elucidated the degree of antigenic and sequence heterogeneity in this protein among strains of M. catarrhalis. Two monoclonal antibodies, 1F5 and 2.9F, which bind to surface-exposed epitopes on CopB recognized

S. SETHI; J. M. SURFACE; T. F. MURPHY

1997-01-01

22

A 200 kDa protein is associated with haemagglutinating isolates of Moraxella (Branhamella) catarrhalis  

Microsoft Academic Search

Moraxella catarrhalis adheres to human erythrocytes by means of a proteinaceous, trypsin sensitive, heat modifiable haemagglutinin. A 200 kDa protein was found to be associated with haemagglutinating isolates of M. catarrhalis. This protein was present on all haemagglutinating isolates (n=17), but was absent on the non-haemagglutinating isolates (n=23) examined. This protein demonstrated heat-modifiable properties in sodium dodecyl sulfate and was

Margaret Fitzgerald; Riona Mulcahy; Susan Murphy; Conor Keane; Davis Coakley; Thomas Scott

1997-01-01

23

Immune Responses to Specific Antigens of Streptococcus pneumoniae and Moraxella catarrhalis in the Respiratory Tract  

Microsoft Academic Search

Streptococcus pneumoniae and Moraxella catarrhalis are two common respiratory pathogens, colonizing as many as 54 and 72% of children, respectively, by 1 year of age. The immune responses to surface protein A of S. pneumoniae (PspA) and the high-molecular-weight outer membrane protein of M. catarrhalis (UspA) in the sera of various age groups in the general population and in the

TAKAO SAMUKAWA; NOBORU YAMANAKA; SUSAN HOLLINGSHEAD; KARIN KLINGMAN; HOWARD FADEN

2000-01-01

24

Mapping of a Protective Epitope of the CopB Outer Membrane Protein of Moraxella catarrhalis  

Microsoft Academic Search

A monoclonal antibody (MAb) (MAb 10F3) directed against the CopB outer membrane protein of Moraxella catarrhalis previously was found to enhance pulmonary clearance of M. catarrhalis in an animal model (M. Helminen, I. Maciver, J. L. Latimer, L. D. Cope, G. H. McCracken, Jr., and E. J. Hansen, Infect. Immun. 61:2003-2010, 1993). In the present study, this same MAb was

CHRISTOPH AEBI; LESLIE D. COPE; JO L. LATIMER; SHARON E. THOMAS; CLIVE A. SLAUGHTER

25

Use of the Chinchilla Model for Nasopharyngeal Colonization To Study Gene Expression by Moraxella catarrhalis  

PubMed Central

Young adult chinchillas were atraumatically inoculated with Moraxella catarrhalis via the nasal route. Detailed histopathologic examination of nasopharyngeal tissues isolated from these M. catarrhalis-infected animals revealed the presence of significant inflammation within the epithelium. Absence of similar histopathologic findings in sham-inoculated animals confirmed that M. catarrhalis was exposed to significant host-derived factors in this environment. Twenty-four hours after inoculation, viable M. catarrhalis organisms were recovered from the nasal cavity and nasopharynx of the animals in numbers sufficient for DNA microarray analysis. More than 100 M. catarrhalis genes were upregulated in vivo, including open reading frames (ORFs) encoding proteins that are involved in a truncated denitrification pathway or in the oxidative stress response, as well as several putative transcriptional regulators. Additionally, 200 M. catarrhalis genes were found to be downregulated when this bacterium was introduced into the nasopharynx. These downregulated genes included ORFs encoding several well-characterized M. catarrhalis surface proteins including Hag, McaP, and MchA1. Real-time reverse transcriptase PCR (RT-PCR) was utilized as a stringent control to validate the results of in vivo gene expression patterns as measured by DNA microarray analysis. Inactivation of one of the genes (MC ORF 1550) that was upregulated in vivo resulted in a decrease in the ability of M. catarrhalis to survive in the chinchilla nasopharynx over a 3-day period. This is the first evaluation of global transcriptome expression by M. catarrhalis cells in vivo.

Hoopman, Todd C.; Liu, Wei; Joslin, Stephanie N.; Pybus, Christine; Sedillo, Jennifer L.; Labandeira-Rey, Maria; Laurence, Cassie A.; Wang, Wei; Richardson, James A.; Bakaletz, Lauren O.

2012-01-01

26

Middle ear mucin glycoprotein: Purification and interaction with nontypable Haemophilus influenzae and Moraxella catarrhalis  

Microsoft Academic Search

Nontypable Haemophilus influenzae and Moraxella catarrhalis are important pathogens in children and adults. The mechanisms of their adherence to the epithelial cell surface and colonization are not clear. For the pathogen to adhere to the epithelial cell, it must first attach to and penetrate the mucus barrier. Mucin glycoproteins of the mucus layer generally are thought to be involved in

MOLAKOLA S. REDDY; TIMOTHY F. MURPHY; HOWARD S. FADEN; JOEL M. BERNSTEIN

1997-01-01

27

Comparison of restriction enzymes for pulsed-field gel electrophoresis typing of Moraxella catarrhalis.  

PubMed

NotI, the most prevalent restriction enzyme used for typing Moraxella catarrhalis, failed to digest genomic DNA from respiratory samples. An improved pulsed-field gel electrophoresis (PFGE) methodology determined SpeI as the best choice for typing this bacterial species, with a good restriction of clinical samples and a good clustering correlation with NotI. PMID:23678064

Marti, Sara; Puig, Carmen; Domenech, Arnau; Liñares, Josefina; Ardanuy, Carmen

2013-07-01

28

Multiplex PCR assay that identifies the major lipooligosaccharide serotype expressed by Moraxella catarrhalis clinical isolates.  

PubMed

A heterologous cluster of glycosyltransferase genes was identified in the three Moraxella catarrhalis LOS serotype strains. Multiple PCR primers designed to this region amplified products that differentiate between the serotypes more rapidly and efficiently than previously described serological analyses. This assay will be valuable for clinical and research-based studies. PMID:16333114

Edwards, Katie J; Schwingel, Johanna M; Datta, Anup K; Campagnari, Anthony A

2005-12-01

29

Synthesis and Characterization of Lipooligosaccharide-Based Conjugates as Vaccine Candidates for Moraxella (Branhamella) catarrhalis  

Microsoft Academic Search

Moraxella (Branhamella) catarrhalis is an important cause of otitis media and sinusitis in children and of lower respiratory tract infections in adults. Lipooligosaccharide (LOS) is a major surface antigen of the bacterium and elicits bactericidal antibodies. Treatment of the LOS from strain ATCC 25238 with anhydrous hydrazine reduced its toxicity 20,000-fold, as assayed in the Limulus amebocyte lysate (LAL) test.

XIN-XING GU; JING CHEN; STEPHEN J. BARENKAMP; JOHN B. ROBBINS; CHAO-MING TSAI; DAVID J. LIM; JAMES BATTEY

1998-01-01

30

Comparison of Restriction Enzymes for Pulsed-Field Gel Electrophoresis Typing of Moraxella catarrhalis  

PubMed Central

NotI, the most prevalent restriction enzyme used for typing Moraxella catarrhalis, failed to digest genomic DNA from respiratory samples. An improved pulsed-field gel electrophoresis (PFGE) methodology determined SpeI as the best choice for typing this bacterial species, with a good restriction of clinical samples and a good clustering correlation with NotI.

Puig, Carmen; Domenech, Arnau; Linares, Josefina; Ardanuy, Carmen

2013-01-01

31

Moraxella catarrhalis expresses a cardiolipin synthase that impacts adherence to human epithelial cells.  

PubMed

The major phospholipid constituents of Moraxella catarrhalis membranes are phosphatidylglycerol, phosphatidylethanolamine, and cardiolipin (CL). However, very little is known regarding the synthesis and function of these phospholipids in M. catarrhalis. In this study, we discovered that M. catarrhalis expresses a cardiolipin synthase (CLS), termed MclS, that is responsible for the synthesis of CL within the bacterium. The nucleotide sequence of mclS is highly conserved among M. catarrhalis isolates and is predicted to encode a protein with significant amino acid similarity to the recently characterized YmdC/ClsC protein of Escherichia coli. Isogenic mclS mutant strains were generated in M. catarrhalis isolates O35E, O12E, and McGHS1 and contained no observable levels of CL. Site-directed mutagenesis of a highly conserved HKD motif of MclS also resulted in a CL-deficient strain. Moraxella catarrhalis, which depends on adherence to epithelial cells for colonization of the human host, displays significantly reduced levels of adherence to HEp-2 and A549 cell lines in the mclS mutant strains compared to wild-type bacteria. The reduction in adherence appears to be attributed to the absence of CL. These findings mark the first instance in which a CLS has been related to a virulence-associated trait. PMID:24142255

Buskirk, Sean W; Lafontaine, Eric R

2014-01-01

32

Moraxella catarrhalis Expresses a Cardiolipin Synthase That Impacts Adherence to Human Epithelial Cells  

PubMed Central

The major phospholipid constituents of Moraxella catarrhalis membranes are phosphatidylglycerol, phosphatidylethanolamine, and cardiolipin (CL). However, very little is known regarding the synthesis and function of these phospholipids in M. catarrhalis. In this study, we discovered that M. catarrhalis expresses a cardiolipin synthase (CLS), termed MclS, that is responsible for the synthesis of CL within the bacterium. The nucleotide sequence of mclS is highly conserved among M. catarrhalis isolates and is predicted to encode a protein with significant amino acid similarity to the recently characterized YmdC/ClsC protein of Escherichia coli. Isogenic mclS mutant strains were generated in M. catarrhalis isolates O35E, O12E, and McGHS1 and contained no observable levels of CL. Site-directed mutagenesis of a highly conserved HKD motif of MclS also resulted in a CL-deficient strain. Moraxella catarrhalis, which depends on adherence to epithelial cells for colonization of the human host, displays significantly reduced levels of adherence to HEp-2 and A549 cell lines in the mclS mutant strains compared to wild-type bacteria. The reduction in adherence appears to be attributed to the absence of CL. These findings mark the first instance in which a CLS has been related to a virulence-associated trait.

Buskirk, Sean W.

2014-01-01

33

Comparative analyses of the Moraxella catarrhalis type-IV pilus structural subunit PilA.  

PubMed

Moraxella catarrhalis is a Gram-negative aerobic diplococcus that is a mucosal pathogen of the upper and lower respiratory tracts in humans. In order to colonize the human host and establish an infection, M. catarrhalis must be able to effectively attach to the respiratory mucosal epithelia. Although little is known about M. catarrhalis pathogenesis, our laboratory has previously shown that expression of type IV pili (TFP) contributes to mucosal colonization. TFP are filamentous surface appendages primarily composed of a single protein subunit termed pilin, which is encoded by pilA in M. catarrhalis. These surface structures play a crucial role in the initiation of disease by a wide range of pathogenic bacteria. Our studies also indicate that unlike the pilin of the pathogenic Neisseria species, which exhibit both phase and antigenic variation, the pilin subunit of M. catarrhalis appears to be more highly conserved as there are no major pilin variants produced by a single strain and only two major PilA antigenic variants, termed clade 1 and clade 2, have been observed between strains. Moreover, we have determined that these highly conserved bacterial surface structures are expressed by all M. catarrhalis clinical isolates evaluated. Therapeutic or vaccine-based interventions that prevent or diminish nasopharyngeal colonization will likely decrease acute and recurrent M. catarrhalis infections in prone populations. Thus, our data indicate that additional studies aimed at elucidating the role of PilA in the pathogenesis and host response to M. catarrhalis infections are warranted. PMID:21256201

Luke-Marshall, Nicole R; Sauberan, Shauna L; Campagnari, Anthony A

2011-05-15

34

Moraxella catarrhalis uses a twin-arginine translocation system to secrete the ?-lactamase BRO-2  

PubMed Central

Background Moraxella catarrhalis is a human-specific gram-negative bacterium readily isolated from the respiratory tract of healthy individuals. The organism also causes significant health problems, including 15-20% of otitis media cases in children and ~10% of respiratory infections in adults with chronic obstructive pulmonary disease. The lack of an efficacious vaccine, the rapid emergence of antibiotic resistance in clinical isolates, and high carriage rates reported in children are cause for concern. Virtually all Moraxella catarrhalis isolates are resistant to ?-lactam antibiotics, which are generally the first antibiotics prescribed to treat otitis media in children. The enzymes responsible for this resistance, BRO-1 and BRO-2, are lipoproteins and the mechanism by which they are secreted to the periplasm of M. catarrhalis cells has not been described. Results Comparative genomic analyses identified M. catarrhalis gene products resembling the TatA, TatB, and TatC proteins of the well-characterized Twin Arginine Translocation (TAT) secretory apparatus. Mutations in the M. catarrhalis tatA, tatB and tatC genes revealed that the proteins are necessary for optimal growth and resistance to ?-lactams. Site-directed mutagenesis was used to replace highly-conserved twin arginine residues in the predicted signal sequence of M. catarrhalis strain O35E BRO-2, which abolished resistance to the ?-lactam antibiotic carbanecillin. Conclusions Moraxella catarrhalis possesses a TAT secretory apparatus, which plays a key role in growth of the organism and is necessary for secretion of BRO-2 into the periplasm where the enzyme can protect the peptidoglycan cell wall from the antimicrobial activity of ?-lactam antibiotics.

2013-01-01

35

Respiratory Syncytial Virus Promotes Moraxella catarrhalis-Induced Ascending Experimental Otitis Media  

PubMed Central

Otitis media (OM) is a polymicrobial disease wherein prior or concurrent infection with an upper respiratory tract virus plays an essential role, predisposing the middle ear to bacterial invasion. In episodes of acute bacterial OM, respiratory syncytial virus (RSV) is the most commonly isolated virus and thus serves as an important co-pathogen. Of the predominant bacterial agents of OM, the pathogenesis of disease due to Moraxella catarrhalis is the least well understood. Rigorous study of M. catarrhalis in the context of OM has been significantly hindered by lack of an animal model. To bridge this gap, we assessed whether co-infection of chinchillas with M. catarrhalis and RSV would facilitate ascension of M. catarrhalis from the nasopharynx into the middle ear. Chinchillas were challenged intranasally with M. catarrhalis followed 48 hours later by intranasal challenge with RSV. Within 7 days, 100% of nasopharynges were colonized with M. catarrhalis and homogenates of middle ear mucosa were also culture-positive. Moreover, within the middle ear space, the mucosa exhibited hemorrhagic foci, and a small volume of serosanguinous effusion was present in one of six ears. To improve upon this model, and based on epidemiologic data, nontypeable Haemophilus influenzae (NTHI) was included as an additional bacterial co-pathogen via intranasal administration four days before M. catarrhalis challenge. With this latter protocol, M. catarrhalis was cultured from the nasopharynx and middle ear homogenates of a maximum of 88% and 79% animals, respectively, for up to 17 days after intranasal challenge with M. catarrhalis. Additionally, hemorrhagic foci were observed in 79% of middle ears upon sacrifice. Thus, these data demonstrated that co-infection with RSV and NTHI predisposed to M. catarrhalis-induced ascending experimental OM. This model can be used both in studies of pathogenesis as well as to investigate strategies to prevent or treat OM due to M. catarrhalis.

Brockson, M. Elizabeth; Novotny, Laura A.; Jurcisek, Joseph A.; McGillivary, Glen; Bowers, Martha R.; Bakaletz, Lauren O.

2012-01-01

36

Unveiling electrotransformation of Moraxella catarrhalis as a process of natural transformation.  

PubMed

The human respiratory tract pathogen Moraxella catarrhalis is a naturally competent microorganism. However, electrotransformation has long been used to introduce foreign DNA into this organism. This study demonstrated that electrotransformants obtained with linear or circular nonreplicating plasmid DNA originated exclusively from natural transformation processes taking place during the recovery phase after the application of current. Only replicating plasmid DNA could be introduced into M. catarrhalis by electrotransformation, in a type IV pilus-independent manner. Electrotransformation with homologous genomic DNA indicated that restriction of double-stranded DNA was independent of type III restriction-methylation systems. Nontransformability of M. catarrhalis by electrotransformation was observed using double- as well as single-stranded DNA. In addition, the study showed that natural competence is a very constant feature of M. catarrhalis. PMID:16907741

Meier, Patricia Stutzmann; Troller, Rolf; Heiniger, Nadja; Hays, John P; van Belkum, Alex; Aebi, Christoph

2006-09-01

37

Development of a LacZ-based transcriptional reporter system for use with Moraxella catarrhalis.  

PubMed

The lack of a transcriptional reporter system for use in Moraxella catarrhalis has hindered studies of gene regulation in this pathogen. PCR and recombinant DNA methods were used to insert a multicloning site (MCS) and promoterless full-length Escherichia coli lacZ gene, flanked by transcriptional terminators both immediately upstream and downstream, into the M. catarrhalis recombinant plasmid pWW115. Insertion into the MCS in the newly constructed plasmid pASE222 of M. catarrhalis promoter regions controlled by either a repressor (i.e., NsrR) or activator (i.e., PhoB) yielded transcriptional fusion constructs that were appropriately responsive to signal inputs dependent on the host strain genotype, as measured quantitatively by means of a Miller ?-galactosidase assay. The transcriptional reporter plasmid pASE222 should prove to be a useful tool for rapid screening of factors affecting gene expression in M. catarrhalis. PMID:23219721

Evans, Amanda S; Pybus, Christine; Hansen, Eric J

2013-03-01

38

Development of a LacZ-Based Transcriptional Reporter System for Use with Moraxella catarrhalis  

PubMed Central

The lack of a transcriptional reporter system for use in Moraxella catarrhalis has hindered studies of gene regulation in this pathogen. PCR and recombinant DNA methods were used to insert a multicloning site (MCS) and promoterless full-length E. coli lacZ gene, flanked by transcriptional terminators both immediately upstream and downstream, into the M. catarrhalis recombinant plasmid pWW115. Insertion into the MCS in the newly constructed plasmid pASE222 of M. catarrhalis promoter regions controlled by either a repressor (i.e., NsrR) or activator (i.e., PhoB) yielded transcriptional fusion constructs that were appropriately responsive to signal inputs dependent on the host strain genotype, as measured quantitatively by means of a Miller ?-galactosidase assay. The transcriptional reporter plasmid pASE222 should prove to be a useful tool for rapid screening of factors affecting gene expression in M. catarrhalis.

Evans, Amanda S.; Pybus, Christine; Hansen, Eric J.

2012-01-01

39

The PROTEKT surveillance study: antimicrobial susceptibility of Haemophilus influenzae and Moraxella catarrhalis from community-acquired respiratory tract infections  

Microsoft Academic Search

This paper presents data relating to Haemophilus influenzae and Moraxella catarrhalis from PROTEKT (1999-2000), a surveillance study that examined the susceptibility of respiratory patho- gens to current and new antibacterials. ?-Lactamase production is the principal mechanism of resistance to ampicillin and other ?-lactam antibacterials in H. influenzae and M. catarrhalis. The PROTEKT study showed that globally, the prevalence of ?-lactamase

Daryl Hoban; David Felmingham

2002-01-01

40

Inactivation of the Moraxella catarrhalis 7169 Ferric Uptake Regulator Increases Susceptibility to the Bactericidal Activity of Normal Human Sera  

Microsoft Academic Search

Moraxella catarrhalis is a strict human pathogen and a significant cause of respiratory disease and otitis media. In direct response to these infections, research efforts have focused primarily on the identification of potential vaccine targets. The general biology of M. catarrhalis, however, including the mechanisms utilized to survive in the human host, remains poorly understood. Previous work has demonstrated that

Kristin Furano; Anthony A. Campagnari

2003-01-01

41

A 1997–1998 national surveillance study: Moraxella catarrhalis and Haemophilus influenzae antimicrobial resistance in 34 US institutions  

Microsoft Academic Search

From November 1, 1997 to April 30, 1998, 726 Moraxella catarrhalis isolates and 1529 Haemophilus influenzae isolates were obtained from 34 medical centres throughout the United States. Rates of ?-lactamase production were 94.6% among M. catarrhalis and 31.1% among H. influenzae strains. Susceptibility rates of M. catarrhalis isolates to selected antimicrobial agents were greater than 99% for amoxycillin-clavulanate, cefixime, cefpodoxime,

Sandra S. Richter; Angela B. Brueggemann; Holly K. Huynh; Paul R. Rhomberg; Elizabeth M. Wingert; Robert Flamm; Gary V. Doern

1999-01-01

42

Moraxella catarrhalis induces ERK and NF B-dependent COX2 and prostaglandin E2 in lung epithelium  

Microsoft Academic Search

Moraxella catarrhalis is a major cause of infectious exacerbations of chronic obstructive lung disease. Cyclooxygenase (COX)-derived prostaglandins, such as prostaglandin E2 (PGE2), are considered to be important regulators of lung function. The present authors tested the hypothesis that M. catarrhalis induces COX-2-dependent PGE2 production in pulmonary epithelial cells. In the present study, the authors demonstrate that M. catarrhalis specifically induces

P. D. N'Guessan; B. Temmesfeld-Wollbruck; J. Zahlten; J. Eitel; S. Zabel; B. Schmeck; B. Opitz; S. Hippenstiel; N. Suttorp; H. Slevogt

2007-01-01

43

The Moraxella catarrhalis nitric oxide reductase is essential for nitric oxide detoxification.  

PubMed

Moraxella catarrhalis is a Gram-negative obligate aerobe that is an important cause of human respiratory tract infections. The M. catarrhalis genome encodes a predicted truncated denitrification pathway that reduces nitrate to nitrous oxide. We have previously shown that expression of both the M. catarrhalis aniA (encoding a nitrite reductase) and norB (encoding a putative nitric oxide reductase) genes is repressed by the transcriptional regulator NsrR under aerobic conditions and that M. catarrhalis O35E nsrR mutants are unable to grow in the presence of low concentrations of nitrite (W. Wang, et al., J. Bacteriol. 190:7762-7772, 2008). In this study, we constructed an M. catarrhalis norB mutant and showed that planktonic growth of this mutant is inhibited by low levels of nitrite, whether or not an nsrR mutation is present. To determine the importance of NorB in this truncated denitrification pathway, we analyzed the metabolism of nitrogen oxides by norB, aniA norB, and nsrR norB mutants. We found that norB mutants are unable to reduce nitric oxide and produce little or no nitrous oxide from nitrite. Furthermore, nitric oxide produced from nitrite by the AniA protein is bactericidal for a Moraxella catarrhalis O35E norB mutant but not for wild-type O35E bacteria under aerobic growth conditions in vitro, suggesting that nitric oxide catabolism in M. catarrhalis is accomplished primarily by the norB gene product. Measurement of bacterial protein S-nitrosylation directly implicates nitrosative stress resulting from AniA-dependent nitric oxide formation as a cause of the growth inhibition of norB and nsrR mutants by nitrite. PMID:21441505

Wang, Wei; Kinkel, Traci; Martens-Habbena, Willm; Stahl, David A; Fang, Ferric C; Hansen, Eric J

2011-06-01

44

Isolation and Characterization of Two Proteins from Moraxella catarrhalis That Bear a Common Epitope  

Microsoft Academic Search

The UspA1 and UspA2 proteins of Moraxella catarrhalis are potential vaccine candidates for preventing disease caused by this organism. We have characterized both proteins and evaluated their vaccine potential using both in vitro and in vivo assays. Both proteins were purified from the O35E isolate by Triton X-100 extraction, followed by ion-exchange and hydroxyapatite chromatography. Analysis of the sequences of

JOHN C. MCMICHAEL; MICHAEL J. FISKE; ROSS A. FREDENBURG; DEB N. CHAKRAVARTI; KARL R. VANDERMEID; VICKI BARNIAK; JEFFREY CAPLAN; ERIC BORTELL; STEVEN BAKER; RASAPPA ARUMUGHAM; DEXIANG CHEN

1998-01-01

45

Functional Characteristics of a Protective Monoclonal Antibody against Serotype A and C Lipooligosaccharides from Moraxella catarrhalis  

Microsoft Academic Search

A monoclonal antibody (MAb), designated MAb 8E7 (immunoglobulin G3), specific for Moraxella catarrhalis lipooligosaccharide (LOS) was evaluated for its functional activity in vitro and in a mouse model of coloni- zation. Enzyme-linked immunosorbent assay (ELISA) demonstrated that the MAb 8E7 could be prepared to a high titer against LOS of the homologous strain 035E, and that it had bactericidal activity.

WEI-GANG HU; JING CHEN; JOHN C. MCMICHAEL; XIN-XING GU

2001-01-01

46

Structural studies of the O-antigen oligosaccharides from two strains of Moraxella catarrhalis serotype C  

Microsoft Academic Search

The oligosaccharide parts from Moraxella (Branhamella) catarrhalis serotype C lipooligosaccharides were isolated by mild acid hydrolysis followed by gel permeation chromatography. Four different oligosaccharides could be identified from strain RS26 and two from strain RS10. The structures of the O-oligosaccharides were established by methylation analyses, mass spectrometry, and NMR spectrscopy. It is concluded that the oligosaccharide O-antigens from RS26 are

Per Edebrink; Per-Erik Jansson; M. Mahbubur Rahman; Göran Widmalm; Tord Holme; Motiur Rahman

1995-01-01

47

Use of molecular methods to characterize Moraxella catarrhalis strains in a suspected outbreak of nosocomial infection  

Microsoft Academic Search

Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of whole cell protein, immunoblotting with normal human serum and restriction endonuclease analysis usingTaq I enzyme were applied to 38 clinically significant isolates ofMoraxella (Branhamella) catarrhalis obtained during a suspected outbreak of nosocomial infection. Each of 18 strains had individual profiles by at least two of the three methods (unique strains). The remaining 20 strains

M. G. Morgan; H. McKenzie; M. C. Enright; M. Bain; F. X. S. Emmanuel

1992-01-01

48

Nutrient agar with sodium chloride supplementation for presumptive detection of Moraxella catarrhalis in clinical specimens.  

PubMed

We previously reported that Nissui nutrient agar (N medium) promoted the growth of Moraxella catarrhalis but not commensal Neisseria spp. In the present study, we examined which constituent of N medium was responsible for the selective growth of M. catarrhalis using 209 M. catarrhalis and 100 commensal Neisseria spp. clinical strains. We found that peptone, but not meat extract or agar of N medium, had growth-promoting or growth-inhibiting ability with respect to M. catarrhalis and commensal Neisseria spp. Thus, we investigated the amino acid content of N peptone and found it had higher concentrations of amino acids than other commercial peptone products. On varying the sodium chloride concentration of reconstituted N medium, we noted that the concentration was an important factor in bacterial growth differences. Varying the sodium chloride concentration of other commercial nutrient agars achieved similar results to those for N medium. This is, to our knowledge, the first study observing that sodium chloride concentration is responsible for difference in growth between the two organisms. We also successfully isolated colonies of M. catarrhalis from respiratory specimens on N medium, whereas the growth of commensal Neisseria spp. was inhibited, and by adding bovine hematin and ?-NAD we were able to isolate Haemophilus influenzae colonies as efficiently as with a chocolate agar. In conclusion, nutrient agar can be used as a medium for the preferential isolation of M. catarrhalis from upper respiratory tract specimens. PMID:22350402

Nishiyama, Hiroyuki; Saito, Ryoichi; Chida, Toshio; Sano, Kazumitsu; Tsuchiya, Tatsuyuki; Okamura, Noboru

2012-04-01

49

Rapid typing of Moraxella catarrhalis subpopulations based on outer membrane proteins using mass spectrometry.  

PubMed

Moraxella catarrhalis is a major mucosal pathogen of the human respiratory tract both in children and in adults. Two subpopulations of this organism have been described that differ in 16S rRNA gene sequence and virulence traits. Three 16S rRNA types have been defined. 2-DE followed by protein identification by MS revealed significant differences in the outer membrane protein (OMP) patterns of each M. catarrhalis 16S rRNA type. Approximately 130 features were detected on the 2-DE map of each M. catarrhalis 16S rRNA type. However, only 50 features were expressed by all strains. Furthermore, direct profiling of isolated OMP using MALDI-TOF MS resulted in a characteristic spectral fingerprint for each 16S rRNA type. Fingerprints remained identical when intact cells instead of isolated OMP were analyzed. This finding suggests that the source of desorbed ions is the outer membrane. Based on the fingerprint we were able to assign 18 well-characterized clinical M. catarrhalis isolates to the correct subpopulation. Therefore, MALDI-TOF of intact M. catarrhalis provides a rapid and robust tool for M. catarrhalis strain typing that could be applied in epidemiological studies. PMID:16317771

Schaller, André; Troller, Rolf; Molina, Daniel; Gallati, Sabina; Aebi, Christoph; Stutzmann Meier, Patricia

2006-01-01

50

Asialo-GM1 and asialo-GM2 are putative adhesion molecules for Moraxella catarrhalis.  

PubMed

Moraxella catarrhalis is an important pathogen of respiratory and middle ear infections. We previously reported that the attachment of M. catarrhalis to pharyngeal epithelial cells is mediated by ganglioside M2 (GM2). Several sets of adhesins or receptors are involved in such attachment process. In this study, we used the same strains and similar bacterial culture conditions as those in our previous study, and demonstrated by thin layer chromatography that M. catarrhalis can also bind to asialo-GM1 (Gg4Cer) and asialo-GM2 (Gg3Cer). GalNAcbeta1-->4Galbeta1 is a common sequence in both Gg4Cer and Gg3Cer, and in many respiratory bacteria, this sequence acts as a receptor for attachment to host cells. Treatment of human pharyngeal epithelial cells with anti-GM2 and anti-Gg4Cer antibodies significantly decreased attachment of M. catarrhalis to these cells; however, treatment with anti-Gg3Cer antibody did not decrease M. catarrhalis attachment. Immunofluorescence microscopy revealed that human pharyngeal epithelial cells are positive for GM2 and Gg4Cer, but not for Gg3Cer. Our results indicate that Gg4Cer on human pharyngeal epithelial cells, and Gg3Cer,possibly on other cells, could serve as molecules for attachment of M. catarrhalis. PMID:12137200

Ahmed, Kamruddin; Suzuki, Yasuo; Miyamoto, Daisei; Nagatake, Tsuyoshi

2002-05-01

51

Evaluation of the BactiCard Neisseria for identification of pathogenic Neisseria species and Moraxella catarrhalis.  

PubMed

The BactiCard Neisseria (Remel, USA) is a chromogenic enzyme substrate system for identifying Neisseria gonorrhoeae, Neisseria meningitidis, Neisseria lactamica, and Moraxella catarrhalis. The identification system consists of a card with four test circles impregnated with chromogenic substrates for indoxyl butyrate esterase (IB), prolyl aminopeptidase (PRO), gamma-glutamyl aminopeptidase (GLUT), and ss-galactosidase (BGAL). These substrates permit the identification of Moraxella catarrhalis, Neisseria gonorrhoeae, Neisseria meningitidis, and Neisseria lactamica, respectively. After hydration of the circles with buffer, colonies from growth on selective media or a subculture are applied to the four circles. IB and BGAL reactions are read for a blue-green color after 2 and 15 min, respectively. PRO and GLUT reactions are read at 15 min for a red color after addition of a developer reagent. Identifications obtained with the BactiCard Neisseria were compared with those obtained using conventional procedures for 558 isolates in a blinded fashion. The BactiCard Neisseria identified 100% of 254 Neisseria gonorrhoeae, 100% of 125 Neisseria meningitidis, 53 (98.2%) of 54 Neisseria lactamica, and 123 (98.4%) of 125 Moraxella catarrhalis isolates. The BactiCard Neisseria is an accurate and rapid system for identification of these microorganisms in the clinical laboratory. PMID:12525923

Janda, W M; Montero, M C; Wilcoski, L M

2002-12-01

52

Comprehensive Antigen Screening Identifies Moraxella catarrhalis Proteins That Induce Protection in a Mouse Pulmonary Clearance Model  

PubMed Central

Moraxella catarrhalis is one of the three most common causative bacterial pathogens of otitis media, however no effective vaccine against M. catarrhalis has been developed so far. To identify M. catarrhalis vaccine candidate antigens, we used carefully selected sera from children with otitis media and healthy individuals to screen small-fragment genomic libraries that are expressed to display frame-selected peptides on a bacterial cell surface. This ANTIGENome technology led to the identification of 214 antigens, 23 of which were selected by in vitro or in vivo studies for additional characterization. Eight of the 23 candidates were tested in a Moraxella mouse pulmonary clearance model, and 3 of these antigens induced significantly faster bacterial clearance compared to adjuvant or to the previously characterized antigen OmpCD. The most significant protection data were obtained with the antigen MCR_1416 (Msp22), which was further investigated for its biological function by in vitro studies suggesting that Msp22 is a heme binding protein. This study comprises one of the most exhaustive studies to identify potential vaccine candidate antigens against the bacterial pathogen M. catarrhalis.

Verhaegh, Suzanne J. C.; Niebisch, Axel; Hanner, Markus; Selak, Sanja; Schuler, Wolfgang; Morfeldt, Eva; Hellberg, Christel; Nagy, Eszter; Lundberg, Urban; Hays, John P.; Meinke, Andreas; Henriques-Normark, Birgitta

2013-01-01

53

Role of the Zinc Uptake ABC Transporter of Moraxella catarrhalis in Persistence in the Respiratory Tract  

PubMed Central

Moraxella catarrhalis is a human respiratory tract pathogen that causes otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease. We have identified and characterized a zinc uptake ABC transporter that is present in all strains of M. catarrhalis tested. A mutant in which the znu gene cluster is knocked out shows markedly impaired growth compared to the wild type in medium that contains trace zinc; growth is restored to wild-type levels by supplementing medium with zinc but not with other divalent cations. Thermal-shift assays showed that the purified recombinant substrate binding protein ZnuA binds zinc but does not bind other divalent cations. Invasion assays with human respiratory epithelial cells demonstrated that the zinc ABC transporter of M. catarrhalis is critical for invasion of respiratory epithelial cells, an observation that is especially relevant because an intracellular reservoir of M. catarrhalis is present in the human respiratory tract and this reservoir is important for persistence. The znu knockout mutant showed marked impairment in its capacity to persist in the respiratory tract compared to the wild type in a mouse pulmonary clearance model. We conclude that the zinc uptake ABC transporter mediates uptake of zinc in environments with very low zinc concentrations and is critical for full virulence of M. catarrhalis in the respiratory tract in facilitating intracellular invasion of epithelial cells and persistence in the respiratory tract.

Brauer, Aimee L.; Kirkham, Charmaine; Johnson, Antoinette; Koszelak-Rosenblum, Mary; Malkowski, Michael G.

2013-01-01

54

Role of the zinc uptake ABC transporter of Moraxella catarrhalis in persistence in the respiratory tract.  

PubMed

Moraxella catarrhalis is a human respiratory tract pathogen that causes otitis media in children and lower respiratory tract infections in adults with chronic obstructive pulmonary disease. We have identified and characterized a zinc uptake ABC transporter that is present in all strains of M. catarrhalis tested. A mutant in which the znu gene cluster is knocked out shows markedly impaired growth compared to the wild type in medium that contains trace zinc; growth is restored to wild-type levels by supplementing medium with zinc but not with other divalent cations. Thermal-shift assays showed that the purified recombinant substrate binding protein ZnuA binds zinc but does not bind other divalent cations. Invasion assays with human respiratory epithelial cells demonstrated that the zinc ABC transporter of M. catarrhalis is critical for invasion of respiratory epithelial cells, an observation that is especially relevant because an intracellular reservoir of M. catarrhalis is present in the human respiratory tract and this reservoir is important for persistence. The znu knockout mutant showed marked impairment in its capacity to persist in the respiratory tract compared to the wild type in a mouse pulmonary clearance model. We conclude that the zinc uptake ABC transporter mediates uptake of zinc in environments with very low zinc concentrations and is critical for full virulence of M. catarrhalis in the respiratory tract in facilitating intracellular invasion of epithelial cells and persistence in the respiratory tract. PMID:23817618

Murphy, Timothy F; Brauer, Aimee L; Kirkham, Charmaine; Johnson, Antoinette; Koszelak-Rosenblum, Mary; Malkowski, Michael G

2013-09-01

55

Passive smoking and nasopharyngeal colonization by Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in daycare children.  

PubMed

Exposure to tobacco smoke may be associated with higher risk of nasopharyngeal colonization and infection by Streptococcus pneumoniae (SP), Haemophilus influenzae (HI), and Moraxella catarrhalis (MC). This study was done to determine the influence of passive smoking on S. pneumoniae, H. influenzae, and M. catarrhalis colonization rates among children. This is a prospective cross-sectional study. Tertiary referral centers with accredited otorhinolaryngology-head and neck surgery and Microbiology Departments. In this cross-sectional study, 2-6 years old children in 10 randomly selected day-care centers in northeast of Iran (Mashad) were studied. Smoking exposure and medical history were recorded. Carriage rates for aforementioned bacteria were analyzed on the basis of smoking exposure. 1,125 children (Female/Male: 597/528) with the mean age of 5.05 ± 0.98 years were studied. Carriage rates of S. pneumoniae, H. influenzae and M. catarrhalis among children were 10.1, 8.8 and 6.7%, respectively. Mixed colonization was found in 2.7%. There was a significant difference in carriage rates between children who live in smoking families compare to those with nonsmoking families for M. catarrhalis (P = 0.001) but not for S. pneumoniae, and H. influenza (P = 0.798 and P = 0.117, respectively). It seems exposure to tobacco smoke is associated with increased carriage rate of M. catarrhalis in day-care children. PMID:22033573

Bakhshaee, Mehdi; Naderi, Hamid Reza; Ghazvini, Kiarash; Sotoudeh, Kambiz; Amali, Amin; Ashtiani, Sara Jafari

2012-04-01

56

Characterization and Evaluation of the Moraxella catarrhalis Oligopeptide Permease A as a Mucosal Vaccine Antigen?  

PubMed Central

Moraxella catarrhalis is a common cause of otitis media in children and of lower respiratory tract infections in adults with chronic obstructive pulmonary disease; therefore, these two groups would benefit from a vaccine to prevent M. catarrhalis infections. A genome mining approach for vaccine antigens identified oligopeptide permease protein A (OppA), an oligopeptide binding protein of an apparent oligopeptide transport system. Analysis of the oppA gene by PCR and sequence analysis revealed that OppA is highly conserved among clinical isolates of M. catarrhalis. Recombinant OppA was expressed as a lipoprotein and purified, and an oppA knockout mutant was constructed. Antiserum raised to recombinant purified OppA recognized epitopes on the bacterial surface of the wild type but not the OppA knockout mutant. Antibodies raised to purified recombinant OppA recognized native OppA in multiple strains. Intranasal immunization of mice induced systemic and mucosal antibodies to OppA and resulted in enhanced clearance of M. catarrhalis in a mouse pulmonary clearance model. OppA is a highly conserved, immunogenic protein that expresses epitopes on the bacterial surface and that induces potentially protective immune responses in a mouse model. OppA should be evaluated further as a vaccine antigen for M. catarrhalis.

Yang, Min; Johnson, Antoinette; Murphy, Timothy F.

2011-01-01

57

Characterization of the molecular interplay between Moraxella catarrhalis and human respiratory tract epithelial cells.  

PubMed

Moraxella catarrhalis is a mucosal pathogen that causes childhood otitis media and exacerbations of chronic obstructive pulmonary disease in adults. During the course of infection, M. catarrhalis needs to adhere to epithelial cells of different host niches such as the nasopharynx and lungs, and consequently, efficient adhesion to epithelial cells is considered an important virulence trait of M. catarrhalis. By using Tn-seq, a genome-wide negative selection screenings technology, we identified 15 genes potentially required for adherence of M. catarrhalis BBH18 to pharyngeal epithelial Detroit 562 and lung epithelial A549 cells. Validation with directed deletion mutants confirmed the importance of aroA (3-phosphoshikimate 1-carboxyvinyl-transferase), ecnAB (entericidin EcnAB), lgt1 (glucosyltransferase), and MCR_1483 (outer membrane lipoprotein) for cellular adherence, with ?MCR_1483 being most severely attenuated in adherence to both cell lines. Expression profiling of M. catarrhalis BBH18 during adherence to Detroit 562 cells showed increased expression of 34 genes in cell-attached versus planktonic bacteria, among which ABC transporters for molybdate and sulfate, while reduced expression of 16 genes was observed. Notably, neither the newly identified genes affecting adhesion nor known adhesion genes were differentially expressed during adhesion, but appeared to be constitutively expressed at a high level. Profiling of the transcriptional response of Detroit 562 cells upon adherence of M. catarrhalis BBH18 showed induction of a panel of pro-inflammatory genes as well as genes involved in the prevention of damage of the epithelial barrier. In conclusion, this study provides new insight into the molecular interplay between M. catarrhalis and host epithelial cells during the process of adherence. PMID:23936538

de Vries, Stefan P W; Eleveld, Marc J; Hermans, Peter W M; Bootsma, Hester J

2013-01-01

58

Fluoroquinolone-resistant Moraxella catarrhalis in a patient with pneumonia: report from the SENTRY antimicrobial surveillance program (1998)  

Microsoft Academic Search

Fluoroquinolone resistance in Moraxella catarrhalis isolates has been quite rare. This report presents a case history of a 22-year-old man with compromised immune status and severe pneumonia caused by M. catarrhalis. The organism was markedly resistant (MICs, 1.5–>32 ?g\\/mL) to several marketed fluoroquinolones including the agent (levofloxacin) used for concurrent and prior therapy. The emergence of this problematic strain seems

Joseph R DiPersio; Ronald N Jones; Timothy Barrett; Gary V Doern; Michael A Pfaller

1998-01-01

59

Enhancement of Clearance of Bacteria from Murine Lungs by Immunization with Detoxified Lipooligosaccharide from Moraxella catarrhalis Conjugated to Proteins  

Microsoft Academic Search

Moraxella catarrhalis strain 25238 detoxified lipooligosaccharide (dLOS)-protein conjugates induced a sig- nificant rise of bactericidal anti-LOS antibodies in animals. This study reports the effect of active or passive immunization with the conjugates or their antiserum on pulmonary clearance of M. catarrhalis in an aerosol challenge mouse model. Mice were injected subcutaneously with dLOS-tetanus toxoid (dLOS-TT), dLOS- high-molecular-weight proteins (dLOS-HMP) from

WEI-GANG HU; JING CHEN; JAMES F. BATTEY; XIN-XING GU

2000-01-01

60

Binding of Vitronectin by the Moraxella catarrhalis UspA2 Protein Interferes with Late Stages of the Complement Cascade  

Microsoft Academic Search

Many Moraxella catarrhalis strains are resistant to the bactericidal activity of normal human serum (NHS). The UspA2 protein of the serum-resistant strain O35E has previously been shown to be directly involved in conferring serum resistance on this strain. Testing of 11 additional serum-resistant M. catarrhalis wild-type isolates and their uspA1 and uspA2 mutants showed that the uspA1 mutants of all

Ahmed S. Attia; Sanjay Ram; Peter A. Rice; Eric J. Hansen

2006-01-01

61

Identification of Gene Products Involved in the Oxidative Stress Response of Moraxella catarrhalis ? †  

PubMed Central

Moraxella catarrhalis is subjected to oxidative stress from both internal and environmental sources. A previous study (C. D. Pericone, K. Overweg, P. W. Hermans, and J. N. Weiser, Infect. Immun. 68:3990-3997, 2000) indicated that a wild-type strain of M. catarrhalis was very resistant to killing by exogenous hydrogen peroxide (H2O2). The gene encoding OxyR, a LysR family transcriptional regulator, was identified and inactivated in M. catarrhalis strain O35E, resulting in an increase in sensitivity to killing by H2O2 in disk diffusion assays and a concomitant aerobic serial dilution effect. Genes encoding a predicted catalase (KatA) and an alkyl hydroperoxidase (AhpCF) showed dose-dependent upregulation in wild-type cells exposed to H2O2. DNA microarray and real-time reverse transcription-PCR (RT-PCR) analyses identified M. catarrhalis genes whose expression was affected by oxidative stress in an OxyR-dependent manner. Testing of M. catarrhalis O35E katA and ahpC mutants for their abilities to scavenge exogenous H2O2 showed that the KatA catalase was responsible for most of this activity in the wild-type parent strain. The introduction of the same mutations into M. catarrhalis strain ETSU-4 showed that the growth of a ETSU-4 katA mutant was markedly inhibited by the addition of 50 mM H2O2 but that this mutant could still form a biofilm equivalent to that produced by its wild-type parent strain.

Hoopman, Todd C.; Liu, Wei; Joslin, Stephanie N.; Pybus, Christine; Brautigam, Chad A.; Hansen, Eric J.

2011-01-01

62

Conservation of outer membrane protein E among strains of Moraxella catarrhalis.  

PubMed

Outer membrane protein E (OMP E) is a 50-kDa protein of Moraxella catarrhalis which has several features that suggest that the protein may be an effective vaccine antigen. To assess the conservation of OMP E among strains of M. catarrhalis, 22 isolates were studied with eight monoclonal antibodies which recognize epitopes on different regions of the protein. Eighteen of 22 strains were reactive with all eight antibodies. The sequences of ompE from 16 strains of M. catarrhalis were determined, including the 4 strains which were nonreactive with selected monoclonal antibodies. Analysis of sequences indicate a high degree of conservation among strains, with sequence differences clustered in limited regions of the gene. To assess the stability of ompE during colonization of the human respiratory tract, the sequences of ompE of isolates collected from patients colonized with the same strain for 3 to 9 months were determined. The sequences remained unchanged. These results indicate that OMP E is highly conserved among strains of M. catarrhalis, and preliminary studies indicate that the gene which encodes OMP E remains stable during colonization of the human respiratory tract. PMID:11349016

Murphy, T F; Brauer, A L; Yuskiw, N; McNamara, E R; Kirkham, C

2001-06-01

63

Characterization of a Cluster of Three Glycosyltransferase Enzymes Essential for Moraxella catarrhalis Lipooligosaccharide Assembly  

PubMed Central

Moraxella catarrhalis isolates express lipooligosaccharide (LOS) molecules on their surface, which share epitopes similar to that of the Neisseria and Haemophilus species. These common LOS epitopes have been implicated in various steps of pathogenesis for the different organisms. In this study, a cluster of three LOS glycosyltransferase genes (lgt) were identified in M. catarrhalis 7169, a strain that produces a serotype B LOS. Mutants in these glycosyltransferase genes were constructed, and the resulting LOS phenotypes were consistent with varying degrees of truncation compared to wild-type LOS. The LOS structures of each lgt mutant were no longer detected by a monoclonal antibody (MAb 4G5) specific to a highly conserved terminal epitope nor by a monoclonal antibody (MAb 3F7) specific to the serotype B LOS side chain. Mass spectrometry of the LOS glycoforms assembled by two of these lgt mutants indicated that lgt1 encodes an ?(1-2) glucosyltransferase and the lgt2 encodes a ?(1-4) galactosyltransferase. However, these structural studies could not delineate the function for lgt3. Therefore, M. catarrhalis lgt3 was introduced into a defined ?(1-4) glucosyltransferase Haemophilus ducreyi 35000glu? mutant in trans, and monoclonal antibody analysis confirmed that Lgt3 complemented the LOS defect. These data suggest that lgt3 encodes a glucosyltransferase involved in the addition of a ?(1-4)-linked glucose to the inner core. Furthermore, we conclude that this enzymatic step is essential for the assembly of the complete LOS glycoform expressed by M. catarrhalis 7169.

Edwards, Katie J.; Allen, Simon; Gibson, Bradford W.; Campagnari, Anthony A.

2005-01-01

64

Activities of Ceftobiprole, a Novel Broad-Spectrum Cephalosporin, against Haemophilus influenzae and Moraxella catarrhalis  

Microsoft Academic Search

Ceftobiprole, a broad-spectrum pyrrolidinone-3-ylidenemethyl cephem currently in phase III clinical trials, had MICs between 0.008 g\\/ml and 8.0 g\\/ml for 321 clinical isolates of Haemophilus influenzae and between <0.004 g\\/ml and 1.0 g\\/ml for 49 clinical isolates of Moraxella catarrhalis. Ceftobiprole MIC50 and MIC90 values for H. influenzae were 0.06 g\\/ml and 0.25 g\\/ml for -lactamase-positive strains (n 262), 0.03

Tatiana Bogdanovich; Catherine Clark; Lois Ednie; Gengrong Lin; Kathy Smith; Stuart Shapiro; Peter C. Appelbaum

2006-01-01

65

C4-Alkylthiols with activity against Moraxella catarrhalis and Mycobacterium tuberculosis  

PubMed Central

Antimicrobial resistance represents a global threat to healthcare. The ability to adequately treat infectious diseases is increasingly under siege due to the emergence of drug-resistant microorganisms. New approaches to drug development are especially needed to target organisms that exhibit broad antibiotic resistance due to expression of ?-lactamases which is the most common mechanism by which bacteria become resistant to ?-lactam antibiotics. We designed and synthesized 20 novel monocyclic ?-lactams with alkyl- and aryl-thio moieties at C4, and subsequently tested these for antibacterial activity. These compounds demonstrated intrinsic activity against serine ?-lactamase producing Mycobacterium tuberculosis wild type strain (Mtb) and multiple (n = 6) ?-lactamase producing Moraxella catarrhalis clinical isolates.

Kostova, Maya B.; Myers, Carey J.; Beck, Tim N.; Plotkin, Balbina J.; Green, Jacalyn M.; Boshoff, Helena I.M.; Barry, Clifton E.; Deschamps, Jeffrey R.; Konaklieva, Monika I.

2013-01-01

66

Mutant Lipooligosaccharide-Based Conjugate Vaccine Demonstrates a Broad-Spectrum Effectiveness against Moraxella catarrhalis  

PubMed Central

There is no licensed vaccine available against Moraxella catarrhalis, an exclusive human pathogen responsible for otitis media in children and respiratory infections in adults. We previously developed conjugate vaccine candidates based on lipooligosaccharides (LOSs) of M. catarrhalis serotypes A, B, and C, each of which was shown to cover a portion of the clinical strains. To generate conserved LOS antigens and eliminate a potential autoimmune response to a similar epitope between M. catarrhalis LOS moiety Gal?1-4Gal?1-4Glc and human Pk antigen, two LOS mutants from strain O35E were constructed. Mutant O35Elgt5 or O35EgalE revealed a deletion of one or two terminal galactose residues of wild type O35E LOS. Each LOS molecule was purified, characterized, detoxified, and coupled to tetanus toxoid (TT) to form conjugates, namely dLOS-TT. Three subcutaneous immunizations using dLOS-TT from O35Elgt5 or O35EgalE elicited significant increases (a 729- or 1263-fold above the preimmune serum levels) of serum immunoglobulin (Ig)G against O35E LOS in rabbits with an adjuvant or without an adjuvant (an 140- or 140-fold above the preimmune serum levels). Rabbit antisera demonstrated elevated complement-mediated bactericidal activities against the wild type strain O35E. The rabbit sera elicited by O35Elgt5 dLOS-TT were further examined and showed cross bactericidal activity against all additional 19 M. catarrhalis strains and clinical isolates studied. Moreover, the rabbit sera displayed cross-reactivity not only among three serotype strains but also clinical isolates in a whole-cell enzyme-linked immunosorbent assay (ELISA), which was further confirmed under transmission electron microscopy. In conclusion, O35Elgt5 dLOS-TT may act as a vaccine against most M. catarrhalis strains and therefore can be used for further in vivo efficacy studies.

Ren, Dabin; Yu, Shengqing; Gao, Song; Peng, Daxin; Petralia, Ronald S.; Muszynski, Artur; Carlson, Russell W.; Robbins, John B.; Lim, David J.; Gu, Xin-Xing

2011-01-01

67

Antimicrobial activity and in vitro susceptibility test development for cefditoren against Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus species  

Microsoft Academic Search

Cefditoren, a third generation orally administered aminothiazolyl cephalosporin, has demonstrated bactericidal activity against many Gram positive and negative bacterial pathogens and stability against clinically important ?-lactamases. Cefditoren was compared to cefaclor, cefixime, and penicillins against 1 435 recently isolated strains of streptococci (312 Streptococcus pneumoniae, 165 viridans group streptococci, 142 ?-haemolytic streptococci), Haemophilus influenzae (521 strains), and Moraxella catarrhalis (295

David M. Johnson; Douglas J. Biedenbach; Mondell L. Beach; Michael A. Pfaller; Ronald N. Jones

2000-01-01

68

The major outer membrane protein, CD, extracted from Moraxella (Branhamella) catarrhalis is a potential vaccine antigen that induces bactericidal antibodies  

Microsoft Academic Search

The major outer membrane protein of Moraxella (Branhamella) catarrhalis, CD, was detergent-extracted from the bacterial cell wall and purified to homogeneity in high yields by a simple process. The purified protein appeared to exhibit immunogenic properties similar to those of native CD exposed on the surface of the bacterium. Antibodies to CD raised in mice specifically bound to intact B.

Yan-ping Yang; Lisa E Myers; Ursula McGuinness; Pele Chong; Yan Kwok; Michel H Klein; Robin E Harkness

1997-01-01

69

Antimicrobial susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolated in two successive respiratory seasons in the US  

Microsoft Academic Search

Antimicrobial susceptibilities of clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were determined in two consecutive respiratory seasons in the US and suggested that national susceptibilities to commonly tested antimicrobials changed only slightly from the 1999–2000 to the 2000–2001 respiratory season. However, a significant regional variation in S. pneumoniae susceptibilities was observed, as was a decrease in ?-lactamase

James A Karlowsky; Deborah C Draghi; Clyde Thornsberry; Mark E Jones; Ian A Critchley; Daniel F Sahm

2002-01-01

70

Functional characteristics of a protective monoclonal antibody against serotype A and C lipooligosaccharides from Moraxella catarrhalis.  

PubMed

A monoclonal antibody (MAb), designated MAb 8E7 (immunoglobulin G3), specific for Moraxella catarrhalis lipooligosaccharide (LOS) was evaluated for its functional activity in vitro and in a mouse model of colonization. Enzyme-linked immunosorbent assay (ELISA) demonstrated that the MAb 8E7 could be prepared to a high titer against LOS of the homologous strain 035E, and that it had bactericidal activity. MAb 8E7 reacted with M. catarrhalis serotype A and C LOSs but not serotype B LOS, as measured by ELISA and Western blotting. On the basis of published structures of LOSs, this suggests that the epitope recognized by MAb 8E7 is directed to a common sequence of either alpha-GlcNAc-(1-->2)-beta-Glc-(1--> at the branch substituting position 4 of the trisubstituted Glc residue or a terminal tetrasaccharide alpha-Gal-(1-->4)-beta-Gal-(1-->4)-alpha-Glc-(1-->2)-beta-Glc-(1--> at the branch substituting position 6 of the trisubstituted Glc residue. In a whole-cell ELISA, MAb 8E7 reacted with 70% of the 30 wild-type strains and clinical isolates tested. Immuno-electron microscopy demonstrated that MAb 8E7 reacted with a cell surface-exposed epitope of LOS on strain O35E. MAb 8E7 inhibited the adherence of strain O35E to Chang conjunctival epithelial cells by 90%. Passive immunization with MAb 8E7 could significantly enhance the clearance of strain O35E from mouse lungs in an aerosol challenge mouse model. This enhanced bacterial clearance was inhibited when MAb 8E7 was absorbed by M. catarrhalis serotype A LOS, indicating that the M. catarrhalis LOS-directed antibody may play a major role in the enhancement of M. catarrhalis clearance from lungs. These data suggest that MAb 8E7, which recognizes surface-exposed LOS of M. catarrhalis, is a protective antibody against M. catarrhalis. PMID:11179299

Hu, W G; Chen, J; McMichael, J C; Gu, X X

2001-03-01

71

Bactericidal monoclonal antibody against Moraxella catarrhalis lipooligosaccharide cross-reacts with Haemophilus Spp.  

PubMed

Monoclonal antibodies (MAbs) against lipooligosaccharide (LOS) determinants after immunization of BALB/c mice with heat inactivated Moraxella catarrhalis serotype A were generated. MAb 219A9 was specific for a common epitope of A, B, and C M. catarrhalis serotypes in ELISA and immunofluorescent test (IFT). In both tests it also cross-reacted with whole bacteria and LPS antigens isolated from non-typeable H. influenzae and H. parainfluenzae strains. IgM antibody clone 219A9 possessed a strong bactericidal effect against the three serotypes in the presence of complement. Our results demonstrate that antibodies directed to a single LOS epitope common for A, B, and C serotype could be highly protective. This suggests that the common determinants are very promising in the development of LOS-based vaccine against M. catarrhalis. The cross-reactions of MAb 219A9 with Haemophilus spp. also show that immunization could result in immune response to epitopes conserved in other important respiratory pathogens. PMID:17211546

Gergova, Raina T; Iankov, Ianko D; Haralambieva, Iana H; Mitov, Ivan G

2007-02-01

72

Correlation between susceptibility and BRO type enzyme of Moraxella catarrhalis strains.  

PubMed

Clinical isolates of Moraxella catarrhalis (76 isolates) were screened for beta-lactamase production and antibiotic susceptibility. beta-Lactamases (detected in 90.8% of isolates) were typed using isoelectric focusing to BRO-1 (87%) and BRO-2 (13%). Minor variations in electrofocusing patterns between the two types were seen. Isolates expressing BRO type enzymes showed solid resistance to penicillin, ampicillin and cephalothin, in particular BRO-1 producers. BRO-1 isolates were less susceptible to cephems and to beta-lactamase inhibitors than BRO-2 isolates. Isolates harbouring BRO-1 enzymes have more enzymatic activity than those expressed by BRO-2 isolates. Apart from resistance to tetracycline (14.5%), all isolates were consistently susceptible to erythromycin, chloramphenicol, ciprofloxacin and gentamicin. The conjugal transfer of BRO beta-lactamase gene(s) between M. catarrhalis isolates occurred with a frequency of 10(-5) to 10(-7)/donor cell. The data emphasize the importance of M. catarrhalis as an etiological agent spreading beta-lactamases that may inhibit some beta-lactams and lead to failure in treatment of mixed infections. PMID:14602374

Kadry, Ashraf A; Fouda, Soliman I; Elkhizzi, Noura A; Shibl, Atef M

2003-11-01

73

A prospective study of intrafamilial transmission and antimicrobial susceptibility of Moraxella catarrhalis.  

PubMed

Moraxella catarrhalis has been recognized as a particularly threatening respiratory tract pathogen in humans. A prospective study was performed to investigate which strains of M. catarrhalis can be transmitted within families; the study also addressed features of antimicrobial susceptibility. Seventy-five strains were isolated from six participants between July 2002 and February 2004, including 73 that were verified as beta-lactamase-producing strains. Antimicrobial susceptibility was tested for six types of antibiotics and no treatment issues were found. Pulsed-field gel electrophoresis (PFGE) was performed on all strains and 25 independent PFGE patterns were detected. The dominant pattern L (defined in the present study) was found in 21 (28%) of strains that were continuously recovered from children from the same family over an 8-month period. Strains with the patterns G, J, L, M, R, S, U, and W seemed to spread among the children, but there was no evidence of child-parent transmission. In the present study, the characteristics of M. catarrhalis within families have been documented, and PFGE profiles found to reveal alternating colonization and intrafamilial transmission. PMID:21668485

Masaki, Hironori; Qin, Liang; Zhou, Zhaoyan; Onizuka, Tomoko; Watanabe, Kiwao; Hu, Bijie; Watanabe, Hiroshi

2011-09-01

74

Analysis of Moraxella catarrhalis by DNA typing: evidence for a distinct subpopulation associated with virulence traits.  

PubMed

Two DNA typing methods, probe-generated restriction fragment length polymorphism analysis and single-adapter amplified fragment length polymorphism analysis, were used to study the genetic relationships among 90 Moraxella catarrhalis strains. Both methods were found to be highly concordant, generating a dendrogram with 2 main branches. The division of the M. catarrhalis population into 2 subspecies was supported by analysis of the 16S rRNA sequences. Both beta-lactamase-positive and beta-lactamase-negative strains were found in all main branches, suggesting horizontal transfer of the beta-lactamase gene. In contrast, 2 virulence traits, complement resistance and adherence to epithelial cells, were strongly associated with 1 of the 2 subspecies. The branch depth suggested that complement-resistant adherent strains diverged from a common ancestor more recently than did complement-sensitive nonadherent strains. These findings suggest the existence of subpopulations of M. catarrhalis that differ in virulence, and they may have implications for vaccine development. PMID:10762569

Bootsma, H J; van der Heide, H G; van de Pas, S; Schouls, L M; Mooi, F R

2000-04-01

75

Investigation of mucosal immunisation in pulmonary clearance of Moraxella (Branhamella) catarrhalis.  

PubMed

Moraxella (Branhamella) catarrhalis is a common cause of otitis media in children and respiratory infection in adults with chronic obstructive pulmonary disease. To identify immune responses that may facilitate the development of a mucosal vaccine, a mouse model to study pulmonary responses was established. Regimes involving intra-Peyer's patch, intratracheal and intranasal routes of immunisation with killed M. catarrhalis were investigated. A mucosal immunisation regime of a primary intra-Peyer's patch immunisation with an intratracheal boost resulted in significantly enhanced pulmonary clearance of bacteria compared to controls following an intratracheal challenge with live bacteria. Additional intratracheal boosts did not induce further enhancement of clearance. Intra-Peyer's patch immunisation alone, intratracheal and intranasal immunisations did not induce enhanced clearance. The levels of specific IgG and IgA in serum and bronchoalveolar lavage fluid correlated with pulmonary clearance. The present study showed that mucosal immunisation induced enhanced pulmonary clearance of M. catarrhalis following live bacterial challenge. This mucosal immunisation model has demonstrated that a mucosal vaccine, particularly an oral vaccine, would be feasible. PMID:10519928

Kyd, J; John, A; Cripps, A; Murphy, T F

1999-10-14

76

Possible relationship of PFGE patterns of Moraxella catarrhalis between hospital- and community-acquired respiratory infections in a community hospital.  

PubMed

We describe a prospective study of molecular analysis of Moraxella catarrhalis isolated from a community hospital. Our study was designed to investigate the possible relationship of pulsed-field gel electrophoresis (PFGE) patterns of M. catarrhalis between hospital- and community-acquired respiratory infections. A nosocomial outbreak of M. catarrhalis was observed between September 2000 and September 2001. During the study period, 40 strains of M. catarrhalis were isolated from a total of 32 patients with respiratory infections (26 strains from 18 inpatients, and 14 strains from 14 outpatients). We compared the PFGE patterns in 40 strains of M. catarrhalis isolated from the respiratory tract of the study patients. The genomic types of M. catarrhalis were classified into three PFGE patterns (A, B, and C). Interestingly, the nosocomial outbreak of M. catarrhalis included two patterns (A and B). Of the three patterns, two patterns (A and B) were found in both inpatients and outpatients. More interestingly, two subtypes of pattern B (B1 and B4) were simultaneously found in both inpatients and outpatients. Our results indicated that PFGE with SmaI chromosomal digestion is a suitable technique to establish the inter-strain genetic relatedness of M. catarrhalis, and suggested that the outbreak of M. catarrhalis occasionally included miscellaneous PFGE patterns. The results also showed that PFGE patterns of M. catarrhalis isolates were similar between hospital- and community-acquired respiratory infections. Analysis of the subtypes suggested that there might be some association between hospital- and community-acquired respiratory infections caused by M. catarrhalis. PMID:12906097

Masaki, Hironori; Asoh, Norichika; Kawazoe, Kaneo; Watanabe, Kiwao; Onizuka, Tomoko; Shimogama, Seiji; Yamaryo, Takeshi; Watanabe, Hiroshi; Oishi, Kazunori; Nagatake, Tsuyoshi

2003-01-01

77

Towards understanding the functional role of the glycosyltransferases involved in the biosynthesis of Moraxella catarrhalis lipooligosaccharide.  

PubMed

The glycosyltransferase enzymes (Lgts) responsible for the biosynthesis of the lipooligosaccharide-derived oligosaccharide structures from Moraxella catarrhalis have been investigated. This upper respiratory tract pathogen is responsible for a spectrum of illnesses, including otitis media (middle ear infection) in children, and contributes to exacerbations of chronic obstructive pulmonary disease in elderly patients. To investigate the function of the glycosyltransferase enzymes involved in the biosynthesis of lipooligosaccharide of M. catarrhalis and to gain some insight into the mechanism of serotype specificity for this microorganism, mutant strains of M. catarrhalis were produced. Examination by NMR and MS of the oligosaccharide structures produced by double-mutant strains (2951lgt1/4Delta and 2951lgt5/4Delta) and a single-mutant strain (2951lgt2Delta) of the bacterium has allowed us to propose a model for the serotype-specific expression of lipooligosaccharide in M. catarrhalis. According to this model, the presence/absence of Lgt4 and the Lgt2 allele determines the lipooligosaccharide structure produced by a strain. Furthermore, it is concluded that Lgt4 functions as an N-acetylglucosylamine transferase responsible for the addition of an alpha-D-GlcNAc (1-->2) glycosidic linkage to the (1-->4) branch, and also that there is competition between the glycosyltransferases Lgt1 and Lgt4. That is, in the presence of an active Lgt4, GlcNAc is preferentially added to the (1-->4) chain of the growing oligosaccharide, instead of Glc. In serotype B strains, which lack Lgt4, Lgt1 adds a Glc at this position. This implies that active Lgt4 has a much higher affinity/specificity for the beta-(1-->4)-linked Glc on the (1-->4) branch than does Lgt1. PMID:17388814

Peak, Ian R; Grice, I D; Faglin, Isabelle; Klipic, Zoran; Collins, Patrick M; van Schendel, Lucien; Hitchen, Paul G; Morris, Howard R; Dell, Anne; Wilson, Jennifer C

2007-04-01

78

Innate immune properties of selected human neuropeptides against Moraxella catarrhalis and nontypeable Haemophilus influenzae  

PubMed Central

Background Considerable evidence supports the concept of active communication between the nervous and immune systems. One class of such communicators are the neuropeptides (NPs). Recent reports have highlighted the antimicrobial activity of neuropeptides, placing them among the integral components of innate immune defense. This study examined the action of four human neuropeptides: calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), substance P (SP) and somatostatin (SOM), which are accessible in the upper respiratory tract, against two human-specific respiratory pathogens. We studied: (i) neuropeptide-mediated direct antibacterial activity exerted against Moraxella catarrhalis and nontypeable Haemophilus influenzae, and (ii) indirect immunomodulatory role of these neuropeptides in the neutrophil-mediated phagocytosis of indicated pathogens. Results We found that 100 micromolar concentrations of CGRP, NPY, SP, and SOM effectively permeabilized bacterial membranes and showed (except SOM) bactericidal activity against both pathogens. SOM acted only bacteriostatically. However the killing efficacy was dependent on the bactericidal assay used. The rank order of killing NP effect was: NPY ? CGRP > SP >> SOM and correlated with their potency to permeabilize bacterial membranes. The killing and permeabilization activity of the analyzed NPs showed significant correlation with several physicochemical properties and amino acid composition of the neuropeptides. M. catarrhalis was more sensitive to neuropeptides than nontypeable H. influenzae. The immunomodulatory bimodal effect of physiological concentrations of CGRP, NPY, and SP on the phagocytic function of human neutrophils against M. catarrhalis and H. influenzae was observed both in the ingestion (pathogen uptake) and reactive oxygen species generation stages. This effect was also dependent on the distinct type of pathogen recognition (opsonic versus nonopsonic). Conclusions The present results indicate that neuropeptides such as CGRP, NPY, and SP can effectively participate in the direct and indirect elimination of human-specific respiratory pathogens. Because the studied NPs show both direct and indirect modulating antimicrobial potency, they seem to be important molecules involved in the innate host defense against M. catarrhalis and nontypeable H. influenzae.

2012-01-01

79

Comparative Antimicrobial Activity and Kill-Curve Investigations of Novel Ketolide Antimicrobial Agents (HMR 3004 and HMR 3647) Tested against Haemophilus influenzae and Moraxella catarrhalis Strains  

Microsoft Academic Search

The activity of two ketolide compounds, HMR 3004 and 3647, were compared to those of five macrolides, quinupristin\\/dalfopristin, ciprofloxacin, and ampicillin. The rate of killing for the ketolides was also assessed against Haemophilus influenzae and Moraxella catarrhalis. One hundred H. influenzae and 148 M. catarrhalis isolates were tested using broth microdilution and appropriate growth media. The killing rates of HMR

Douglas J Biedenbach; Mary S Barrett; Ronald N Jones

1998-01-01

80

Use of an Isogenic Mutant Constructed in Moraxella catarrhalis To Identify a Protective Epitope of Outer Membrane Protein B1 Defined by Monoclonal Antibody 11C6  

Microsoft Academic Search

Moraxella catarrhalis-induced otitis media continues to be a significant cause of infection in young children, prompting increased efforts at identifying effective vaccine antigens. We have previously demonstrated that M. catarrhalis expresses specific outer membrane proteins (OMPs) in response to iron limitation and that this organism can utilize transferrin and lactoferrin for in vitro growth. One of these proteins, which binds

Nicole R. Luke; Thomas A. Russo; Neal Luther; Anthony A. Campagnari

81

Evaluation of susceptibility patterns and BRO beta-lactamase types among clinical isolates of Moraxella catarrhalis.  

PubMed

The aims of this study were to detect BRO beta-lactamase types and to evaluate any correlation with the susceptibility patterns of 90 clinical isolates of Moraxella catarrhalis. The overall prevalences of the bro-1 and bro-2 genes were 78% and 12%, respectively. Penicillin G MICs for BRO-1+ isolates were significantly higher than those for BRO-2+ isolates. All the isolates were susceptible to amoxycillin-clavulanate, levofloxacin and cefixime. Resistance to clarithromycin, tetracycline and trimethoprim-sulphamethoxazole was 1.1%, 2.2% and 1.1%, respectively. One-step, length-based PCR was an efficient method to screen for BRO beta-lactamase genes. PMID:17608812

Esel, D; Ay-Altintop, Y; Yagmur, G; Gokahmetoglu, S; Sumerkan, B

2007-10-01

82

Salivary antibodies directed against outer membrane proteins of Moraxella catarrhalis in healthy adults.  

PubMed

Moraxella catarrhalis is a major mucosal pathogen of the human respiratory tract, but the mucosal immune response directed against surface components of this organism has not been characterized in detail. The aim of this study was to investigate the salivary immunoglobulin A (IgA) response toward outer membrane proteins (OMP) of M. catarrhalis in healthy adults, the group of individuals least likely to be colonized and thus most likely to display mucosal immunity. Unstimulated saliva samples collected from 14 healthy adult volunteers were subjected to IgA immunoblot analysis with OMP preparations of M. catarrhalis strain O35E. Immunoblot analysis revealed a consistent pattern of IgA reactivity, with the appearance of five major bands located at >250, 200, 120, 80, and 60 kDa. Eleven (79%) of 14 saliva samples elicited reactivity to all five bands. Immunoblot analysis with a set of isogenic knockout mutants lacking the expression of individual OMP was used to determine the identities of OMP giving rise to IgA bands. Human saliva was shown consistently to exhibit IgA-binding activity for oligomeric UspA2 (>250 kDa), hemagglutinin (200 kDa), monomeric UspA1 (120 kDa), transferrin-binding protein B (TbpB), monomeric UspA2, CopB, and presumably OMP CD. TbpB, oligomeric UspA2, and CopB formed a cluster of bands at about 80 kDa. These data indicate that the human salivary IgA response is directed consistently against a small number of major OMP, some of which are presently considered vaccine candidates. The functional properties of these mucosal antibodies remain to be elucidated. PMID:14638765

Stutzmann Meier, Patricia; Heiniger, Nadja; Troller, Rolf; Aebi, Christoph

2003-12-01

83

Salivary Antibodies Directed against Outer Membrane Proteins of Moraxella catarrhalis in Healthy Adults  

PubMed Central

Moraxella catarrhalis is a major mucosal pathogen of the human respiratory tract, but the mucosal immune response directed against surface components of this organism has not been characterized in detail. The aim of this study was to investigate the salivary immunoglobulin A (IgA) response toward outer membrane proteins (OMP) of M. catarrhalis in healthy adults, the group of individuals least likely to be colonized and thus most likely to display mucosal immunity. Unstimulated saliva samples collected from 14 healthy adult volunteers were subjected to IgA immunoblot analysis with OMP preparations of M. catarrhalis strain O35E. Immunoblot analysis revealed a consistent pattern of IgA reactivity, with the appearance of five major bands located at >250, 200, 120, 80, and 60 kDa. Eleven (79%) of 14 saliva samples elicited reactivity to all five bands. Immunoblot analysis with a set of isogenic knockout mutants lacking the expression of individual OMP was used to determine the identities of OMP giving rise to IgA bands. Human saliva was shown consistently to exhibit IgA-binding activity for oligomeric UspA2 (>250 kDa), hemagglutinin (200 kDa), monomeric UspA1 (120 kDa), transferrin-binding protein B (TbpB), monomeric UspA2, CopB, and presumably OMP CD. TbpB, oligomeric UspA2, and CopB formed a cluster of bands at about 80 kDa. These data indicate that the human salivary IgA response is directed consistently against a small number of major OMP, some of which are presently considered vaccine candidates. The functional properties of these mucosal antibodies remain to be elucidated.

Stutzmann Meier, Patricia; Heiniger, Nadja; Troller, Rolf; Aebi, Christoph

2003-01-01

84

Construction and Characterization of Moraxella catarrhalis Mutants Defective in Expression of Transferrin Receptors  

PubMed Central

We have previously reported the construction of an isogenic mutant defective in expression of OmpB1, the TbpB homologue, in Moraxella catarrhalis 7169. In this report, we have extended these studies by constructing and characterizing two new isogenic mutants in this clinical isolate. One mutant is defective in expression of TbpA, and the other mutant is defective in expression of both TbpA and TbpB. These isogenic mutants were confirmed by using PCR analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and sequencing. In vitro growth studies, comparing all three mutants, demonstrated that the tbpA mutant and the tbpAB mutant were severely limited in their ability to grow with human holotransferrin as the sole source of iron. In contrast, the ompB1 (tbpB) mutant was capable of utilizing iron from human transferrin, although not to the extent of the parental strain. While affinity chromatography with human holotransferrin showed that each Tbp was capable of binding independently to transferrin, solid-phase transferrin binding studies using whole cells demonstrated that the tbpA mutant exhibited binding characteristics similar to those seen with the wild-type bacteria. However, the ompB1 (tbpB) mutant exhibited a diminished capacity for binding transferrin, and no binding was detected with the double mutant. These data suggest that the M. catarrhalis TbpA is necessary for the acquisition of iron from transferrin. In contrast, TbpB is not essential but may serve as a facilitory protein that functions to optimize this process. Together these mutants are essential to provide a more thorough understanding of iron acquisition mechanisms utilized by M. catarrhalis.

Luke, Nicole R.; Campagnari, Anthony A.

1999-01-01

85

RNA-Seq-Based Analysis of the Physiologic Cold Shock-Induced Changes in Moraxella catarrhalis Gene Expression  

PubMed Central

Background Moraxella catarrhalis, a major nasopharyngeal pathogen of the human respiratory tract, is exposed to rapid downshifts of environmental temperature when humans breathe cold air. The prevalence of pharyngeal colonization and respiratory tract infections caused by M. catarrhalis is greatest in winter. We investigated how M. catarrhalis uses the physiologic exposure to cold air to regulate pivotal survival systems that may contribute to M. catarrhalis virulence. Results In this study we used the RNA-seq techniques to quantitatively catalogue the transcriptome of M. catarrhalis exposed to a 26°C cold shock or to continuous growth at 37°C. Validation of RNA-seq data using quantitative RT-PCR analysis demonstrated the RNA-seq results to be highly reliable. We observed that a 26°C cold shock induces the expression of genes that in other bacteria have been related to virulence a strong induction was observed for genes involved in high affinity phosphate transport and iron acquisition, indicating that M. catarrhalis makes a better use of both phosphate and iron resources after exposure to cold shock. We detected the induction of genes involved in nitrogen metabolism, as well as several outer membrane proteins, including ompA, m35-like porin and multidrug efflux pump (acrAB) indicating that M. catarrhalis remodels its membrane components in response to downshift of temperature. Furthermore, we demonstrate that a 26°C cold shock enhances the induction of genes encoding the type IV pili that are essential for natural transformation, and increases the genetic competence of M. catarrhalis, which may facilitate the rapid spread and acquisition of novel virulence-associated genes. Conclusion Cold shock at a physiologically relevant temperature of 26°C induces in M. catarrhalis a complex of adaptive mechanisms that could convey novel pathogenic functions and may contribute to enhanced colonization and virulence.

Spaniol, Violeta; Wyder, Stefan; Aebi, Christoph

2013-01-01

86

The evaluation of putative endogenous control housekeeping genes for real-time polymerase chain reaction expression studies in Moraxella catarrhalis.  

PubMed

Comparisons of endogenous control genes in real-time polymerase chain reaction gene expression studies involving Moraxella catarrhalis are rare. This study shows that a combination of the iron sequestering gene copB and 16S rRNA genes would be useful for lineage 1 (16S rRNA type 1) isolates, but not lineage 2 (16S rRNA types 2 and 3) isolates. PMID:19717264

Hays, John P

2009-11-01

87

Activities of Faropenem, an Oral  Lactam, against Recent U.S. Isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis  

Microsoft Academic Search

The in vitro activities of faropenem and other antimicrobial agents were determined against 4,725 Strepto- coccus pneumoniae isolates, 2,614 Haemophilus influenzae isolates, and 1,193 Moraxella catarrhalis isolates collected from 273 U.S. laboratories during 1999. Faropenem MICs at which 90% of isolates are inhibited were 0.008, 0.25, and 1 g\\/ml for penicillin-susceptible, -intermediate, and -resistant S. pneumoniae strains, respec- tively; 0.5

Ian A. Critchley; James A. Karlowsky; Deborah C. Draghi; Mark E. Jones; Clyde Thornsberry; Kate Murfitt; Daniel F. Sahm

2002-01-01

88

Residence of Streptococcus pneumoniae and Moraxella catarrhalis within polymicrobial biofilm promotes antibiotic resistance and bacterial persistence in vivo.  

PubMed

Otitis media (OM) is an extremely common pediatric ailment caused by opportunists that reside within the nasopharynx. Inflammation within the upper airway can promote ascension of these opportunists into the middle ear chamber. OM can be chronic/recurrent in nature, and a wealth of data indicates that in these cases, the bacteria persist within biofilms. Epidemiological data demonstrate that most cases of OM are polymicrobial, which may have significant impact on antibiotic resistance. In this study, we used in vitro biofilm assays and rodent infection models to examine the impact of polymicrobial infection with Moraxella catarrhalis and Streptococcus pneumoniae (pneumococcus) on biofilm resistance to antibiotic treatment and persistence in vivo. Consistent with prior work, M. catarrhalis conferred beta-lactamase-dependent passive protection from beta-lactam killing to pneumococci within polymicrobial biofilms. Moreover, pneumococci increased resistance of M. catarrhalis to macrolide killing in polymicrobial biofilms. However, pneumococci increased colonization in vivo by M. catarrhalis in a quorum signal-dependent manner. We also found that co-infection with M. catarrhalis affects middle ear ascension of pneumococci in both mice and chinchillas. Therefore, we conclude that residence of M. catarrhalis and pneumococci within the same biofilm community significantly impacts resistance to antibiotic treatment and bacterial persistence in vivo. PMID:24391058

Perez, Antonia C; Pang, Bing; King, Lauren B; Tan, Li; Murrah, Kyle A; Reimche, Jennifer L; Wren, John T; Richardson, Stephen H; Ghandi, Uma; Swords, W Edward

2014-04-01

89

Enhancement of pulmonary clearance of Moraxella (Branhamella) catarrhalis following immunization with outer membrane protein CD in a mouse model.  

PubMed

Moraxella (Branhamella) catarrhalis is an important human respiratory tract pathogen. Outer membrane protein (OMP) CD is highly conserved among strains and has characteristics that indicate it may be an effective vaccine antigen. This study investigated the effect of immunization with OMP CD on pulmonary clearance following intratracheal challenge of mice with M. catarrhalis. Two routes of immunization were studied: mucosal immunization (intra-Peyer's patch followed by intratracheal boost) and intramuscular immunization with OMP CD. Both resulted in enhanced pulmonary clearance of M. catarrhalis compared with sham-immunized controls. Immunization with OMP CD induced specific antibodies in serum and bronchoalveolar lavage fluid and induced a specific lymphocyte proliferative response in T cells from mesenteric lymph nodes from mice mucosally immunized with OMP CD. On the basis of these results, OMP CD should undergo continued testing to determine whether it will induce a protective immune response in humans. PMID:9815219

Murphy, T F; Kyd, J M; John, A; Kirkham, C; Cripps, A W

1998-12-01

90

Biological and immunological characteristics of lipooligosaccharide-based conjugate vaccines for serotype C Moraxella catarrhalis.  

PubMed

Moraxella catarrhalis is an important bacterial cause of otitis media in children and respiratory tract infections in the elderly. Lipooligosaccharide (LOS), a major surface antigen of this bacterium, is a potential vaccine component against the organism. There are three major LOS serotypes (serotypes A, B, and C) in clinical isolates of M. catarrhalis. Our previous studies demonstrated that serotype A and B LOS-based conjugates were immunogenic in animals and elicited bactericidal antibodies. In this study, LOS from serotype C strain 26404 was isolated, detoxified, and conjugated to tetanus toxoid (TT) or the cross-reactive mutant (CRM) of diphtheria toxin to form detoxified LOS (dLOS)-TT, dLOS-CRM-1, and dLOS-CRM-2 vaccine candidates. The molar ratios (dLOS/protein) of the resulting conjugates were 47:1, 19:1, and 32:1, respectively, while the weight ratios were 0.94, 0.84 and 1.44, respectively. All conjugates were highly immunogenic in both mouse and rabbit models. Three subcutaneous injections of each conjugate formulated with the Ribi adjuvant elicited >700-fold increases in serum anti-LOS immunoglobulin G levels in mice (5 microg of dLOS) and >2,000-fold increases in rabbits (50 microg of dLOS). The resulting mouse and rabbit antisera showed complement-mediated bactericidal activity against the homologous strain. In addition, a representative rabbit antiserum showed bactericidal activity against 14 of 18 testable strains, and this bactericidal activity could be 100% inhibited by the serotype C or A LOS but only 30% inhibited by the serotype B LOS. These results indicate that the serotype C LOS-based conjugates can be used as vaccine components for further investigation in humans. PMID:17371852

Yu, Shengqing; Gu, Xin-Xing

2007-06-01

91

Identification of a repressor of a truncated denitrification pathway in Moraxella catarrhalis.  

PubMed

Growth of Moraxella catarrhalis in a biofilm resulted in marked upregulation of two open reading frames (ORFs), aniA and norB, predicted to encode a nitrite reductase and a nitric oxide reductase, respectively (W. Wang, L. Reitzer, D. A. Rasko, M. M. Pearson, R. J. Blick, C. Laurence, and E. J. Hansen, Infect. Immun. 75:4959-4971, 2007). An ORF designated nsrR, which was located between aniA and norB, was shown to encode a predicted transcriptional regulator. Inactivation of nsrR resulted in increased expression of aniA and norB in three different M. catarrhalis strains, as measured by both DNA microarray analysis and quantitative reverse transcriptase PCR. Provision of a wild-type nsrR gene in trans in an nsrR mutant resulted in decreased expression of the AniA protein. DNA microarray analysis revealed that two other ORFs (MC ORF 683 and MC ORF 1550) were also consistently upregulated in an nsrR mutant. Consumption of both nitrite and nitric oxide occurred more rapidly with cells of an nsrR mutant than with wild-type cells. However, growth of nsrR mutants was completely inhibited by a low level of sodium nitrite. This inhibition of growth by nitrite was significantly reversed by introduction of an aniA mutation into the nsrR mutant and was completely reversed by the presence of a wild-type nsrR gene in trans. NsrR regulation of the expression of aniA was sensitive to nitrite, whereas NsrR regulation of norB was sensitive to nitric oxide. PMID:18820017

Wang, Wei; Richardson, Anthony R; Martens-Habbena, Willm; Stahl, David A; Fang, Ferric C; Hansen, Eric J

2008-12-01

92

Metabolic analysis of Moraxella catarrhalis and the effect of selected in vitro growth conditions on global gene expression.  

PubMed

The nucleotide sequence from the genome of Moraxella catarrhalis ATCC 43617 was annotated and used both to assess the metabolic capabilities and limitations of this bacterium and to design probes for a DNA microarray. An absence of gene products for utilization of exogenous carbohydrates was noteworthy and could be correlated with published phenotypic data. Gene products necessary for aerobic energy generation were present, as were a few gene products generally ascribed to anaerobic systems. Enzymes for synthesis of all amino acids except proline and arginine were present. M. catarrhalis DNA microarrays containing 70-mer oligonucleotide probes were designed from the genome-derived nucleotide sequence data. Analysis of total RNA extracted from M. catarrhalis ATCC 43617 cells grown under iron-replete and iron-restricted conditions was used to establish the utility of these DNA microarrays. These DNA microarrays were then used to analyze total RNA from M. catarrhalis cells grown in a continuous-flow biofilm system and in the planktonic state. The genes whose expression was most dramatically increased by growth in the biofilm state included those encoding a nitrate reductase, a nitrite reductase, and a nitric oxide reductase. Real-time reverse transcriptase PCR analysis was used to validate these DNA microarray results. These results indicate that growth of M. catarrhalis in a biofilm results in increased expression of gene products which can function not only in energy generation but also in resisting certain elements of the innate immune response. PMID:17620351

Wang, Wei; Reitzer, Larry; Rasko, David A; Pearson, Melanie M; Blick, Robert J; Laurence, Cassie; Hansen, Eric J

2007-10-01

93

Metabolic Analysis of Moraxella catarrhalis and the Effect of Selected In Vitro Growth Conditions on Global Gene Expression? †  

PubMed Central

The nucleotide sequence from the genome of Moraxella catarrhalis ATCC 43617 was annotated and used both to assess the metabolic capabilities and limitations of this bacterium and to design probes for a DNA microarray. An absence of gene products for utilization of exogenous carbohydrates was noteworthy and could be correlated with published phenotypic data. Gene products necessary for aerobic energy generation were present, as were a few gene products generally ascribed to anaerobic systems. Enzymes for synthesis of all amino acids except proline and arginine were present. M. catarrhalis DNA microarrays containing 70-mer oligonucleotide probes were designed from the genome-derived nucleotide sequence data. Analysis of total RNA extracted from M. catarrhalis ATCC 43617 cells grown under iron-replete and iron-restricted conditions was used to establish the utility of these DNA microarrays. These DNA microarrays were then used to analyze total RNA from M. catarrhalis cells grown in a continuous-flow biofilm system and in the planktonic state. The genes whose expression was most dramatically increased by growth in the biofilm state included those encoding a nitrate reductase, a nitrite reductase, and a nitric oxide reductase. Real-time reverse transcriptase PCR analysis was used to validate these DNA microarray results. These results indicate that growth of M. catarrhalis in a biofilm results in increased expression of gene products which can function not only in energy generation but also in resisting certain elements of the innate immune response.

Wang, Wei; Reitzer, Larry; Rasko, David A.; Pearson, Melanie M.; Blick, Robert J.; Laurence, Cassie; Hansen, Eric J.

2007-01-01

94

Outer membrane protein UspA1 and lipooligosaccharide are involved in invasion of human epithelial cells by Moraxella catarrhalis.  

PubMed

Invasion of non-professional phagocytes is a strategy employed by several mucosal pathogens, but has not been investigated in detail for Moraxella catarrhalis, a major cause of human respiratory tract infections. We investigated the role of outer membrane protein (OMP) UspA1 and lipooligosaccharide (LOS) in M. catarrhalis invasion into epithelial cells. An isogenic mutant of strain O35E, which lacked expression of the UspA1 adhesin, demonstrated not only severely impaired adherence (86%) to but also reduced invasion (77%) into Chang conjunctival cells in comparison with the wild-type strain. The isogenic, LOS-deficient mutant strain O35E.lpxA was attenuated in adherence (93%) and its capacity to invade was severely reduced (95%), but not abolished. Inhibition assays using sucrose and cytochalasin D, respectively, demonstrated that clathrin and actin polymerization contribute to internalization of M. catarrhalis by Chang cells. Furthermore, inhibition of UspA1-mediated binding to cell-associated fibronectin and alpha5beta1 integrin decreased invasion of M. catarrhalis strain O35E (72% and 41%, respectively). These data indicate that OMP UspA1 and LOS profoundly affect the capacity of M. catarrhalis to invade epithelial cells. PMID:18069032

Spaniol, Violeta; Heiniger, Nadja; Troller, Rolf; Aebi, Christoph

2008-01-01

95

Substrate Binding Protein SBP2 of a Putative ABC Transporter as a Novel Vaccine Antigen of Moraxella catarrhalis.  

PubMed

Moraxella catarrhalis is a common respiratory tract pathogen that causes otitis media in children and infections in adults with chronic obstructive pulmonary disease. Since the introduction of the pneumococcal conjugate vaccines with/without protein D of nontypeable Haemophilus influenzae, M. catarrhalis has become a high-priority pathogen in otitis media. For the development of antibacterial vaccines and therapies, substrate binding proteins of ATP-binding cassette transporters are important targets. In this study, we identified and characterized a substrate binding protein, SBP2, of M. catarrhalis. Among 30 clinical isolates tested, the sbp2 gene sequence was highly conserved. In 2 different analyses (whole-cell enzyme-linked immunosorbent assay and flow cytometry), polyclonal antibodies raised to recombinant SBP2 demonstrated that SBP2 expresses epitopes on the bacterial surface of the wild type but not the sbp2 mutant. Mice immunized with recombinant SBP2 showed significantly enhanced clearance of M. catarrhalis from the lung compared to that in the control group at both 25-?g and 50-?g doses (P < 0.001). We conclude that SBP2 is a novel, attractive candidate as a vaccine antigen against M. catarrhalis. PMID:24914218

Otsuka, Taketo; Kirkham, Charmaine; Johnson, Antoinette; Jones, Megan M; Murphy, Timothy F

2014-08-01

96

Cold Shock Response of the UspA1 Outer Membrane Adhesin of Moraxella catarrhalis  

PubMed Central

Colonization of the human nasopharynx exposes Moraxella catarrhalis, a common cause of otitis media in children and exacerbations of chronic obstructive pulmonary disease in adults, to sudden downshifts in temperature, occurring when the host breathes cold air. We investigated whether in vitro cold shock influences the expressions of the outer membrane adhesins UspA1 and hemagglutinin, which are considered virulence factors, and of an M. catarrhalis homolog of recA, a housekeeping gene, which in Escherichia coli is induced by cold shock. Quantitative real-time reverse transcriptase PCR was used for measuring mRNA copy number. A screening experiment revealed that a cold shock at 26°C maximally induced the copy number of uspA1. In comparison with 37°C conditions, a 1-hour cold shock at 26°C increased copy numbers of uspA1 and recA by 2.5-fold (11.2 ± 1.8 versus 4.5 ± 0.8 copies/CFU) and 2.7-fold (0.30 ± 0.10 versus 0.11 ± 0.06), respectively, but did not induce transcription of hag. Exposure to 26°C increased surface expression of UspA1, as assessed by fluorescence-activated cell sorter analysis, and resulted in a significant increase in adherence of strain O35E to Chang human conjunctival cells (97.1% ± 2.0% versus 48.3% ± 9.2% at 37°C; P = 0.01). Cold shock induction of uspA1 and recA was detected in strains belonging to either phylogenetic subpopulation of M. catarrhalis (16S rRNA types 1 and 2/3) and was most pronounced in type 2/3 strains (4- to 25-fold for uspA1), which do not express detectable amounts of UspA1 protein at 37°C. These data indicate that cold shock at a physiologically relevant temperature of 26°C induces the expression of at least one virulence factor (UspA1). To our knowledge, no similar data are available for other nasopharyngeal pathogens.

Heiniger, Nadja; Troller, Rolf; Meier, Patricia Stutzmann; Aebi, Christoph

2005-01-01

97

Cold shock response of the UspA1 outer membrane adhesin of Moraxella catarrhalis.  

PubMed

Colonization of the human nasopharynx exposes Moraxella catarrhalis, a common cause of otitis media in children and exacerbations of chronic obstructive pulmonary disease in adults, to sudden downshifts in temperature, occurring when the host breathes cold air. We investigated whether in vitro cold shock influences the expressions of the outer membrane adhesins UspA1 and hemagglutinin, which are considered virulence factors, and of an M. catarrhalis homolog of recA, a housekeeping gene, which in Escherichia coli is induced by cold shock. Quantitative real-time reverse transcriptase PCR was used for measuring mRNA copy number. A screening experiment revealed that a cold shock at 26 degrees C maximally induced the copy number of uspA1. In comparison with 37 degrees C conditions, a 1-hour cold shock at 26 degrees C increased copy numbers of uspA1 and recA by 2.5-fold (11.2 +/- 1.8 versus 4.5 +/- 0.8 copies/CFU) and 2.7-fold (0.30 +/- 0.10 versus 0.11 +/- 0.06), respectively, but did not induce transcription of hag. Exposure to 26 degrees C increased surface expression of UspA1, as assessed by fluorescence-activated cell sorter analysis, and resulted in a significant increase in adherence of strain O35E to Chang human conjunctival cells (97.1% +/- 2.0% versus 48.3% +/- 9.2% at 37 degrees C; P = 0.01). Cold shock induction of uspA1 and recA was detected in strains belonging to either phylogenetic subpopulation of M. catarrhalis (16S rRNA types 1 and 2/3) and was most pronounced in type 2/3 strains (4- to 25-fold for uspA1), which do not express detectable amounts of UspA1 protein at 37 degrees C. These data indicate that cold shock at a physiologically relevant temperature of 26 degrees C induces the expression of at least one virulence factor (UspA1). To our knowledge, no similar data are available for other nasopharyngeal pathogens. PMID:16299321

Heiniger, Nadja; Troller, Rolf; Meier, Patricia Stutzmann; Aebi, Christoph

2005-12-01

98

Interaction of Streptococcus pneumoniae and Moraxella catarrhalis: investigation of the indirect pathogenic role of beta-lactamase-producing moraxellae by use of a continuous-culture biofilm system.  

PubMed

The majority of clinical isolates of Moraxella catarrhalis produce beta-lactamase. The role of this enzyme in the phenomenon of indirect pathogenicity, in which a true pathogen such as Streptococcus pneumoniae is protected from the action of certain beta-lactam antibiotics, is well recognized. By using a simple continuous-culture biofilm system, it has been shown that the pneumococcus attains high titers in excess of 10(12) CFU/biofilm; furthermore, the penicillin-sensitive pneumococcus used remained susceptible to a range of beta-lactam antibiotics in these biofilms (R. K. Budhani and J. K. Struthers, J. Antimicrob. Chemother. 40:601-602, 1997). This system was used to characterize the antibiotic susceptibility of this isolate when grown with beta-lactamase-negative or -positive moraxellae. When grown with beta-lactamase-producing moraxellae in the presence of either benzylpenicillin or amoxicillin, the pneumococcus was protected in the range of the antibiotic concentrations to which it would be considered resistant. With amoxicillin-clavulanic acid the titers of the two organisms collapsed at the antibiotic concentration at which moraxellae became susceptible. The levels of beta-lactamase activity in cell-free supernatants of broth culture, in biofilm, and in biofilm effluent revealed distinct differences in this activity; levels in biofilm were significantly lower than those in broth culture supernatants. The system appears suitable for studying organisms under antibiotic stress and for investigating the interactions of bacteria under such conditions. PMID:9756750

Budhani, R K; Struthers, J K

1998-10-01

99

The UspA1 Protein and a Second Type of UspA2 Protein Mediate Adherence of Moraxella catarrhalis to Human Epithelial Cells In Vitro  

Microsoft Academic Search

The UspA1 and UspA2 proteins of Moraxella catarrhalis are structurally related, are exposed on the bacterial cell surface, and migrate as very high-molecular-weight complexes in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Previous analysis of uspA1 and uspA2 mutants of M. catarrhalis strain 035E indicated that UspA1 was involved in adherence of this organism to Chang conjunctival epithelial cells in vitro and

ERIC R. LAFONTAINE; LESLIE D. COPE; CHRISTOPH AEBI; JO L. LATIMER; G. H. McCracken; E. J. Hansen

2000-01-01

100

Antimicrobial Resistance in Haemophilus influenzae and Moraxella catarrhalis Respiratory Tract Isolates: Results of the Canadian Respiratory Organism Susceptibility Study, 1997 to 2002  

Microsoft Academic Search

A total of 7,566 unique patient isolates of Haemophilus influenzae and 2,314 unique patient isolates of Moraxella catarrhalis were collected between October 1997 and June 2002 from 25 medical centers in 9 of the 10 Canadian provinces. Among the 7,566 H. influenzae isolates, 22.5% produced -lactamase, while 92.4% of the 2,314 M. catarrhalis isolates produced -lactamase. The incidence of -lactamase-producing

George G. Zhanel; Lorraine Palatnick; Kimberly A. Nichol; Don E. Low; D. J. Hoban

2003-01-01

101

Genetic Diversity among Strains of Moraxella catarrhalis: Analysis Using Multiple DNA Probes and a Single-Locus PCR-Restriction Fragment Length Polymorphism Method  

Microsoft Academic Search

Moraxella (Branhamella) catarrhalis, a causative agent of otitis media, sinusitis, and exacerbation of bronchi- tis, has acquired widespread ability to produce b-lactamase and can be nosocomially transmitted. The typing methods used in epidemiological analyses of M. catarrhalis are not optimal for genetic analyses. Two methods, a multiple-locus Southern blot (SB) method and a single-locus PCR-restriction fragment length polymorphism (RFLP) method,

ELAINE S. WALKER; ROBERT A. PRESTON; J. CHRISTOPHER POST; GARTH D. EHRLICH; JOHN H. KALBFLEISCH; KARIN L. KLINGMAN

1977-01-01

102

The Transferrin Binding Protein B of Moraxella catarrhalis Elicits Bactericidal Antibodies and Is a Potential Vaccine Antigen  

PubMed Central

The transferrin binding protein genes (tbpA and tbpB) from two strains of Moraxella catarrhalis have been cloned and sequenced. The genomic organization of the M. catarrhalis transferrin binding protein genes is unique among known bacteria in that tbpA precedes tbpB and there is a third gene located between them. The deduced sequences of the M. catarrhalis TbpA proteins from two strains were 98% identical, while those of the TbpB proteins from the same strains were 63% identical and 70% similar. The third gene, tentatively called orf3, encodes a protein of approximately 58 kDa that is 98% identical between the two strains. The tbpB genes from four additional strains of M. catarrhalis were cloned and sequenced, and two potential families of TbpB proteins were identified based on sequence similarities. Recombinant TbpA (rTbpA), rTbpB, and rORF3 proteins were expressed in Escherichia coli and purified. rTbpB was shown to retain its ability to bind human transferrin after transfer to a membrane, but neither rTbpA nor rORF3 did. Monospecific anti-rTbpA and anti-rTbpB antibodies were generated and used for immunoblot analysis, which demonstrated that epitopes of M. catarrhalis TbpA and TbpB were antigenically conserved and that there was constitutive expression of the tbp genes. In the absence of an appropriate animal model, anti-rTbpA and anti-rTbpB antibodies were tested for their bactericidal activities. The anti-rTbpA antiserum was not bactericidal, but anti-rTbpB antisera were found to kill heterologous strains within the same family. Thus, if bactericidal ability is clinically relevant, a vaccine comprising multiple rTbpB antigens may protect against M. catarrhalis disease.

Myers, Lisa E.; Yang, Yan-ping; Du, Run-pan; Wang, Qijun; Harkness, Robin E.; Schryvers, Anthony B.; Klein, Michel H.; Loosmore, Sheena M.

1998-01-01

103

The Moraxella catarrhalis Immunoglobulin D-Binding Protein MID Has Conserved Sequences and Is Regulated by a Mechanism Corresponding to Phase Variation  

Microsoft Academic Search

The prevalence of the Moraxella catarrhalis immunoglobulin D (IgD)-binding outer membrane protein MID and its gene was determined in 91 clinical isolates and in 7 culture collection strains. Eighty-four percent of the clinical Moraxella strains expressed MID-dependent IgD binding. The mid gene was detected in all strains as revealed by homology of the signal peptide sequence and a conserved area

Andrea Mollenkvist; Therese Nordstrom; Christer Hallden; Jens Jørgen Christensen; Arne Forsgren; Kristian Riesbeck

2003-01-01

104

Genetic diversity among strains of Moraxella catarrhalis cultured from the nasopharynx of young and healthy Brazilian, Angolan and Dutch children.  

PubMed

The present study describes the carriage patterns and genetic variability of Moraxella catarrhalis strains isolated from children living in different countries. Moraxella catarrhalis is genetically heterogeneous, but little is known about its geographic distribution and phenotypic and genetic diversity in warm-climate countries. A collection of 99 isolates from 30 Brazilian, 19 Angolan and 50 Dutch healthy children, all less than 5 years of age, was investigated for phenotypic and genotypic relatedness. The isolates from the three countries were similar where biochemical reactivity was concerned: 89 strains were beta-lactamase-producing and 87 were complement-resistant as determined by phenotype. There was no geographical difference in the prevalence of beta-lactamase-producing isolates, but the carriage rate of complement-resistant strains was significantly higher in Dutch than in Angolan children (P=0.004). Complement resistance of 66 randomly selected strains was genetically confirmed in a Southern hybridization assay by a novel DNA probe that is specific for complement-resistant strains and that demonstrated a sensitivity of 97% and a specificity of 100%. PCR amplification based on the probe sequence had a sensitivity of 98% and a specificity of 57% when compared to the outcome of a conventional culture spot test. PCR restriction fragment length polymorphism analysis of the MU 46 locus and pulsed-field gel electrophoresis of SpeI DNA macrorestriction fragments revealed genetic heterogeneity of strains from within and between the three countries, and no geographical clustering could be established. In conclusion, similar phenotypic characteristics but genotypic heterogeneity was found among Moraxella catarrhalis strains colonizing children in three different continents. PMID:11117640

Wolf, B; Kools-Sijmons, M; Verduin, C; Rey, L C; Gama, A; Roord, J; Verhoef, J; van Belkum, A

2000-10-01

105

Differential Virulence Gene Expression of Group A Streptococcus Serotype M3 in Response to Co-Culture with Moraxella catarrhalis  

PubMed Central

Streptococcus pyogenes (group A Streptococcus, GAS) and Moraxella catarrhalis are important colonizers and (opportunistic) pathogens of the human respiratory tract. However, current knowledge regarding colonization and pathogenic potential of these two pathogens is based on work involving single bacterial species, even though the interplay between respiratory bacterial species is increasingly important in niche occupation and the development of disease. Therefore, to further define and understand polymicrobial species interactions, we investigated whether gene expression (and hence virulence potential) of GAS would be affected upon co-culture with M. catarrhalis. For co-culture experiments, GAS and M. catarrhalis were cultured in Todd-Hewitt broth supplemented with 0.2% yeast extract (THY) at 37°C with 5% CO2 aeration. Each strain was grown in triplicate so that triplicate experiments could be performed. Bacterial RNA was isolated, cDNA synthesized, and microarray transcriptome expression analysis performed. We observed significantly increased (?4-fold) expression for genes playing a role in GAS virulence such as hyaluronan synthase (hasA), streptococcal mitogenic exotoxin Z (smeZ) and IgG endopeptidase (ideS). In contrast, significantly decreased (?4-fold) expression was observed in genes involved in energy metabolism and in 12 conserved GAS two-component regulatory systems. This study provides the first evidence that M. catarrhalis increases GAS virulence gene expression during co-culture, and again shows the importance of polymicrobial infections in directing bacterial virulence.

Verhaegh, Suzanne J. C.; Flores, Anthony R.; van Belkum, Alex; Musser, James M.; Hays, John P.

2013-01-01

106

Identification of an Outer Membrane Lipoprotein Involved in Nasopharyngeal Colonization by Moraxella catarrhalis in an Animal Model.  

PubMed

Colonization of the human nasopharynx by Moraxella catarrhalis is presumed to involve attachment of this bacterium to the mucosa. DNA microarray analysis was used to determine whether attachment of M. catarrhalis to human bronchial epithelial (HBE) cells in vitro affected gene expression in this bacterium. Attachment affected expression of at least 454 different genes, with 163 being upregulated and 291 being downregulated. Among the upregulated genes was one (ORF113) previously annotated as encoding a protein with some similarity to outer membrane protein A (OmpA). The protein encoded by ORF113 was predicted to have a signal peptidase II cleavage site, and globomycin inhibition experiments confirmed that this protein was indeed a lipoprotein. The ORF113 protein also contained a predicted peptidoglycan-binding domain in its C-terminal half. The use of mutant and recombinant M. catarrhalis strains confirmed that the ORF113 protein was present in outer membrane preparations, and this protein was also shown to be at least partially exposed on the bacterial cell surface. A mutant unable to produce the ORF113 protein showed little or no change in its growth rate in vitro, in its ability to attach to HBE cells in vitro, or in its autoagglutination characteristics, but it did exhibit a reduced ability to survive in the chinchilla nasopharynx. This is the first report of a lipoprotein essential to the ability of M. catarrhalis to persist in an animal model. PMID:24643539

Wang, Wei; Joslin, Stephanie N; Pybus, Christine; Evans, Amanda S; Lichaa, Flora; Brautigam, Chad A; Hansen, Eric J

2014-06-01

107

Activities and Postantibiotic Effects of Gemifloxacin Compared to Those of 11 Other Agents against Haemophilus influenzae and Moraxella catarrhalis  

Microsoft Academic Search

The activity of gemifloxacin against Haemophilus influenzae and Moraxella catarrhalis was compared to those of 11 other agents. All quinolones were very active (MICs, <0.125 mg\\/ml) against 248 quinolone-susceptible H. influenzae isolates (40.7% of which were b-lactamase positive); cefixime (MICs, <0.125 mg\\/ml) and amoxicillin- clavulanate (MICs <4.0 mg\\/ml) were active, followed by cefuroxime (MICs, <16.0 mg\\/ml); azithromycin MICs were <4.0

TODD A. DAVIES; LINDA M. KELLY; DIANNE B. HOELLMAN; LOIS M. EDNIE; CATHERINE L. CLARK; SARALEE BAJAKSOUZIAN; MICHAEL R. JACOBS; PETER C. APPELBAUM

2000-01-01

108

Outer membrane porin M35 of Moraxella catarrhalis mediates susceptibility to aminopenicillins  

PubMed Central

Background The outer membrane protein M35 is a conserved porin of type 1 strains of the respiratory pathogen Moraxella catarrhalis. It was previously shown that M35 is involved in the uptake of essential nutrients required for bacterial growth and for nasal colonization in mice. The aim of this study was (i) to characterize the potential roles of M35 in the host-pathogen interactions considering the known multifunctionality of porins and (ii) to characterize the degree of conservation in the phylogenetic older subpopulation (type 2) of M. catarrhalis. Results Isogenic m35 mutants of the type 1 strains O35E, 300 and 415 were tested for their antimicrobial susceptibility against 15 different agents. Differences in the MIC (Minimum Inhibitory Concentration) between wild-type and mutant strains were found for eight antibiotics. For ampicillin and amoxicillin, we observed a statistically significant 2.5 to 2.9-fold MIC increase (p < 0.03) in the m35 mutants. Immunoblot analysis demonstrated that human saliva contains anti-M35 IgA. Wild-type strains and their respective m35 mutants were indistinguishable with respect to the phenotypes of autoagglutination, serum resistance, iron acquisition from human lactoferrin, adherence to and invasion of respiratory tract epithelial cells, and proinflammatory stimulation of human monocytes. DNA sequencing of m35 from the phylogenetic subpopulation type 2 strain 287 revealed 94.2% and 92.8% identity on the DNA and amino acid levels, respectively, in comparison with type 1 strains. Conclusion The increase in MIC for ampicillin and amoxicillin, respectively, in the M35-deficient mutants indicates that this porin affects the outer membrane permeability for aminopenicillins in a clinically relevant manner. The presence of IgA antibodies in healthy human donors indicates that M35 is expressed in vivo and recognized as a mucosal antigen by the human host. However, immunoblot analysis of human saliva suggests the possibility of antigenic variation of immunoreactive epitopes, which warrants further analysis before M35 can be considered a potential vaccine candidate.

2009-01-01

109

Synthesis and characterization of lipooligosaccharide-based conjugate vaccines for serotype B Moraxella catarrhalis.  

PubMed

Moraxella catarrhalis is an important cause of otitis media in children and respiratory tract infections in the elderly. Lipooligosaccharide (LOS) is a major surface antigen of the bacterium that elicits bactericidal antibodies. Serological studies show that three major LOS types (A, B, and C) have been identified among clinical isolates. Our previous studies demonstrated that the type A LOS-based conjugates were immunogenic in animals. In this study, LOS from type B strain 26397 was detoxified and conjugated to tetanus toxoid (TT) or a cross-reactive mutant (CRM) of diphtheria toxin to form detoxified LOS (dLOS)-TT and dLOS-CRM, respectively, as vaccine candidates. The molar ratios of dLOS to TT and CRM in the conjugates were 43:1 and 19:1, respectively, while both weight ratios were around 0.9. The antigenicity of the conjugates was similar to that of the LOS, as determined by enzyme-linked immunosorbent assay using a rabbit antiserum to strain 26397. Subcutaneous immunization with each conjugate elicited a 180- to 230-fold rise of serum anti-LOS immunoglobulin G in mice and >2,000-fold rise in rabbits. In addition, both mouse and rabbit antisera showed elevated complement-mediated bactericidal activity against the homologous strain, and a representative rabbit antiserum showed bactericidal activity against nine of twelve clinical isolates studied. The bactericidal activity of the rabbit antiserum can be fully inhibited by the type B LOS but not the A or C LOS. These results indicate that the type B LOS-based conjugates can be used as vaccine components for further investigation. PMID:15845482

Yu, Shengqing; Gu, Xin-Xing

2005-05-01

110

Binding of vitronectin by the Moraxella catarrhalis UspA2 protein interferes with late stages of the complement cascade.  

PubMed

Many Moraxella catarrhalis strains are resistant to the bactericidal activity of normal human serum (NHS). The UspA2 protein of the serum-resistant strain O35E has previously been shown to be directly involved in conferring serum resistance on this strain. Testing of 11 additional serum-resistant M. catarrhalis wild-type isolates and their uspA1 and uspA2 mutants showed that the uspA1 mutants of all 11 strains were consistently serum resistant and that the uspA2 mutants of these same 11 strains were always serum sensitive. Analysis of complement deposition on four different serum-resistant M. catarrhalis strains and their serum-sensitive uspA2 mutants showed that, for three of these four strain sets, the wild-type and mutant strains bound similar amounts of early complement components. In contrast, there was a significant reduction in the amount of the polymerized C9 on the wild-type strains relative to that on the uspA2 mutants. These same three wild-type strains bound more vitronectin than did their uspA2 mutants. UspA2 proteins from these three strains, when expressed in Haemophilus influenzae, bound vitronectin and conferred serum resistance on this organism. Furthermore, vitronectin-depleted NHS exhibited bactericidal activity against these same three serum-resistant wild-type strains; addition of purified vitronectin to this serum restored serum resistance. In contrast, binding of the complement regulator C4b-binding protein by the M. catarrhalis strains used in this study was found to be highly variable and did not appear to correlate with the serum-resistant phenotype. These results indicate that binding of vitronectin by UspA2 is involved in the serum resistance of M. catarrhalis; this represents the first example of vitronectin-mediated serum resistance on a microbe. PMID:16495531

Attia, Ahmed S; Ram, Sanjay; Rice, Peter A; Hansen, Eric J

2006-03-01

111

Intranasal Vaccination with Recombinant Outer Membrane Protein CD and Adamantylamide Dipeptide as the Mucosal Adjuvant Enhances Pulmonary Clearance of Moraxella catarrhalis in an Experimental Murine Model  

Microsoft Academic Search

Moraxella catarrhalis causes acute otitis media in children and lower respiratory tract infections in adults and elderly. In children the presence of antibodies against the highly conserved outer membrane protein CD correlates with protection against infection, suggesting that this protein may be useful as a vaccine antigen. However, native CD is difficult to purify, and it is still unclear if

Pablo D. Becker; Gustavo M. Bertot; David Souss; Thomas Ebensen; Carlos A. Guzman; Saul Grinstein

2007-01-01

112

In vitro evaluation of a novel orally administered cephalosporin (cefditoren) tested against 1249 recent clinical isolates of Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae  

Microsoft Academic Search

Cefditoren (formerly ME-1206), a new orally administered cephalosporin, was evaluated in vitro against 1249 recently isolated strains of Streptococcus pneumoniae (500 strains), Moraxella catarrhalis (250 strains), and Haemophilus influenzae (499 strains). Reference National Committee for Clinical Laboratory Standards methods were used and the strains were representative for the current rates of ?-lactamase production or penicillin resistance. Cefditoren had MIC50\\/MIC90 results

Ronald N. Jones; Douglas J. Biedenbach; Matthew A. T. Croco; Mary S. Barrett

1998-01-01

113

Susceptibility trends of haemophilus influenzae and Moraxella catarrhalis against orally administered antimicrobial agents: five-year report from the SENTRY Antimicrobial Surveillance Program  

Microsoft Academic Search

The assessment of orally administered antimicrobial susceptibilities of common pathogens that cause community-acquired respiratory tract infections (CARTI) has become exceedingly important due to the number of office visits for this indication. Numerous local, regional and global studies have documented the susceptibilities of Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis, the most common CARTI pathogens. SENTRY Antimicrobial Surveillance Program sites in

D. M Johnson; H. S Sader; T. R Fritsche; D. J Biedenbach; Ronald N Jones

2003-01-01

114

A conserved tetranucleotide repeat is necessary for wild-type expression of the Moraxella catarrhalis UspA2 protein.  

PubMed

The UspA2 protein has been shown to be directly involved in the serum-resistant phenotype of Moraxella catarrhalis. The predicted 5'-untranslated regions (UTR) of the uspA2 genes in several different M. catarrhalis strains were shown to contain various numbers (i.e., 6 to 23) of a heteropolymeric tetranucleotide (AGAT) repeat. Deletion of the AGAT repeats from the uspA2 genes in the serum-resistant M. catarrhalis strains O35E and O12E resulted in a drastic reduction in UspA2 protein expression and serum resistance. PCR and transformation were used to construct a series of M. catarrhalis O12E strains that differed only in the number of AGAT repeats in their uspA2 genes. Expression of UspA2 was maximal in the presence of 18 AGAT repeats, although serum resistance attained wild-type levels in the presence of as few as nine AGAT repeats. Increased UspA2 expression was correlated with both increased binding of vitronectin and decreased binding of polymerized C9. Real-time reverse transcription-PCR analysis showed that changes in the number of AGAT repeats affected the levels of uspA2 mRNA, with 15 to 18 AGAT repeats yielding maximal levels. Primer extension analysis indicated that these AGAT repeats were contained in the 5'-UTR of the uspA2 gene. The mRNA transcribed from a uspA2 gene containing 18 AGAT repeats was found to have a longer half-life than that transcribed from a uspA2 gene lacking AGAT repeats. These data confirm that the presence of the AGAT repeats in the 5'-UTR of the uspA2 gene is necessary for both normal expression of the UspA2 protein and serum resistance. PMID:16963572

Attia, Ahmed S; Hansen, Eric J

2006-11-01

115

Changes in genetic types and population dynamics of Moraxella catarrhalis in hospitalized children are not associated with an exacerbation of existing disease.  

PubMed

Pulsed-field gel electrophoresis typing was performed on a retrospective set of 129 Moraxella catarrhalis isolates obtained over a 20 month period from 70 children admitted to, or presenting at, the Erasmus University Medical Center, Rotterdam, The Netherlands. The mean age of the children (at the end of the study) was 2.5 years, with a range of 6 months to 15 years. Fifty-one different M. catarrhalis types were isolated from the hospitalized children, with 31 % (22/70) being infected with two particularly prevalent M. catarrhalis types. These two prevalent types also exhibited different protein profiles. The majority (72%; 16/22) of the children infected with these two predominant types had spent at least 1 week on two paediatric intensive care wards. No exacerbation of existing disease or new disease was observed in children who experienced M. catarrhalis type changes. PMID:12909660

Hays, J P; Eadie, K; Verduin, C M; Hazelzet, J; Verbrugh, H; van Belkum, A

2003-09-01

116

The frequency of BRO ?-lactamase and its relationship to antimicrobial susceptibility and serum resistance in Moraxella catarrhalis.  

PubMed

We investigated the frequency of BRO ?-lactamase and its relationship to antibiotic susceptibility profiles and serum susceptibility. Moraxella catarrhalis clinical isolates (n = 197) were collected from patients with respiratory tract infections in Tokyo between November 2004 and April 2005. Phenotypic and genotypic detection of ?-lactamases was performed. The MICs of 6 antibiotics were determined by Etest, and the serum bactericidal assay was conducted by using the culture-and-spot test. Nearly all (192; 97%) of the clinical isolates were ?-lactamase producers; of these, 182 (95%) were bro-1 and 10 (5%) were bro-2 positive. MIC50, MIC90, and geometric mean MICs of penicillin, amoxicillin, cefixime, and clarithromycin for BRO-1 isolates were significantly higher than for BRO-2 isolates. The frequency of intermediate and full serum resistance was significantly higher in BRO-1 isolates than in BRO-2 isolates (P = 0.0056), but not BRO-negative isolates (P = 0.1333). We provide the first evidence that the presence of BRO-1 in M. catarrhalis is associated with reduced susceptibility to clarithromycin and ?-lactam antibiotics, as well as serum non-sensitive (intermediate and resistant). PMID:24462416

Saito, Ryoichi; Nonaka, Shotaro; Fujinami, Yuji; Matsuoka, Shiho; Nakajima, Shinichi; Nishiyama, Hiroyuki; Okamura, Noboru

2014-01-01

117

Roles of 3-Deoxy-d-manno-2-Octulosonic Acid Transferase from Moraxella catarrhalis in Lipooligosaccharide Biosynthesis and Virulence  

PubMed Central

Lipooligosaccharide (LOS), a major outer membrane component of Moraxella catarrhalis, is a possible virulence factor in the pathogenesis of human infections caused by the organism. However, information about the roles of the oligosaccharide chain from LOS in bacterial infection remains limited. Here, a kdtA gene encoding 3-deoxy-d-manno-2-octulosonic acid (Kdo) transferase, which is responsible for adding Kdo residues to the lipid A portion of the LOS, was identified by transposon mutagenesis and construction of an isogenic kdtA mutant in strain O35E. The resulting O35EkdtA mutant produced only lipid A without any core oligosaccharide, and it was viable. Physicochemical and biological analysis revealed that the mutant was susceptible to hydrophobic reagents and a hydrophilic glycopeptide and was sensitive to bactericidal activity of normal human serum. Importantly, the mutant showed decreased toxicity by the Limulus amebocyte lysate assay, reduced adherence to human epithelial cells, and enhanced clearance in lungs and nasopharynx in a mouse aerosol challenge model. These data suggest that the oligosaccharide moiety of the LOS is important for the biological activity of the LOS and the virulence capability of the bacteria in vitro and in vivo. This study may bring new insights into novel vaccines or therapeutic interventions against M. catarrhalis infections.

Peng, Daxin; Choudhury, Biswa P.; Petralia, Ronald S.; Carlson, Russell W.; Gu, Xin-Xing

2005-01-01

118

Colonization of healthy children by Moraxella catarrhalis is characterized by genotype heterogeneity, virulence gene diversity and co-colonization with Haemophilus influenzae.  

PubMed

The colonization dynamics of Moraxella catarrhalis were studied in a population comprising 1079 healthy children living in Rotterdam, The Netherlands (the Generation R Focus cohort). A total of 2751 nasal swabs were obtained during four clinic visits timed to take place at 1.5, 6, 14 and 24 months of age, yielding a total of 709 M. catarrhalis and 621 Haemophilus influenzae isolates. Between January 2004 and December 2006, approximate but regular 6-monthly cycles of colonization were observed, with peak colonization incidences occurring in the autumn/winter for M. catarrhalis, and winter/spring for H. influenzae. Co-colonization was significantly more likely than single-species colonization with either M. catarrhalis or H. influenzae, with genotypic analysis revealing no clonality for co-colonizing or single colonizers of either bacterial species. This finding is especially relevant considering the recent discovery of the importance of H. influenzae-M. catarrhalis quorum sensing in biofilm formation and host clearance. Bacterial genotype heterogeneity was maintained over the 3-year period of the study, even within this relatively localized geographical region, and there was no association of genotypes with either season or year of isolation. Furthermore, chronological and genotypic diversity in three immunologically important M. catarrhalis virulence genes (uspA1, uspA2 and hag/mid) was also observed. This study indicates that genotypic variation is a key factor contributing to the success of M. catarrhalis colonization of healthy children in the first years of life. Furthermore, variation in immunologically relevant virulence genes within colonizing populations, and even within genotypically identical M. catarrhalis isolates, may be a result of immune evasion by this pathogen. Finally, the factors facilitating M. catarrhalis and H. influenzae co-colonization need to be further investigated. PMID:20847012

Verhaegh, Suzanne J C; Snippe, Martine L; Levy, Foster; Verbrugh, Henri A; Jaddoe, Vincent W V; Hofman, Albert; Moll, Henriëtte A; van Belkum, Alex; Hays, John P

2011-01-01

119

EXPRESSION OF THE COPB OUTER MEMBRANE PROTEIN BY MORAXELLA CATARRHALIS IS REGULATED BY IRON AND AFFECTS IRON ACQUISITION FROM TRANSFERRIN AND LACTOFERRIN. ??? 974  

Microsoft Academic Search

The amino acid sequence of the cell-surface-exposed, 81-kDa CopB outer membrane protein of Moraxella catarrhalis was found to be similar to those of TonB-dependent outer membrane proteins of other gram- negative bacteria. Expression of CopB was affected by the availability of iron in the growth medium, and the extent of overexpression of CopB in response to iron limitation varied widely

Christoph Aebi; Barbara Stone; Margaret Beucher; Leslie D. Cope; Isobel Maciver; Sharon E. Thomas; P. Frederick Sparling; Eric J. Hansen

1996-01-01

120

Surveillance of antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the United States in 1996–1997 respiratory season  

Microsoft Academic Search

A U.S. surveillance study of antimicrobial resistance in respiratory tract pathogens in the respiratory season (1996–1997) is reported that induced 11,368 isolates from 434 institutions in 45 states and the District of Columbia. ?-lactamase was produced by 33.4% of Haemophilus influenzae and 92.7% of Moraxella catarrhalis. Of the 9,190 Streptococcus pneumoniae isolates tested, 33.5% were not susceptible to penicillin (MIC

Clyde Thornsberry; Penny Ogilvie; James Kahn; Yolanda Mauriz

1997-01-01

121

The outer membrane proteins UspA1 and UspA2 of Moraxella catarrhalis are highly conserved in nasopharyngeal isolates from young children  

Microsoft Academic Search

UspA1 and UspA2 of Moraxella catarrhalis are vaccine candidates. The aims of this study were to determine: (1) the frequencies of occurrence and (2) the degrees of conservation of two surface-exposed epitopes of the uspA1 and uspA2 genes and their respective gene products in 108 nasopharyngeal isolates from young children. The uspA1 and uspA2 genes were detected in 107 (99%)

Patricia Stutzmann Meier; Rolf Troller; Ioanna N. Grivea; George A. Syrogiannopoulos; Christoph Aebi

2002-01-01

122

Survey of Susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis Isolates to 26 Antimicrobial Agents: a Prospective U.S. Study  

Microsoft Academic Search

An antimicrobial susceptibility surveillance study of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolates was performed during the winter of 1996-1997 in order to determine their susceptibilities to 5 fluoroquinolones and 21 other antimicrobial agents. Broth microdilution MICs were determined for 2,752 isolates from 51 U.S. medical centers. Of the 1,276 S. pneumoniae isolates, 64% were susceptible, 17% were intermediate,

C. THORNSBERRY; P. T. OGILVIE; H. P. HOLLEY; D. F. SAHM

123

Effect of inoculum size on the in-vitro susceptibility to  -lactam antibiotics of Moraxella catarrhalis isolates of different  -lactamase types  

Microsoft Academic Search

Summary. The effect of inoculum size on the results of agar dilution MIC tests was assessed for 20 Moraxella catarrhalis isolates with BRO-1 enzyme, 20 with BRO-2 enzyme and 15 isolates that did not produce p-lactamase. The compounds tested were ampicillin, co- amoxiclav, cefaclor, cefixime and cefetamet, and the inocula were lo4, lo5, lo6 and lo7 cfu\\/spot. The MICs of

S. F. Yeo; D. M. Livermore

1994-01-01

124

Genesis of BRO beta-lactamase-producing Moraxella catarrhalis: evidence for transformation-mediated horizontal transfer.  

PubMed

The dramatic rise in BRO-producing M. catarrhalis strains observed in the last decades is without precedence. The aim of this study was to elucidate the events that led to the emergence of BRO-1 and BRO-2 beta-lactamases. Previously, we showed bro1 and bro2 to be >99% identical. Data presented here suggested that bro2 was acquired by a fortuitous event and inserted between M. catarrhalis genes orf1 and orf3. Subsequently, bro1 evolved from bro2. Promoter-up mutations increased fitness of bro2, explaining its present predominance. The highly conserved nature of bro compared with orf1 and orf3 suggested that acquisition has occurred relatively recently. The random distribution of bro among M. catarrhalis fingerprint types indicated that bro has spread by horizontal transfer. Sequence analysis revealed that 80-200 bp is generally cotransferred with bro, serving as regions of homology that target bro to the same chromosomal locus. A region of 160 bases upstream of bro1 lacked polymorphism, indicating it was derived from the original strain that acquired bro2. We observed that bro was readily transferred by transformation between M. catarrhalis strains in vitro, suggesting a mechanism by which bro has disseminated. In conclusion, we have been able to reconstruct the steps that led to the emergence of BRO-producing M. catarrhalis. PMID:10760166

Bootsma, H J; van Dijk, H; Vauterin, P; Verhoef, J; Mooi, F R

2000-04-01

125

Comparative analysis and supragenome modeling of twelve Moraxella catarrhalis clinical isolates  

PubMed Central

Background M. catarrhalis is a gram-negative, gamma-proteobacterium and an opportunistic human pathogen associated with otitis media (OM) and exacerbations of chronic obstructive pulmonary disease (COPD). With direct and indirect costs for treating these conditions annually exceeding $33 billion in the United States alone, and nearly ubiquitous resistance to beta-lactam antibiotics among M. catarrhalis clinical isolates, a greater understanding of this pathogen's genome and its variability among isolates is needed. Results The genomic sequences of ten geographically and phenotypically diverse clinical isolates of M. catarrhalis were determined and analyzed together with two publicly available genomes. These twelve genomes were subjected to detailed comparative and predictive analyses aimed at characterizing the supragenome and understanding the metabolic and pathogenic potential of this species. A total of 2383 gene clusters were identified, of which 1755 are core with the remaining 628 clusters unevenly distributed among the twelve isolates. These findings are consistent with the distributed genome hypothesis (DGH), which posits that the species genome possesses a far greater number of genes than any single isolate. Multiple and pair-wise whole genome alignments highlight limited chromosomal re-arrangement. Conclusions M. catarrhalis gene content and chromosomal organization data, although supportive of the DGH, show modest overall genic diversity. These findings are in stark contrast with the reported heterogeneity of the species as a whole, as wells as to other bacterial pathogens mediating OM and COPD, providing important insight into M. catarrhalis pathogenesis that will aid in the development of novel therapeutic regimens.

2011-01-01

126

Moraxella catarrhalis strains with reduced expression of the UspA outer membrane proteins belong to a distinct subpopulation.  

PubMed

The outer membrane proteins UspA1 and UspA2 are candidate antigens for a Moraxella catarrhalis vaccine. We previously reported that 103 of 108 isolates (95%) from young children expressed UspA1 detected by reactivity with the monoclonal antibody mAb24B5. The aim of the present study was to investigate mechanisms controlling UspA1 expression by analysis of five mAb24B5 non-reactive isolates. Four of these strains were characterized by (i) decreased or absent transcription of uspA1 and uspA2 and (ii) clustered mutations and deletions in the promoter region of both uspA1 and uspA2. Antigenic or phase variation were not responsible for reduced levels of UspA1 expression. While mAb24B5-positive isolates expressing normal levels of uspA1 and uspA2 mRNA belonged to the previously described 16S rRNA type 1 phylogenetic group, these four mAb24B5-negative isolates were found to belong to the 16S rRNA gene types 2 or 3. The remaining mAb24B5-negative isolate (#610) belonged to 16S rRNA type 1 and exhibited a posttranscriptional defect of UspA1 expression defined by normal levels of uspA1 mRNA and both recombinant and in vitro expression of mAb24B5-reactive UspA1. In conclusion, M. catarrhalis clinical isolates exhibiting reduced expression of UspA1 and UspA2 belonged to a distinct phylogenetic subpopulation. A UspA-based vaccine is unlikely to be effective against such isolates. PMID:15734074

Meier, Patricia Stutzmann; Troller, Rolf; Heiniger, Nadja; Grivea, Ioanna N; Syrogiannopoulos, George A; Aebi, Christoph

2005-03-14

127

Use of the Chinchilla model to evaluate the vaccinogenic potential of the Moraxella catarrhalis filamentous hemagglutinin-like proteins MhaB1 and MhaB2.  

PubMed

Moraxella catarrhalis causes significant health problems, including 15-20% of otitis media cases in children and ~10% of respiratory infections in adults with chronic obstructive pulmonary disease. The lack of an efficacious vaccine, the rapid emergence of antibiotic resistance in clinical isolates, and high carriage rates reported in children are cause for concern. In addition, the effectiveness of conjugate vaccines at reducing the incidence of otitis media caused by Streptococcus pneumoniae and nontypeable Haemophilus influenzae suggest that M. catarrhalis infections may become even more prevalent. Hence, M. catarrhalis is an important and emerging cause of infectious disease for which the development of a vaccine is highly desirable. Studying the pathogenesis of M. catarrhalis and the testing of vaccine candidates have both been hindered by the lack of an animal model that mimics human colonization and infection. To address this, we intranasally infected chinchilla with M. catarrhalis to investigate colonization and examine the efficacy of a protein-based vaccine. The data reveal that infected chinchillas produce antibodies against antigens known to be major targets of the immune response in humans, thus establishing immune parallels between chinchillas and humans during M. catarrhalis infection. Our data also demonstrate that a mutant lacking expression of the adherence proteins MhaB1 and MhaB2 is impaired in its ability to colonize the chinchilla nasopharynx, and that immunization with a polypeptide shared by MhaB1 and MhaB2 elicits antibodies interfering with colonization. These findings underscore the importance of adherence proteins in colonization and emphasize the relevance of the chinchilla model to study M. catarrhalis-host interactions. PMID:23844117

Shaffer, Teresa L; Balder, Rachel; Buskirk, Sean W; Hogan, Robert J; Lafontaine, Eric R

2013-01-01

128

Use of an Isogenic Mutant Constructed in Moraxella catarrhalis To Identify a Protective Epitope of Outer Membrane Protein B1 Defined by Monoclonal Antibody 11C6  

PubMed Central

Moraxella catarrhalis-induced otitis media continues to be a significant cause of infection in young children, prompting increased efforts at identifying effective vaccine antigens. We have previously demonstrated that M. catarrhalis expresses specific outer membrane proteins (OMPs) in response to iron limitation and that this organism can utilize transferrin and lactoferrin for in vitro growth. One of these proteins, which binds human transferrin, is OMP B1. As the human host presents a naturally iron-limited environment, proteins, like OMP B1, which are expressed in response to this nutritional stress are potential vaccine antigens. In this study, we have developed monoclonal antibody (MAb) 11C6, which reacts to a surface-exposed epitope of OMP B1 expressed by M. catarrhalis 7169. This antibody was used to clone ompB1, and sequence analysis suggested that OMP B1 is the M. catarrhalis homologue to the transferrin binding protein B described for pathogenic Neisseriaceae, Haemophilus influenzae, Actinobacillus pleuropneumoniae, and M. catarrhalis. Expression of recombinant OMP B1 on the surface of Escherichia coli confers transferrin binding activity, confirming that this protein is likely involved in iron acquisition. In addition, ompB1 was used to construct an isogenic mutant in M. catarrhalis 7169. This mutant, termed 7169b12, was used as the control in bactericidal assays designed to determine if OMP B1 elicits protective antibodies. In the presence of MAb 11C6 and human complement, wild-type 7169 demonstrated a 99% decline in viability, whereas the ompB1 isogenic mutant was resistant to this bactericidal activity. Further analysis with MAb 11C6 revealed the presence of this OMP B1 epitope on 31% of the clinical isolates tested. These data suggest that OMP B1 is a potential vaccine antigen against M. catarrhalis infections.

Luke, Nicole R.; Russo, Thomas A.; Luther, Neal; Campagnari, Anthony A.

1999-01-01

129

Biochemical and immunological properties of lactoferrin binding proteins from Moraxella (Branhamella) catarrhalis  

Microsoft Academic Search

The Neisseriaceae can acquire iron (Fe) from lactoferrin (Lf) using host-Lf receptors on the bacterial surface. The binding proteins that are proposed to constitute the receptor have been identified by isolation with immobilized Lf. Using CopB-specific monoclonal antibodies and isogenic CopB mutants, we demonstrate that the 84 kDa protein isolated with immobilized human Lf fromMoraxella catarrhalisusing low stringency conditions is

Robert A Bonnah; Rong-Hua Yu; Henry Wong; Anthony B Schryvers

1998-01-01

130

A Novel Group of Moraxella catarrhalis UspA Proteins Mediates Cellular Adhesion via CEACAMs and Vitronectin  

PubMed Central

Moraxella catarrhalis (Mx) is a common cause of otitis media and exacerbation of chronic obstructive pulmonary disease, an increasing worldwide problem. Surface proteins UspA1 and UspA2 of Mx bind to a number of human receptors and may function in pathogenesis. Genetic recombination events in the pathogen can generate hybrid proteins termed UspA2H. However, whether certain key functions (e.g. UspA1-specific CEACAM binding) can be exchanged between these adhesin families remains unknown. In this study, we have shown that Mx can incorporate the UspA1 CEACAM1-binding region not only into rare UspA1 proteins devoid of CEACAM-binding ability, but also into UspA2 which normally lack this capacity. Further, a screen of Mx isolates revealed the presence of novel UspA2 Variant proteins (UspA2V) in ?14% of the CEACAM-binding population. We demonstrate that the expression of UspA2/2V with the CEACAM-binding domain enable Mx to bind both to cell surface CEACAMs and to integrins, the latter via vitronectin. Such properties of UspA2/2V have not been reported to date. The studies demonstrate that the UspA family is much more heterogeneous than previously believed and illustrate the in vivo potential for exchange of functional regions between UspA proteins which could convey novel adhesive functions whilst enhancing immune evasion.

Hill, Darryl J.; Whittles, Cheryl; Virji, Mumtaz

2012-01-01

131

Activity of cefditoren against ?-lactamase-positive and -negative Haemophilus influenzae and Moraxella catarrhalis  

Microsoft Academic Search

Cefditoren is a novel broad-spectrum oral cephalosporin. To determine the influence of ?-lactamase production on cefditoren activity, 1,170 H. influenzae and 641 M. catarrhalis isolated during 2000 were tested by NCCLS broth microdilution methodology (M7-A5, 2000). Against H. influenzae the potency of cefditoren (MIC90, 0.015 ?g\\/mL) was similar to that of ceftriaxone (MIC90, ?0.015 ?g\\/mL) and levofloxacin (MIC90, 0.015 ?g\\/mL),

James A. Karlowsky; Ian A. Critchley; Deborah C. Draghi; Mark E. Jones; Clyde Thornsberry; Daniel F. Sahm

2002-01-01

132

The Moraxella catarrhalis Immunoglobulin D-Binding Protein MID Has Conserved Sequences and Is Regulated by a Mechanism Corresponding to Phase Variation  

PubMed Central

The prevalence of the Moraxella catarrhalis immunoglobulin D (IgD)-binding outer membrane protein MID and its gene was determined in 91 clinical isolates and in 7 culture collection strains. Eighty-four percent of the clinical Moraxella strains expressed MID-dependent IgD binding. The mid gene was detected in all strains as revealed by homology of the signal peptide sequence and a conserved area in the 3? end of the gene. When MID proteins from five different strains were compared, an identity of 65.3 to 85.0% and a similarity of 71.2 to 89.1% were detected. Gene analyses showed several amino acid repeat motifs in the open reading frames, and MID could be called a putative autotransport protein. Interestingly, homopolymeric {polyguanine [poly(G)]} tracts were detected at the 5? ends within the open reading frames. By flow cytometry, using human IgD and fluorescein isothiocyanate-conjugated anti-IgD polyclonal antibodies, most strains showed two peaks: one high- and one low-intensity peak. All isolates expressing high levels of MID had 1, 2, or 3 triplets of G's in their poly(G) tracts, while strains not expressing MID had 4, 7, 8, or 10 G’s in their poly(G) tracts or point mutations causing a putative preterminated translation. Northern blot analysis revealed that the mid gene was regulated at the transcriptional level. Experiments with nonclumping variants of M. catarrhalis proved that bacteria lost their MID expression by removing a G in their poly(G) tracts. Moraxella strains isolated from the nasopharynx or from blood and sputum specimens expressed MID at approximately the same frequency. In addition, no variation was observed between strains of different geographical origins (Australia, Europe, Japan, or the United States). MID and the mid gene were found solely in M. catarrhalis, whereas related Neisseria and Moraxella species did not express MID. Taken together, MID appears to be a conserved protein that can be found in essentially all M. catarrhalis strains. Furthermore, MID is governed by poly(G) tracts when bacteria undergo phase variation.

Mollenkvist, Andrea; Nordstrom, Therese; Hallden, Christer; Christensen, Jens J?rgen; Forsgren, Arne; Riesbeck, Kristian

2003-01-01

133

Antimicrobial activity and in vitro susceptibility test development for cefditoren against Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus species.  

PubMed

Cefditoren, a third generation orally administered aminothiazolyl cephalosporin, has demonstrated bactericidal activity against many Gram positive and negative bacterial pathogens and stability against clinically important beta-lactamases. Cefditoren was compared to cefaclor, cefixime, and penicillins against 1 435 recently isolated strains of streptococci (312 Streptococcus pneumoniae, 165 viridans group streptococci, 142 beta-haemolytic streptococci), Haemophilus influenzae (521 strains), and Moraxella catarrhalis (295 strains). Streptococcus pneumoniae and viridans group streptococci had penicillin nonsusceptible rates of 37.8 and 35.8%, respectively. Cefditoren (MIC(90) in microg/ml/% susceptible) activity against all tested H. influenzae (0.03/100) and M. catarrhalis (0.06-0.5/100) was comparable to cefixime and significantly greater than cefaclor. Cefditoren (MIC(90), 0.5 microg/ml) was 4- to 128-fold more active than comparison beta-lactams against the pneumoococci and was the most potent beta-lactam (including penicillin) versus beta-haemolytic streptococci. Cefditoren pharmacokinetics demonstrate a T(1/2) of 1.5-2 h and C(max) values of 2.8 and 4.6 microg/ml, respectively with 200 or 400 mg doses of cefditoren pivoxil; plasma concentrations exceed 1 microg/ml for 4 to 6 hours (33-50% of dosing interval). Consequently, a susceptible MIC of /= 18 and >/= 15 mm (5-microg disk) for all cited fastidious species tested. Categorical agreement between MIC and disk tests was 94.6 to 100% with a correlation coefficient (r) range of 0.50 to 0.90 for streptococci. H. influenzae intermethod comparison results using the same interpretive criteria were in complete agreement, but exhibited a low r = 0.39. Cefditoren clearly possesses the most potent activity among currently studied oral cephalosporins or penicillin against commonly isolated bacterial pathogens causing bronchitis, pneumonia, sinusitis, or pharyngitis and was active against nearly all penicillin-resistant streptococci at

Johnson, D M; Biedenbach, D J; Beach, M L; Pfaller, M A; Jones, R N

2000-06-01

134

A novel group of Moraxella catarrhalis UspA proteins mediates cellular adhesion via CEACAMs and vitronectin.  

PubMed

Moraxella catarrhalis (Mx) is a common cause of otitis media and exacerbation of chronic obstructive pulmonary disease, an increasing worldwide problem. Surface proteins UspA1 and UspA2 of Mx bind to a number of human receptors and may function in pathogenesis. Genetic recombination events in the pathogen can generate hybrid proteins termed UspA2H. However, whether certain key functions (e.g. UspA1-specific CEACAM binding) can be exchanged between these adhesin families remains unknown. In this study, we have shown that Mx can incorporate the UspA1 CEACAM1-binding region not only into rare UspA1 proteins devoid of CEACAM-binding ability, but also into UspA2 which normally lack this capacity. Further, a screen of Mx isolates revealed the presence of novel UspA2 Variant proteins (UspA2V) in ?14% of the CEACAM-binding population. We demonstrate that the expression of UspA2/2V with the CEACAM-binding domain enable Mx to bind both to cell surface CEACAMs and to integrins, the latter via vitronectin. Such properties of UspA2/2V have not been reported to date. The studies demonstrate that the UspA family is much more heterogeneous than previously believed and illustrate the in vivo potential for exchange of functional regions between UspA proteins which could convey novel adhesive functions whilst enhancing immune evasion. PMID:23049802

Hill, Darryl J; Whittles, Cheryl; Virji, Mumtaz

2012-01-01

135

Age-related genotypic and phenotypic differences in Moraxella catarrhalis isolates from children and adults presenting with respiratory disease in 2001-2002.  

PubMed

Moraxella catarrhalis is generally associated with upper respiratory tract infections in children and lower respiratory tract infections in adults. However, little is known regarding the population biology of isolates infecting these two age groups. To address this, a population-screening strategy was employed to investigate 195 worldwide M. catarrhalis isolates cultured from children (<5 years of age) and adults (>20 years of age) presenting with respiratory disease in the years 2001-2002. Parameters compared included: genotype analysis; autoagglutination/biofilm-forming ability; serum resistance; uspA1, uspA2, uspA2H, hag and mcaP incidence; copB/LOS/ompCD/16S rRNA types; and UspA1/Hag expression. A significant difference in biofilm formation (P=0.002), but not in autoagglutination or serum resistance, was observed, as well as significant differences in the incidence of uspA2- and uspA2H-positive isolates, and the distribution of lipooligosaccharide (LOS) types (P<0.0001 and P=0.01, respectively). Further, a significant decrease in the incidence of Hag expression (for isolates possessing the hag gene) was observed in adult isolates (P=0.001). Both uspA2H and LOS type B were associated with 16S rRNA type 1 isolates only, and two surrogate markers (copB and ompCD PCR RFLP types) for the two major M. catarrhalis 16S rRNA genetic lineages were identified. In conclusion, there are significant differences in phenotype and gene incidence between M. catarrhalis isolates from children and adults presenting with respiratory disease, possibly as a result of immune evasion in the adult age group. Our results should also be useful in the choice of effective vaccine candidates against M. catarrhalis. PMID:18375810

Verhaegh, Suzanne J C; Streefland, André; Dewnarain, Joy K; Farrell, David J; van Belkum, Alex; Hays, John P

2008-04-01

136

Regional Trends in Antimicrobial Resistance among Clinical Isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the United States: Results from the TRUST Surveillance Program, 1999–2000  

Microsoft Academic Search

The ongoing TRUST (Tracking Resistance in the United States Today) study, which began monitoring anti- microbial resistance among respiratory pathogens in 1996, routinely tracks resistance at national and regional levels. The 1999-2000 TRUST study analyzed 9499 Streptococcus pneumoniae, 1934 Haemophilus influenzae, and 1108 Moraxella catarrhalis isolates that were prospectively collected from 239 laboratories across the 9 US Bureau of the

Clyde Thornsberry; Daniel F. Sahm; Laurie J. Kelly; Ian A. Critchley; Mark E. Jones; Alan T. Evangelista; James A. Karlowsky

2002-01-01

137

High-throughput amplification fragment length polymorphism (htAFLP) analysis identifies genetic lineage markers but not complement phenotype-specific markers in Moraxella catarrhalis.  

PubMed

Comparative high-throughput amplified fragment length polymorphism (htAFLP) analysis was performed on a set of 25 complement-resistant and 23 complement-sensitive isolates of Moraxella catarrhalis in order to determine whether there were complement phenotype-specific markers within this species. The htAFLP analysis used 21 primer-pair combinations, generating 41 364 individual fragments and 2273 fragment length polymorphisms, with an average of 862 polymorphisms per isolate. Analysis of polymorphism data clearly indicated the presence of two phylogenetic lineages and 40 (2%) lineage-specific polymorphisms. However, despite the presence of 361 (16%) statistically significant complement phenotype-associated polymorphisms, no single marker was 100% complement phenotype-specific. Furthermore, no complement phenotype-specific marker was found within different phylogenetic lineages. These findings agree with previous results indicating that the complement resistance phenotype within M. catarrhalis is probably defined by multiple genes, although not all of these genes may be present within all M. catarrhalis isolates. PMID:17184288

Hays, J P; Gorkink, R; Simons, G; Peeters, J K; Eadie, K; Verduin, C M; Verbrugh, H; van Belkum, A

2007-01-01

138

Susceptibility of Moraxella catarrhalis to 21 antimicrobial drugs: validity of current NCCLS criteria for the interpretation of agar disk diffusion antibiograms.  

PubMed

Ninety-four clinical isolates of Moraxella catarrhalis were examined for susceptibility to 21 antimicrobial drugs; 67 isolates (= 71.3%) produced beta-lactamase(s). In terms of antibiotic resistance, the number of isolates resistant to penicillin G, ampicillin, and cotrimoxazole were 56, 32, and 1, respectively. The number of isolates with intermediate susceptibility to penicillin G, ampicillin, ciprofloxacin, ofloxacin, cotrimoxazole, and fosfomycin were 11, 34, 1, 2, 2, and 47, respectively. All 94 isolates proved susceptible to ampicillin + 10 micrograms/ml of sulbactam, amoxicillin + 4 micrograms/ml of clavulanic acid, cefuroxime, cefotaxime, cefepime, cefepime, cefixime, imipenem, meropenem, chloramphenicol, doxycycline, tetracycline, fusidic acid, erythromycin, clarithromycin, and rifampin, as based on currently valid NCCLS criteria, where applicable. There were no very major or major discrepancies between agar dilution and agar disk diffusion test results. There were only a few minor discrepancies between test results, specifically: penicillin G (category IV = 4, category VI = 1); ampicillin (category IV = 4, category V = 1, category VI = 7), amoxicillin + clavulanic acid (category III = 11), cotrimoxazole (category IV = 1, category V = 1, category VI = 1), ciprofloxacin (category V = 1), and ofloxacin (category VI = 2). The sole exception was fosfomycin, with a total of 25 minor discrepancies encountered (category III = 14, category V = 9, category VI = 2). Wilkins-Chalgren agar compared favorably with Mueller-Hinton agar following examination with 11 selected antimicrobial drugs against 31 representative isolates of M. catarrhalis. PMID:9142455

Traub, W H; Leonhard, B

1997-01-01

139

In vitro activity of BAY 12-8039, a novel 8-methoxyquinolone, compared to activities of six fluoroquinolones against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.  

PubMed Central

The in vitro activity of a novel 8-methoxyquinolone, BAY 12-8039, against recent clinical isolates of Streptococcus pneumoniae (n = 404), Haemophilus influenzae (n = 330), and Moraxella catarrhalis (n = 250) was evaluated. Activity was compared to those of six other fluoroquinolones: ciprofloxacin, clinafloxacin, levofloxacin, ofloxacin, sparfloxacin and trovafloxacin. BAY 12-8039 and clinafloxacin had the highest levels of activity against S. pneumoniae, both with a MIC at which 90% of the isolates were inhibited (MIC90) of 0.06 microg/ml. Trovafloxacin and sparfloxacin were the next most active agents versus S. pneumoniae (MIC90s = 0.12 microg/ml). No differences in activity against penicillin-susceptible, -intermediate, or -resistant strains of S. pneumoniae were noted for any of the fluoroquinolones tested. MIC90s for the seven fluoroquinolones ranged from 0.008 to 0.06 microg/ml versus H. influenzae and from 0.008 to 0.12 microg/ml for M. catarrhalis. The MICs for two strains of S. pneumoniae and one strain of H. influenzae were noted to be higher than those for the general population of organisms for all of the fluoroquinolones tested. Finally, the activity of BAY 12-8039 versus S. pneumoniae was found to be diminished when MIC determinations were performed with incubation of agar dilution plates or broth microdilution trays in 5 to 7% CO2 versus ambient air.

Brueggemann, A B; Kugler, K C; Doern, G V

1997-01-01

140

Association of Gm allotypes with the antibody response to the outer membrane proteins of a common upper respiratory tract organism, Moraxella catarrhalis.  

PubMed

Previously, Gm allotypes have been shown to influence human serum Ig subclass levels as well as the Ab levels achieved after Ag stimulation. The majority of the latter studies have focused on Ab responses to polysaccharide Ags. In this study, we have investigated the relationship between Gm allotypes and naturally occurring serum Ab levels to a bacterial protein Ag, the outer membrane proteins of a common microorganism, Moraxella catarrhalis. In the sera of 160 patients having chronic/recurrent sinusitis, there was a highly significant correlation between the level of specific anti-M. catarrhalis IgG3 level and certain Gm phenotypes. After additional investigation, we found that the presence of G3m(21) homozygosity correlated significantly with lower levels of Ag-specific IgG3. Specific anti-M. catarrhalis IgG3 levels were found to be independent of total serum IgG3 concentrations, and there was no correlation between the serum level of IgG3 and any Gm phenotype. Total IgG and IgG2 that were specific for pneumococcal cell wall polysaccharide also were measured in this group of patients, and no correlation was found between the naturally occurring IgG2 subclass levels to pneumococcal cell wall polysaccharide and the interactive effect of G2m(23) (syn: G2m(n)) and Km(1). Gm allotypes may influence Ab responses other than the anti-carbohydrate responses and, therefore, should be taken into account when investigating IgG subclass responses to protein Ags. PMID:7963583

Goldblatt, D; Scadding, G K; Lund, V J; Wade, A M; Turner, M W; Pandey, J P

1994-12-01

141

The Levels and Bactericidal Capacity of Antibodies Directed against the UspA1 and UspA2 Outer Membrane Proteins of Moraxella (Branhamella) catarrhalis in Adults and Children  

Microsoft Academic Search

The UspA1 and UspA2 proteins from Moraxella catarrhalis share antigenic epitopes and are promising vaccine candidates. In this study, the levels and bactericidal activities of antibodies in sera from healthy adults and children toward UspA1 and UspA2 from the O35E strain were measured. Human sera contained anti- bodies to both proteins, and the levels of immunoglobulin G (IgG) antibodies were

DEXIANG CHEN; VICKI BARNIAK; KARL R. VANDERMEID; JOHN C. MCMICHAEL

1999-01-01

142

Moraxella catarrhalis adhesin UspA1-derived recombinant fragment rD-7 induces monocyte differentiation to CD14+CD206+ phenotype.  

PubMed

Circulating monocytes in the bloodstream typically migrate to other tissues and differentiate into tissue resident macrophages, the process being determined by the constituents of the microenvironments encountered. These may include microbes and their products. In this study, we investigated whether Moraxella catarrhalis Ubiquitous Surface Protein A1 (UspA1), known to bind to a widely expressed human cell surface receptor CEACAM1, influences monocyte differentiation as receptor engagement has been shown to have profound effects on monocytes. We used the recombinant molecules corresponding to the regions of UspA1 which either bind (rD-7; UspA1527-665) or do not bind (r6-8; UspA1659-863) to CEACAM1 and investigated their effects on CD206, CD80 and CD86 expression on freshly isolated human CD14+ monocytes from peripheral blood mononuclear cells (PBMC). Exposure to rD-7, but not r6-8, biased monocyte differentiation towards a CD14+CD206+ phenotype, with reduced CD80 expression. Monocytes treated with rD-7 also secreted high levels of IL-1ra and chemokine IL-8 but not IL-10 or IL-12p70. The effects of rD-7 were independent of any residual endotoxin. Unexpectedly, these effects of rD-7 were also independent of its ability to bind to CEACAM1, as monocyte pre-treatment with the anti-CEACAM antibody A0115 known to inhibit rD-7 binding to the receptor, did not affect rD-7-driven differentiation. Further, another control protein rD-7/D (a mutant form of rD-7, known not to bind to CEACAMs), also behaved as the parent molecule. Our data suggest that specific regions of M. catarrhalis adhesin UspA1 may modulate inflammation during infection through a yet unknown receptor on monocytes. PMID:24599281

Xie, Qi; Brackenbury, Louise S; Hill, Darryl J; Williams, Neil A; Qu, Xun; Virji, Mumtaz

2014-01-01

143

Correlation of in situ mechanosensitive responses of the Moraxella catarrhalis adhesin UspA1 with fibronectin and receptor CEACAM1 binding.  

PubMed

Bacterial cell surfaces are commonly decorated with a layer formed from multiple copies of adhesin proteins whose binding interactions initiate colonization and infection processes. In this study, we investigate the physical deformability of the UspA1 adhesin protein from Moraxella catarrhalis, a causative agent of middle-ear infections in humans. UspA1 binds a range of extracellular proteins including fibronectin, and the epithelial cellular receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Electron microscopy indicates that unliganded UspA1 is densely packed at, and extends about 800 ? from, the Moraxella surface. Using a modified atomic force microscope, we show that the adhesive properties and thickness of the UspA1 layer at the cell surface varies on addition of either fibronectin or CEACAM1. This in situ analysis is then correlated with the molecular structure of UspA1. To provide an overall model for UspA1, we have determined crystal structures for two N-terminal fragments which are then combined with a previous structure of the CEACAM1-binding site. We show that the UspA1-fibronectin complex is formed between UspA1 head region and the 13th type-III domain of fibronectin and, using X-ray scattering, that the complex involves an angular association between these two proteins. In combination with a previous study, which showed that the CEACAM1-UspA1 complex is distinctively bent in solution, we correlate these observations on isolated fragments of UspA1 with its in situ response on the cell surface. This study therefore provides a rare direct demonstration of protein conformational change at the cell surface. PMID:21876142

Agnew, Christopher; Borodina, Elena; Zaccai, Nathan R; Conners, Rebecca; Burton, Nicholas M; Vicary, James A; Cole, David K; Antognozzi, Massimo; Virji, Mumtaz; Brady, R Leo

2011-09-13

144

A fluorescent multiplexed bead-based immunoassay (FMIA) for quantitation of IgG against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis protein antigens.  

PubMed

Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are pathogens commonly associated with infectious diseases in childhood. This study aimed to develop a fluorescent multiplexed bead-based immunoassay (FMIA) using recombinant proteins for the quantitation of serum IgG antibodies against these bacteria. Eight pneumococcal proteins (Ply, CbpA, PspA1, PspA2, PcpA, PhtD, SP1732-3 and SP2216-1), 3 proteins of H. influenzae (NTHi Protein D, NTHi0371-1, NTHi0830), and 5 proteins of M. catarrhalis (MC Omp CD, MC_RH4_2506, MC_RH4_1701, MC_RH4_3729-1, MC_RH4_4730) were used to develop the FMIA. Optimal coupling concentrations for each protein, comparison of singleplex and multiplex assays, specificity, reproducibility, and correlation to ELISA for six pneumococcal antigens were determined for validation. FMIA was then used to analyze acute and convalescent paired serum samples of 50 children with non-severe pneumonia. The coupling concentrations varied for different antigens, ranging from 1.6 to 32?g of protein/million beads. Correlation between singleplexed and multiplexed assays was excellent, with R?0.987. The FMIA was specific, reaching >92% homologous inhibition for all specificities; heterologous inhibition ?20% was found only in six cases. The assay was repeatable, with averages of intra-assay variation ?10.5%, day-to-day variation ?9.7% and variation between technicians ?9.1%. Comparison with ELISA for pneumococcal antigens demonstrated good correlation with R ranging from 0.854 (PspA2) to 0.976 (PcpA). The samples from children showed a wide range of antibody concentrations and increases in convalescent samples. In conclusion, the FMIA was sensitive, specific, and repeatable, using small amounts of recombinant proteins and sera to detect antibodies against S. pneumoniae, H. influenzae and M. catarrhalis. The methodology would be suitable for studies investigating etiological diagnosis and in experimental vaccine studies. PMID:24530690

Andrade, Dafne C; Borges, Igor C; Laitinen, Hanna; Ekström, Nina; Adrian, Peter V; Meinke, Andreas; Barral, Aldina; Nascimento-Carvalho, Cristiana M; Käyhty, Helena

2014-03-01

145

Susceptibilities of Haemophilus influenzae and Moraxella catarrhalis to ABT-773 Compared to Their Susceptibilities to 11 Other Agents  

Microsoft Academic Search

The activity of the ketolide ABT-773 against Haemophilus and Moraxella was compared to those of 11 other agents. Against 210 Haemophilus influenzae strains (39.0% b-lactamase positive), microbroth dilution tests showed that azithromycin and ABT-773 had the lowest MICs (0.5 to 4.0 and 1.0 to 8.0 mg\\/ml, respectively), followed by clarithromycin and roxithromycin (4.0 to >32.0 mg\\/ml). Of the b-lactams, ceftriaxone

KIM L. CREDITO; GENGRONG LIN; GLENN A. PANKUCH; SARALEE BAJAKSOUZIAN; MICHAEL R. JACOBS; PETER C. APPELBAUM

2001-01-01

146

Deciphering the genetic basis of Moraxella catarrhalis complement resistance: a critical role for the disulphide bond formation system.  

PubMed

The complement system is an important innate defence mechanism, and the ability to resist complement-mediated killing is considered a key virulence trait of the respiratory tract pathogen M.?catarrhalis. We studied the molecular basis of complement resistance by transcriptional profiling and Tn-seq, a genome-wide negative-selection screenings technology. Exposure of M.?catarrhalis to human serum resulted in increased expression of 84 genes and reduced expression of 134 genes, among which genes encoding ABC transporter systems and surface proteins UspA1 and McaP. By subjecting a ? 15?800 transposon mutant library to serum, mutants of 53 genes were negatively selected, including the key complement-resistance factor uspA2H. Validation with directed mutants confirmed Tn-seq phenotypes of uspA2H and 11 newly identified genes, with mutants of MCR_0424, olpA, MCR_1483, and dsbB most severely attenuated. Detailed analysis showed that both components of the disulphide bond formation (DSB) system, DsbB and DsbA, were required for complement-resistance in multiple isolates, and fulfil a critical role in evasion of IgG-dependent classical pathway-mediated killing. Lipooligosaccharide (LOS) structure and membrane stability were severely affected in ?dsbA strains, suggesting a pivotal role for the DSB system in LOS structure safeguarding and membrane stability maintenance. PMID:24344868

de Vries, Stefan P W; Rademakers, Rob J A; van der Gaast-de Jongh, Christa E; Eleveld, Marc J; Hermans, Peter W M; Bootsma, Hester J

2014-02-01

147

Usefulness of gram-stained sputum obtained just after administration of antimicrobial agents as the earliest therapeutic indicator for evaluating the effectiveness of empiric therapy in community-acquired pneumonia caused by pneumococcus or Moraxella catarrhalis.  

PubMed

We present here three cases in which morphological changes and/or a decreased number of Streptococcus pneumoniae or Moraxella catarrhalis could be observed in gram-stained sputum obtained just after the first administration of an antimicrobial agent. Case 1 was a 53-year-old man with pneumonia caused by gram-positive diplococcus, identified as S. pneumoniae, who was administered 2 g of ampicillin over a period of 1 h. Gram-stained sputum showed smaller or gram-negative pneumococci at the completion of administration of the agent, a decreased number of cocci at 1 h after administration, and almost no cocci at 12 h after the completion of administration. Case 2 was a 72-year-old woman with pneumonia caused by diplococcus, identified as S. pneumoniae, who was administered 2 g of ampicillin over a period of 1 h. Gram-stained sputum showed weakly stained, small cocci at the completion of administration of the agent and few cocci at 1 h after the completion of administration. Case 3 was a 58-year-old woman with pneumonia caused by a gram-negative diplococcus, identified as Moraxella catarrhalis, who was administered 1 g of cefotaxime over a period of 30 min. Gram-stained sputum showed few extracellular cocci and some intracellular cocci inside neutrophils 1 h after administration and no cocci 2 h after the completion of administration. These three cases showed that gram-stained sputum obtained just after and/or 1 h after administration of the first antimicrobial agent were suitable as the quickest therapeutic indicator of the effectiveness of empiric therapy, with the effectiveness of the agent being shown much earlier than with markers such as the white blood cell count and C-reactive protein level. PMID:23073648

Fujisaki, Ryuichi; Yamaoka, Toshimori; Yamamura, Michiko; Kawakami, Sayoko; Ono, Yasuo; Miyazawa, Yukihisa; Teramoto, Tamio; Nishiya, Hajime

2013-06-01

148

Characteristics of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolated from the nasopharynges of asymptomatic children and molecular analysis of S. pneumoniae and H. influenzae strain replacement in the nasopharynx.  

PubMed

Nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in 226 children in different settings (in a crèche [day care center], in an orphanage, and at home) during two seasons (winter and spring) was studied. The rates of carriage of S. pneumoniae and H. influenzae were markedly higher in the crèche and in the orphanage than in the home setting (e.g., 56.5, 63.3, and 25.9%, respectively, for S. pneumoniae in winter). Approximately 80% of the S. pneumoniae isolates identified in the crèche and in the orphanage belonged to the serotypes represented in the seven-valent pneumococcal vaccine, and 4.4% of the children were colonized by H. influenzae type b. Almost all H. influenzae isolates were fully susceptible to the antimicrobial agents tested, and only five (3.6%) produced beta-lactamase; in contrast, 100% of the M. catarrhalis isolates were beta-lactamase positive. Among S. pneumoniae isolates, 36.2% were nonsusceptible to penicillin (PNSP) and 11.8% were fully resistant to penicillin (PRP). All PNSP isolates were obtained from children at the crèche and at the orphanage but not among children brought up at home, and all PRP isolates showed a multiresistant phenotype. Colonization by PRP isolates correlated well with prior treatment with beta-lactams. For the majority of children colonized at both sampling times, strain replacement of S. pneumoniae and H. influenzae was observed; long-term colonization by a single strain was rare. PMID:15364973

Sulikowska, Agnieszka; Grzesiowski, Pawel; Sadowy, Ewa; Fiett, Janusz; Hryniewicz, Waleria

2004-09-01

149

Characterization of a Moraxella species that causes epistaxis in macaques.  

PubMed

Bacteria of the genus Moraxella have been isolated from a variety of mammalian hosts. In a prior survey of bacteria that colonize the rhesus macaque nasopharynx, performed at the Tulane National Primate Research Center, organisms of the Moraxella genus were isolated from animals with epistaxis, or "bloody nose syndrome." They were biochemically identified as Moraxella catarrhalis, and cryopreserved. Another isolate was obtained from an epistatic cynomolgus macaque at the U.S. Army Medical Research Institute of Infectious Diseases. Based on differences in colony and cell morphologies between rhesus and human M. catarrhalis isolates, we hypothesized that the nonhuman primate Moraxella might instead be a different species. Despite morphological differences, the rhesus isolates, by several biochemical tests, were indistinguishable from M. catarrhalis. Analysis of the cynomolgus isolate by Vitek 2 Compact indicated that it belonged to a Moraxella group, but could not differentiate among species. However, sequencing of the 16S ribosomal RNA gene from four representative rhesus isolates and the cynomolgus isolate showed closest homology to Moraxella lincolnii, a human respiratory tract inhabitant, with 90.16% identity. To examine rhesus macaques as potential hosts for M. catarrhalis, eight animals were inoculated with human M. catarrhalis isolates. Only one of the animals was colonized and showed disease, whereas four of four macaques became epistatic after inoculation with the rhesus Moraxella isolate. The nasopharyngeal isolates in this study appear uniquely adapted to a macaque host and, though they share many of the phenotypic characteristics of M. catarrhalis, appear to form a genotypically distinct species. PMID:20667430

Embers, Monica E; Doyle, Lara A; Whitehouse, Chris A; Selby, Edward B; Chappell, Mark; Philipp, Mario T

2011-01-27

150

Total genome polymorphism and low frequency of intra-genomic variation in the uspA1 and uspA2 genes of Moraxella catarrhalis in otitis prone and non-prone children up to 2 years of age. Consequences for vaccine design?  

PubMed

Intra-genomic variation in the uspA1 and uspA2 genes of Moraxella catarrhalis was studied using pulsed field gel electrophoresis (PFGE) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. From a set of 91 M. catarrhalis isolates, 19 pairs of PFGE identical isolates were found. Five pairs originated from otitis non-prone children, 11 pairs from otitis prone children and for 3 pairs, one of the pair originated from an otitis prone and the other from an otitis non-prone child. No particular M. catarrhalis isolate was associated with either the otitis prone or non-prone children. One of these 19 pairs of isolates was found to exhibit both uspA1 and uspA2 intra-genomic variation, whilst another pair exhibited uspA2 intra-genomic variation only. Sequence data obtained from these variants showed that PCR-RFLP pattern differences reflected actual changes in predicted amino acid composition and that minor amino acid changes in a 23 base pair "NINNIY" repeat region (a conserved UspA1 and UspA2 binding site for the neutralising antibody mAb17C7) occurred. Variation in the uspA2 5' non-coding "AGAT" repeat region was also observed. These results may have implications for future M. catarrhalis vaccines comprising UspA1 or UspA2 components. PMID:12559789

Hays, John P; van der Schee, Cindy; Loogman, Anita; Eadie, Kim; Verduin, Cees; Faden, Howard; Verbrugh, Henri; van Belkum, Alex

2003-03-01

151

Carcinoembryonic antigen (CEA)-related cell adhesion molecules are co-expressed in the human lung and their expression can be modulated in bronchial epithelial cells by non-typable Haemophilus influenzae, Moraxella catarrhalis, TLR3, and type I and II interferons  

PubMed Central

Background The carcinoembryonic antigen (CEA)-related cell adhesion molecules CEACAM1 (BGP, CD66a), CEACAM5 (CEA, CD66e) and CEACAM6 (NCA, CD66c) are expressed in human lung. They play a role in innate and adaptive immunity and are targets for various bacterial and viral adhesins. Two pathogens that colonize the normally sterile lower respiratory tract in patients with chronic obstructive pulmonary disease (COPD) are non-typable Haemophilus influenzae (NTHI) and Moraxella catarrhalis. Both pathogens bind to CEACAMs and elicit a variety of cellular reactions, including bacterial internalization, cell adhesion and apoptosis. Methods To analyze the (co-) expression of CEACAM1, CEACAM5 and CEACAM6 in different lung tissues with respect to COPD, smoking status and granulocyte infiltration, immunohistochemically stained paraffin sections of 19 donors were studied. To address short-term effects of cigarette smoke and acute inflammation, transcriptional regulation of CEACAM5, CEACAM6 and different CEACAM1 isoforms by cigarette smoke extract, interferons, Toll-like receptor agonists, and bacteria was tested in normal human bronchial epithelial (NHBE) cells by quantitative PCR. Corresponding CEACAM protein levels were determined by flow cytometry. Results Immunohistochemical analysis of lung sections showed the most frequent and intense staining for CEACAM1, CEACAM5 and CEACAM6 in bronchial and alveolar epithelium, but revealed no significant differences in connection with COPD, smoking status and granulocyte infiltration. In NHBE cells, mRNA expression of CEACAM1 isoforms CEACAM1-4L, CEACAM1-4S, CEACAM1-3L and CEACAM1-3S were up-regulated by interferons alpha, beta and gamma, as well as the TLR3 agonist polyinosinic:polycytidylic acid (poly I:C). Interferon-gamma also increased CEACAM5 expression. These results were confirmed on protein level by FACS analysis. Importantly, also NTHI and M. catarrhalis increased CEACAM1 mRNA levels. This effect was independent of the ability to bind to CEACAM1. The expression of CEACAM6 was not affected by any treatment or bacterial infection. Conclusions While we did not find a direct correlation between CEACAM1 expression and COPD, the COPD-associated bacteria NTHi and M. catarrhalis were able to increase the expression of their own receptor on host cells. Further, the data suggest a role for CEACAM1 and CEACAM5 in the phenomenon of increased host susceptibility to bacterial infection upon viral challenge in the human respiratory tract.

2013-01-01

152

Plasmid-mediated beta-lactamase in Branhamella catarrhalis.  

PubMed

The plasmid-mediated beta-lactamase in Branhamella catarrhalis (BRO-1), also occurring in Moraxella nonliquefaciens, differs from other known plasmid-mediated beta-lactamases in Gram-negative bacteria regarding substrate profile and isoelectric point. B. catarrhalis strains previously reported to produce beta-lactamases deviating from BRO-1 were tested, and the beta-lactamases did not differ significantly from BRO-1 in substrate profile, isoelectric point or relative substrate affinity index (RSAI). Further investigations of strains of various geographic origin should be undertaken. RSAI seems to be a useful tool for screening of beta-lactamases in B. catarrhalis since values for a large number of strains can easily be determined. The previously reported conjugational transfer of BRO-1 production within species B. catarrhalis and from M. nonliquefaciens to B. catarrhalis was confirmed. Four bands of extrachromosomal DNA were regularly detected by agarose gel electrophoresis in beta-lactamase-producing as well as in beta-lactamase-negative strains of B. catarrhalis and M. non-liquefaciens, provided that the excessive nuclease activity in the preparations was inhibited. PMID:3488198

Kamme, C; Eliasson, I; Knutson, B K; Vang, M

1986-01-01

153

Moraxella Catarrhalis: A Common Cause of Childhood Illnesses  

MedlinePLUS

... to Prevent SIDS Allergic Reactions Caused By Food Allergies Protective Eyewear Reduces Risk of Head, Eye and Face Injuries in Field Hockey Study Outlines Common Risky Behaviors of Children Struck by ...

154

Moraxella bovis hemolysin.  

PubMed

Moraxella bovis hemolysin was readily filterable through polycarbonate membrane filters, but not through nitrocellulose filters. The hemolysin was filterable through polycarbonate filters with pore diameters of greater than or equal to 0.015 micron (APD). Of the hemolytic activity of cell-free filtrates, 74% could be pelleted by ultracentrifugation at 100,000 X g for 2 1/2 hours. Hemolytic activity could be demonstrated in preparations of outer membrane fragments isolated from log-phase cultures. Hemolysin in M bovis broth cultures reached a maximum concentration in late logarithmic phase (4.5 hours after inoculation) and declined thereafter. Hemolysin was inactivated by heat, trypsin, formalin, and lyophilization. PMID:6497144

Ostle, A G; Rosenbusch, R F

1984-09-01

155

Wound infection caused by Branhamella catarrhalis.  

PubMed Central

Branhamella catarrhalis was isolated from sputum, tracheal secretions, and a nonhealing and infected thoracic surgical wound in a 59-year-old woman who had a history of a chronic, interstitial fibrosis and who had undergone an open lung biopsy procedure. The patient's upper respiratory tract was the likely source of the organism. To our knowledge, this is the first report of a wound infection caused by B. catarrhalis.

Gray, L D; Van Scoy, R E; Anhalt, J P; Yu, P K

1989-01-01

156

In vitro Antibiotic Sensitivity of Moraxella Species  

Microsoft Academic Search

Minimal inhibitory concentrations of 17 antibacterial agents for 34 Moraxella strains were determined using a plate dilution method. A strain of Moraxella nonliquefaciens was found which produced ?-lactamase and was resistant to ampicillin and carbenicillin but not to cephalothin. Several strains were relatively resistant to erythromycin and sulfisoxazole. Disk sensitivity tests could be used to reliably predict penicillin and erythromycin

Samuel L. Rosenthal; Lawrence F. Freundlich; Gerald L. Gilardi; Francine Y. Clodomar

1978-01-01

157

Moraxella porci sp. nov., isolated from pigs.  

PubMed

Nine Gram-negative, catalase- and oxidase-positive, coccus-shaped bacteria were isolated from pigs affected by different pathological processes. Phenotypic and genotypic methods were adopted to determine the relationships of these new isolates to recognized species of the genus Moraxella. Analysis of the 16S rRNA gene sequences demonstrated that the clinical isolates represented a new lineage within the genus Moraxella. The isolates were closely related to Moraxella cuniculi and Moraxella pluranimalium with 16S rRNA gene sequence similarities of 98.1?% and 99.1?%, respectively. The isolates displayed DNA-DNA relative binding ratios of 74?% to each other, but distinctly lower levels of DNA-DNA hybridization were observed with phylogenetically closely related moraxellae (<32?%). The new isolates could be distinguished from all other recognized species of the genus Moraxella by physiological and biochemical tests. On the basis of the phenotypic and molecular data, the nine new isolates from pigs represent a novel species within the genus Moraxella, for which the name Moraxella porci sp. nov. is proposed. The type strain is SN9-4M(T) (=CECT 7294(T)=CCUG 54912(T)). PMID:19946050

Vela, A I; Sánchez-Porro, C; Aragón, V; Olvera, A; Domínguez, L; Ventosa, A; Fernández-Garayzábal, J F

2010-10-01

158

Antimicrobial activity of innate immune molecules against Streptococcus pneumoniae, Moraxella catarrhalis and nontypeable Haemophilus influenzae  

Microsoft Academic Search

BACKGROUND: Despite its direct connection to the nasopharynx which harbors otitis media pathogens as part of its normal flora, the middle ear cavity is kept free of these bacteria by as yet unknown mechanisms. Respiratory mucosal epithelia, including those of the middle ear and eustachian tube, secrete antimicrobial effectors including lysozyme, lactoferrin and ? defensins-1 and -2. To elucidate the

Haa-Yung Lee; Ali Andalibi; Paul Webster; Sung-Kyun Moon; Karen Teufert; Sung-Ho Kang; Jian-Dong Li; Mitsuyoshi Nagura; Tomas Ganz; David J Lim

2004-01-01

159

Lipids of Branhamella catarrhalis and Neisseria gonorrhoeae.  

PubMed Central

Three strains of Branhamella catarrhalis and three strains of Neisseria gonorrhoeae were analyzed with regard to their phospholipid and neutral lipid composition. B. catarrhalis (ATCC 23246) contained 5.12 +/- 0.34% lipid, determined gravimetrically, compared to 8.56 +/- 0.15% and 9.73 +/- 0.06% for two strains of N. gonorrhoeae. Cardiolipin, phosphatidylglycerol, and phosphatidyl-ethanolamine were identified in extracts of both species. In addition, B. catarrhalis contained small amounts of phosphatidylcholine, and N. gonorrhoeae contained small amounts of lyso-phosphatidylethanolamine, which accumulated with autolysis accompanying late cell culture growth. The kinetics of change of relative amounts of phospholipids in both species were measured and found to differ substantially. Neutral lipid accounted for 30.4% of the total lipid of B. catarrhalis (ATCC 23246) and 7.6% of the total lipid of N. gonorrhoeae NYH 002. Hydrocarbons, triglycerides, free fatty acids, coenzyme Q, diglycerides, and free hydroxy fatty acids were identified in the neutral lipid fraction of both species. The three strains of N. gonorrhoeae, sensitive, intermediate, and resistant to penicillin, exhibited no significant difference in the composition or metabolism of phospholipid. Images

Beebe, J L; Wlodkowski, T J

1976-01-01

160

Branhamella catarrhalis: epidemiology, surface antigenic structure, and immune response.  

PubMed Central

Over the past decade, Branhamella catarrhalis has emerged as an important human pathogen. The bacterium is a common cause of otitis media in children and of lower respiratory tract infections in adults with chronic obstructive pulmonary disease. B. catarrhalis is exclusively a human pathogen. It colonizes the respiratory tract of a small proportion of adults and a larger proportion of children. Studies involving restriction enzyme analysis of genomic DNA show that colonization is a dynamic process, with the human host eliminating and acquiring new strains frequently. The surface of B. catarrhalis contains outer membrane proteins, lipooligosaccharide, and pili. The genes which encode several outer membrane proteins have been cloned, and some of these proteins are being studied as potential vaccine antigens. Analysis of the immune response has been limited by the lack of an adequate animal model of B. catarrhalis infection. New information regarding outer membrane structure should guide studies of the human immune response to B. catarrhalis. Immunoassays which specifically detect antibodies to determinants exposed on the bacterial surface will elucidate the most relevant immune response. The recognition of B. catarrhalis as an important human pathogen has stimulated research on the epidemiology and surface structures of the bacterium. Future studies to understand the mechanisms of infection and to elucidate the human immune response to infection hold promise of developing new methods to treat and prevent infections caused by B. catarrhalis.

Murphy, T F

1996-01-01

161

Interaction of Streptococcus pneumoniae and Moraxella catarrhalis: Investigation of the Indirect Pathogenic Role of bLactamase Producing Moraxellae by Use of a Continuous Culture Biofilm System  

Microsoft Academic Search

system, it has been shown that the pneumococcus attains high titers in excess of 1012 CFU\\/biofilm; further- more, the penicillin-sensitive pneumococcus used remained susceptible to a range of b-lactam antibiotics in these biofilms (R. K. Budhani and J. K. Struthers, J. Antimicrob. Chemother. 40:601-602, 1997). This system was used to characterize the antibiotic susceptibility of this isolate when grown with

R. K. BUDHANI; J. K. STRUTHERS

1998-01-01

162

Plasmid profiles of Moraxella bovis isolates.  

PubMed

Two-hundred isolates of Moraxella bovis were selected at random and examined for the presence of plasmid DNA by a rapid alkaline-detergent lysis method. All isolates contained from 1 to 6 plasmids, with varying agarose-gel electrophoretic migration patterns. Most (80%) isolates carried 2 to 4 plasmids, which ranged in molecular weight from 2.6 to 80 megadaltons. Seemingly, plasmid profiles can be used as a simple, reliable epizootiologic tool to establish a strain identification scheme for M bovis. PMID:3963603

McDonald, T J; Pugh, G W

1986-04-01

163

Tetrameric repeat units associated with virulence factor phase variation in Haemophilus also occur in Netsseria spp. and Moraxella catarrhalis  

Microsoft Academic Search

The tetrameric repeat units 5?-CAAT-3? and 5?-GCAA-3? are associated with phase variable expression of lipopolysaccharide biosynthetic genes in Haemophilus influenzae. Four other tetrameric repeat units have also been reported from H. influenzae strain Rd, 5?-CAAC-3?, 5?-GACA-3?, 5?-AGCT-3?, and 5?-TTTA-3?, which are also associated with putative virulence factors. Using oligonucleotide probes corresponding to five tandem copies of each of these tetramers,

Ian R. A. Peak; Michael P. Jennings; Derek W. Hood; Marina Bisercic; E. Richard Moxon

1996-01-01

164

Infections caused by Moraxella, Moraxella urethralis, Moraxella-like groups M-5 and M-6, and Kingella kingae in the United States, 1953-1980.  

PubMed

From 1953 to 1980 the Centers for Disease Control received 933 isolates of bacteria belonging to species of the genus Moraxella, Moraxella-like Moraxella urethralis, now renamed Oligella urethralis, unnamed groups M-5 and M-6, and Kingella kingae. Ordinarily sterile sites were the source of 233 isolates. Moraxella nonliquefaciens, the most common isolate (356 strains), was recovered from upper respiratory or ocular sites in 208 (58%) of the cases. Moraxella osloensis was next most common (199 strains) but was the most frequent blood isolate (44 cases). K. kingae appeared especially invasive, with 58 of 78 isolates from blood, bone, or joint. Of the K. kingae strains, 75% were recovered from children under 6 years, compared with 23% of the other strains from that age group (P less than .01). Of the 74 isolates of group M-5, 53 were from wounds caused by dog bites; no other organism in this series was recovered from such wounds. Sixteen of the 28 M. urethralis isolates were from urine. Cases occurred as single infections, with no evidence of clusters. Of patients with infection of ordinarily sterile sites, 9.3% died; only bacteremia, meningitis, and empyema caused fatalities. Most referring laboratories (98%) had not identified the organisms to species, and only 30% had identified them to correct genus. Susceptibility testing by broth dilution revealed low MICs of penicillin (mean, 0.3; 64% less than 1 micrograms/mL). Moraxella, M. urethralis, M-5, M-6, and Kingella are important but frequently misidentified pathogens for humans; penicillin appears to be the treatment of choice. PMID:2359906

Graham, D R; Band, J D; Thornsberry, C; Hollis, D G; Weaver, R E

1990-01-01

165

Metabolism of 2-hydroxyphenylglyoxylate by Moraxella sp. strain VS1  

Microsoft Academic Search

A bacterium, designated as Moraxella sp., was enriched with 2-hydroxyphenylglyoxylate (2HPGA) as sole source of carbon and energy. Identified metabolites and enzyme activities determined with whole cells and extracts indicated that 2HPGA was degraded by an inducible sequence of enzymes via salicylaldehyde, salicylate, and gentisate; only minute amounts of salicylate were converted to catechol. Further evidence was obtained that permeases

Verona Schmidt; Rolf-Michael Wittich; Peter Fortnagel

1991-01-01

166

Moraxella osloensis Gene Expression in the Slug Host Deroceras reticulatum  

Microsoft Academic Search

BACKGROUND: The bacterium Moraxella osloensis is a mutualistic symbiont of the slug-parasitic nematode Phasmarhabditis hermaphrodita. In nature, P. hermaphrodita vectors M. osloensis into the shell cavity of the slug host Deroceras reticulatum in which the bacteria multiply and kill the slug. As M. osloensis is the main killing agent, genes expressed by M. osloensis in the slug are likely to

Ruisheng An; Srinand Sreevatsan; Parwinder S Grewal

2008-01-01

167

The Moraxella adhesin UspA1 binds to its human CEACAM1 receptor by a deformable trimeric coiled-coil.  

PubMed

Moraxella catarrhalis is a ubiquitous human-specific bacterium commonly associated with upper and lower respiratory tract infections, including otitis media, sinusitis and chronic obstructive pulmonary disease. The bacterium uses an autotransporter protein UspA1 to target an important human cellular receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Using X-ray crystallography, we show that the CEACAM1 receptor-binding region of UspA1 unusually consists of an extended, rod-like left-handed trimeric coiled-coil. Mutagenesis and binding studies of UspA1 and the N-domain of CEACAM1 have been used to delineate the interacting surfaces between ligand and receptor and guide assembly of the complex. However, solution scattering, molecular modelling and electron microscopy analyses all indicate that significant bending of the UspA1 coiled-coil stalk also occurs. This explains how UspA1 can engage CEACAM1 at a site far distant from its head group, permitting closer proximity of the respective cell surfaces during infection. PMID:18497748

Conners, Rebecca; Hill, Darryl J; Borodina, Elena; Agnew, Christopher; Daniell, Sarah J; Burton, Nicholas M; Sessions, Richard B; Clarke, Anthony R; Catto, Lucy E; Lammie, Donna; Wess, Timothy; Brady, R Leo; Virji, Mumtaz

2008-06-18

168

Identification of Branhamella catarrhalis in 2.5 min with an indoxyl butyrate strip test.  

PubMed Central

Branhamella catarrhalis, an occasional cause of human respiratory infections, unlike most other members of the family Neisseriaceae, produces a butyrate esterase. This is capable of breaking the ester linkage between butyryl groups and carrier molecules. B. caviae and B. ovis, which are rarely encountered in pathological specimens, also produce butyrate esterase. This property can be used as a rapid test in the identification of B. catarrhalis. The recently reported rapid test for butyrate esterase relies on the release of methylumbelliferate, which can be detected only by using UV light after 5 min of incubation. In the rapid test described here, indoxyl is liberated from indoxyl butyrate by butyrate esterase and spontaneously forms indigo in the presence of oxygen. B. catarrhalis can be distinguished from other oxidase-positive, gram-negative cocci after 2.5 min by inoculating the organism onto a filter paper strip containing this compound.

Dealler, S F; Abbott, M; Croughan, M J; Hawkey, P M

1989-01-01

169

Effect of selected solutes on growth and recovery of a radiation-resistant Moraxella  

Microsoft Academic Search

A highly radiation-resistant Moraxella sp. from beef was more resistant to gamma radiation in frozen beef than Clostridium botulinum 33A spores. Even though the Moraxella sp. was extremely radiation-resistant, its recovery after irradiation was markedly influenced by the plating medium. Fewer colony-forming units were recovered in Tryptic Soy Agar (TSA) than in Plate Count Agar (PCA), and differences in recovery

M. A. Bruns; R. B. Maxcy

1978-01-01

170

Amperometric microbial biosensor for p-nitrophenol using Moraxella sp.-modified carbon paste electrode  

Microsoft Academic Search

An amperometric microbial biosensor for highly specific, sensitive and rapid quantitative determination of p-nitrophenol was developed. The biosensor takes advantage of the ability of Moraxella sp. to specifically degrade p-nitrophenol to hydroquinone, a more electroactive compound than p-nitrophenol. The electrochemical oxidation current of hydroquinone formed in biodegradation of p-nitrophenol was measured at Moraxella sp.-modified carbon paste electrode and correlated to

Priti Mulchandani; Carlos M. Hangarter; Yu Lei; Wilfred Chen; Ashok Mulchandani

2005-01-01

171

Branhamella catarrhalis activates human B lymphocytes following interactions with surface IgD and class I major histocompatibility complex antigens.  

PubMed

Branhamella catarrhalis initiated DNA synthesis in human blood or spleen cells enriched for B lymphocytes but did not activate T-lymphocyte-enriched fractions. Monoclonal antibodies were used to determine which B-cell surface molecules were of importance for the activation signal. The addition of monoclonal antibodies reactive with IgD, HLA class I antigens, and B2-microglobulin to B lymphocyte cultures selectively inhibited the B-lymphocyte response to B. catarrhalis. Antibody binding to IgD and class I antigens did not inhibit B-cell proliferation following stimulation with anti-IgM beads, Staphylococcus aureus, or Epstein-Barr virus. This suggests that surface IgD is of major importance for B-lymphocyte stimulation by B. catarrhalis. Since B. catarrhalis binds HLA-ABC containing liposomes it is suggested that a similar binding of B. catarrhalis to HLA-ABC on the surface of B lymphocytes serves as an accessory factor that stabilizes the binding of B. catarrhalis to surface IgD. Activation of human B lymphocytes by B. catarrhalis resulted in changes of cell surface molecules that were quantitatively and qualitatively similar to those that resulted from the activation by S. aureus. Therefore although these two bacteria appear to activate B cells in a similar manner, they induce B-cell proliferation through interactions with different cell surface structures. PMID:2449982

Forsgren, A; Penta, A; Schlossman, S F; Tedder, T F

1988-03-01

172

Characterization of an antigenically conserved heat-modifiable major outer membrane protein of Branhamella catarrhalis.  

PubMed Central

Branhamella catarrhalis is a common cause of otitis media in children and of respiratory infections in adults with chronic bronchitis. Little is known about the antigenic structure of the outer membrane proteins (OMPs). In this study, two murine monoclonal antibodies, 7D6 and 5E8, were developed and used to characterize the major heat-modifiable OMP (OMP C/D) of B. catarrhalis. Immunoblot assays indicated that OMP C/D is heat modifiable, having a molecular mass of 55 kDa at room temperature and a mass of 60 kDa when heated under reducing conditions. Expression of the epitopes is independent of growth phase and growth media. Both epitopes are present in 51 of 51 strains of B. catarrhalis tested and are highly specific for Branhamella strains, being absent from a variety of other gram-negative species. Antibody 5E8 recognizes an epitope which is expressed on the surface of the intact bacterium. We conclude that OMP C/D is a major, heat-modifiable OMP antigen that expresses at least one stable, conserved epitope on the surface of B. catarrhalis. Future studies should focus on the role of OMP C/D in pathogenesis and on its potential role as a vaccine antigen. Images

Sarwar, J; Campagnari, A A; Kirkham, C; Murphy, T F

1992-01-01

173

Moraxella Species Are Primarily Responsible for Generating Malodor in Laundry  

PubMed Central

Many people in Japan often detect an unpleasant odor generated from laundry that is hung to dry indoors or when using their already-dried laundry. Such an odor is often described as a “wet-and-dirty-dustcloth-like malodor” or an “acidic or sweaty odor.” In this study, we isolated the major microorganisms associated with such a malodor, the major component of which has been identified as 4-methyl-3-hexenoic acid (4M3H). The isolates were identified as Moraxella osloensis by morphological observation and biochemical and phylogenetic tree analyses. M. osloensis has the potential to generate 4M3H in laundry. The bacterium is known to cause opportunistic infections but has never been known to generate a malodor in clothes. We found that M. osloensis exists at a high frequency in various living environments, particularly in laundry in Japan. The bacterium showed a high tolerance to desiccation and UV light irradiation, providing one of the possible reasons why they survive in laundry during and even after drying.

Mitani, Asako; Niwano, Yu; Takeuchi, Kohei; Tanaka, Atsushi; Yamaguchi, Noriko; Kawamura, Yoshiaki; Hitomi, Jun

2012-01-01

174

Moraxella osloensis Gene Expression in the Slug Host Deroceras reticulatum  

PubMed Central

Background The bacterium Moraxella osloensis is a mutualistic symbiont of the slug-parasitic nematode Phasmarhabditis hermaphrodita. In nature, P. hermaphrodita vectors M. osloensis into the shell cavity of the slug host Deroceras reticulatum in which the bacteria multiply and kill the slug. As M. osloensis is the main killing agent, genes expressed by M. osloensis in the slug are likely to play important roles in virulence. Studies on pathogenic interactions between bacteria and lower order hosts are few, but such studies have the potential to shed light on the evolution of bacterial virulence. Therefore, we investigated such an interaction by determining gene expression of M. osloensis in its slug host D. reticulatum by selectively capturing transcribed sequences. Results Thirteen M. osloensis genes were identified to be up-regulated post infection in D. reticulatum. Compared to the in vitro expressed genes in the stationary phase, we found that genes of ubiquinone synthetase (ubiS) and acyl-coA synthetase (acs) were up-regulated in both D. reticulatum and stationary phase in vitro cultures, but the remaining 11 genes were exclusively expressed in D. reticulatum and are hence infection specific. Mutational analysis on genes of protein-disulfide isomerase (dsbC) and ubiS showed that the virulence of both mutants to slugs was markedly reduced and could be complemented. Further, compared to the growth rate of wild-type M. osloensis, the dsbC and ubiS mutants showed normal and reduced growth rate in vitro, respectively. Conclusion We conclude that 11 out of the 13 up-regulated M. osloensis genes are infection specific. Distribution of these identified genes in various bacterial pathogens indicates that the virulence genes are conserved among different pathogen-host interactions. Mutagenesis, growth rate and virulence bioassays further confirmed that ubiS and dsbC genes play important roles in M. osloensis survival and virulence, respectively in D. reticulatum.

An, Ruisheng; Sreevatsan, Srinand; Grewal, Parwinder S

2008-01-01

175

Cultural and chemical characterization of CDC groups EO-2, M-5, and M-6, Moraxella (Moraxella) species, Oligella urethralis, Acinetobacter species, and Psychrobacter immobilis.  

PubMed

We determined phenotypic characteristics, cellular fatty acid composition, and isoprenoid quinone content of representative strains of CDC groups EO-2, M-5, and M-6, Moraxella (Moraxella) species, Oligella urethralis, Acinetobacter species, and Psychrobacter immobilis. All organisms contained ubiquinone with eight isoprene units as the major isoprenolog, but distinct differences were observed in fatty acid composition. Twenty-eight of the original collection of CDC group EO-2 strains were further identified as P. immobilis, EO-2, or EO-3 by distinctive cellular fatty acid profiles, cellular morphology, and pigment production. The cellular fatty acid compositions of M-5 and M-6 were similar but were clearly different from those of other organisms. The genus Acinetobacter was differentiated from other organisms in the study by small amounts of 2-hydroxydodecanoic acid (2-OH-12:0), and P. immobilis was differentiated by small amounts of decanoic acid (10:0) and a branched-chain 17-carbon acid (i-17:0). All Moraxella species were distinguished by small amounts of decanoic acid (10:0) and the absence of i-17:0. M. bovis, M. nonliquefaciens, and some strains of M. lacunata formed a single fatty acid group, while M. osloensis, M. phenylpyruvica, M. atlantae, and other strains of M. lacunata (M. lacunata II) had species-specific fatty acid profiles. O. urethralis differed from Moraxella species by the presence of large amounts (49%) of cis-vaccenic acid (18:1 omega 7c), small amounts (1%) of 3-hydroxyhexadecanoate (3-OH-16:0), and the absence of 10:0 and 3-hydroxydodecanoate (3-OH-12:0). The combined use of chemical data and a small number of conventional tests permitted rapid identification and differentiation of these organisms from each other and from related organisms. PMID:3356788

Moss, C W; Wallace, P L; Hollis, D G; Weaver, R E

1988-03-01

176

Presumed Endocarditis Caused by BRO ?-Lactamase-Producing Moraxella lacunata in an Infant with Fallot's Tetrad  

PubMed Central

A case of presumed endocarditis caused by Moraxella lacunata in a 15-month-old male infant with Fallot's tetrad is described. This infection may have occurred as the result of transmission of this organism between the father and his son. This is the first report of BRO ?-lactamase-producing M. lacunata causing presumed endocarditis.

Nagano, Noriyuki; Sato, Junichi; Cordevant, Christophe; Nagano, Yukiko; Taguchi, Fumiaki; Inoue, Matsuhisa

2003-01-01

177

Transcriptional regulation of type 4 pilin genes and the site-specific recombinase gene, piv, in Moraxella lacunata and Moraxella bovis.  

PubMed Central

Moraxella lacunata and Moraxella bovis use type 4 pili to adhere to epithelial tissues of the cornea and conjunctiva. Primer extension analyses were used to map the transcriptional start sites for the genes encoding the major pilin subunits (tfpQ/I) and the DNA invertase (piv), which determines pilin type expression. tfpQ/I transcription starts at a sigma54-dependent promoter (tfpQ/Ip2) and, under certain growth conditions, this transcription is accompanied by weaker upstream transcription that starts at a potential sigma70-dependent promoter (tfpQ/Ip1). piv is expressed in both M. lacunata and M. bovis from a putative sigma70-dependent promoter (pivp) under all conditions assayed. Sigma54-dependent promoters require activators in order to initiate transcription; therefore, it is likely that tfpQ/Ip2 is also regulated by an activator in Moraxella. Primer extension assays with RNA isolated from Escherichia coli containing the subcloned pilin inversion region from M. lacunata showed that pivp is used for the expression of piv; however, tfpQ/Ip2 is not used for the transcription of tfpQ/I. Transcription from tfpQ/Ip2 was activated in E. coli when the sensor (PilS) and response regulator (PilR) proteins of type 4 pilin transcription in Pseudomonas aeruginosa were expressed from a plasmid. These results suggest that the expression of the type 4 pilin in M. lacunata and M. bovis is regulated not only by a site-specific DNA inversion system but also by a regulatory system which is functionally analogous to the PilS-PilR two-component system of P. aeruginosa.

Heinrich, D W; Glasgow, A C

1997-01-01

178

Purification and properties of formate dehydrogenase from Moraxella sp. strain C-1.  

PubMed Central

NAD+-dependent formate dehydrogenase was screened in various bacterial strains. Facultative methanol-utilizing bacteria isolated from soil samples, acclimated to a medium containing methanol and formate at pH 9.5, were classified as members of the genus Moraxella. From a crude extract of Moraxella sp. strain C-1, formate dehydrogenase was purified to homogeneity, as judged by disc gel electrophoresis. The enzyme has an isoelectric point of 3.9 and a molecular weight of approximately 98,000. The enzyme is composed of two identical subunits with molecular weights of about 48,000. The apparent Km values for sodium formate and NAD+ were calculated to be 13 mM and 0.068 mM, respectively. Images

Asano, Y; Sekigawa, T; Inukai, H; Nakazawa, A

1988-01-01

179

Molecular Characterization of a Secreted Enzyme with Phospholipase B Activity from Moraxella bovis  

PubMed Central

A candidate for a vaccine against infectious bovine keratoconjunctivitis (IBK) has been cloned and characterized from Moraxella bovis. The plb gene encodes a protein of 616 amino acids (molecular mass of ?65.8 kDa) that expresses phospholipase B activity. Amino acid sequence analysis revealed that PLB is a new member of the GDSL (Gly-Asp-Ser-Leu) family of lipolytic enzymes.

Farn, Jacinta L.; Strugnell, Richard A.; Hoyne, Peter A.; Michalski, Wojtek P.; Tennent, Jan M.

2001-01-01

180

Pathway for biodegradation of p-nitrophenol in a Moraxella sp  

Microsoft Academic Search

A Moraxella strain grew on p-nitrophenol with stoichiometric release of nitrite. During induction of the enzymes for growth on p-nitrophenol, traces of hydroquinone accumulated in the medium. In the presence of 2,2â²-dipyidyl, p-nitrophenol, was converted stoichiometrically to hydroquinone. Particulate enzymes catalyzed the conversion of p-nitrophenol to hydroquinone in the presence of NADPH and oxygen. Soluble enzymes catalyzed the conversion of

J. C. Spain; D. T. Gibson

1991-01-01

181

Septic Arthritis Due to Moraxella osloensis in a Rhesus Macaque (Macaca mulatta)  

PubMed Central

A 5.5-y-old Chinese-origin female rhesus macaque (Macaca mulatta) presented for bilateral hindlimb lameness. The primate had been group-reared in an SPF breeding colony and was seronegative for Macacine herpesvirus 1, SIV, simian retrovirus type D, and simian T-lymphotropic virus. The macaque's previous medical history included multiple occasions of swelling in the left tarsus, and trauma to the right arm and bilateral hands. In addition, the macaque had experienced osteomyelitis of the left distal tibia and rupture of the right cranial cruciate ligament that had been surgically repaired. Abnormal physical examination findings on presentation included a thin body condition, mild dehydration, and bilaterally swollen stifles that were warm to the touch, with the right stifle more severely affected. Mild instability in the left stifle was noted, and decreased range of motion and muscle atrophy were present bilaterally. Hematologic findings included marked neutrophilia and lymphopenia and moderate anemia. Arthrocentesis and culture of joint fluid revealed Moraxella-like organisms. Treatment with enrofloxacin was initiated empirically and subsequently switched to cephalexin, which over time alleviated the joint swelling and inflammation. Definitive diagnosis of Moraxella osloensis septic arthritis was made through isolation of the organism and sequencing of the 16S rDNA region. To our knowledge, this report is the first description of Moraxella osloensis septic arthritis in a rhesus macaque.

Wren, Melissa A; Caskey, John R; Liu, David X; Embers, Monica E

2013-01-01

182

Thermal inactivation and injury of Moraxella-Acinetobacter cells in ground beef.  

PubMed Central

The thermal inactivation and injury (sensitivity to 0.8% NaCl) of a radiation-resistant culture of Moraxella-Acinetobacter mixed in minced beef were determined. Survival curves for Moraxella-Acinetobacter cells in beef had an initial shoulder preceding a logarithmic decline when the cells were heated at 65, 70, and 75 degrees C, but not at 80 degrees C. In all cases, the experimental points not included in the shoulder were linearized by means of a least-squares straight line, and the latter was used to determine D values. Shoulder values of 12.2, 4.1, and 0.6 min at temperatures of 65, 70, and 75 degrees C were added to the respective D values of 35.4, 6.6, and 1.4 min to determine the time required to destroy one log cycle. The Z value was 7.3 degrees C. Moraxella-Acinetobacter cells in meat were more rapidly injured than inactivated, on initial exposure to heat. The number of cells injured by this initial exposure increased as the temperature was increased. At 65 degrees C the percentage of injured cells increased more rapidly with exposure time than did the inactivated cells. As the temperature was increased, the rates of inactivation and injury became more and more similar.

Firstenberg-Eden, R; Rowley, D B; Shattuck, E

1980-01-01

183

Influence of Moraxella sp. colonization on the kidney proteome of farmed gilthead sea breams (Sparus aurata, L.)  

PubMed Central

Background Currently, presence of Moraxella sp. in internal organs of fish is not considered detrimental for fish farming. However, bacterial colonization of internal organs can affect fish wellness and decrease growth rate, stress resistance, and immune response. Recently, there have been reports by farmers concerning slow growth, poor feed conversion, and low average weight increase of fish farmed in offshore floating sea cages, often associated with internal organ colonization by Moraxella sp. Therefore, presence of these opportunistic bacteria deserves further investigations for elucidating incidence and impact on fish metabolism. Results A total of 960 gilthead sea breams (Sparus aurata, L.), collected along 17 months from four offshore sea cage plants and two natural lagoons in Sardinia, were subjected to routine microbiological examination of internal organs throughout the production cycle. Thirteen subjects (1.35%) were found positive for Moraxella sp. in the kidney (7), brain (3), eye (1), spleen (1), and perivisceral fat (1). In order to investigate the influence of Moraxella sp. colonization, positive and negative kidney samples were subjected to a differential proteomics study by means of 2-D PAGE and mass spectrometry. Interestingly, Moraxella sp. infected kidneys displayed a concerted upregulation of several mitochondrial enzymes compared to negative tissues, reinforcing previous observations following lipopolysaccharide (LPS) challenge in fish. Conclusions Presence of Moraxella sp. in farmed sea bream kidney is able to induce proteome alterations similar to those described following LPS challenge in other fish species. This study revealed that Moraxella sp. might be causing metabolic alterations in fish, and provided indications on proteins that could be investigated as markers of infection by Gram-negative bacteria within farming plants.

2010-01-01

184

Draft Genome Sequence of Moraxella bovoculi Strain 237T (ATCC BAA-1259T) Isolated from a Calf with Infectious Bovine Keratoconjunctivitis  

PubMed Central

Moraxella bovoculi is a recently identified species, recovered from the bovine eye, which is under investigation as an etiological agent of infectious bovine keratoconjunctivitis. A draft genome sequence of the Moraxella bovoculi type strain 237T has been determined to identify features that may be important during host colonization.

Foecking, Mark F.; Martin, Neal T.; Mhlanga-Mutangadura, Tendai; Reilly, Thomas J.

2014-01-01

185

Iron repressible outer membrane proteins of Moraxella bovis and demonstration of siderophore-like activity.  

PubMed

Moraxella bovis (strain Epp 63), grown in RPMI 1640 medium supplemented with desferrioxamine mesylate (0.05 mg/ml) resulted in cell free culture supernatants with an increased chromeazurol-S response indicating the presence of high affinity iron binding ligand(s). Supernatants of cultures where growth occurred in tryptic soy broth, RPMI 1640, or RPMI 1640-desferrioxamine supplemented with ferrous sulfate (10 micrograms/ml) were negative on the chromeazurol-S test. Growth of M. bovis in RPMI 1640 or RPMI 1640-desferrioxamine medium induced the expression of previously unrecognized outer membrane proteins whose expression was repressed when the medium was supplemented with iron and which were not produced when growth occurred in tryptic soy broth. PMID:9054127

Fenwick, B; Rider, M; Liang, J; Brightman, A

1996-02-01

186

General approach to bacterial nutrition: growth factor requirements of Moraxella nonliquefaciens.  

PubMed Central

A general procedure was devised for the determination of growth factor requirements of heterotrophic bacteria based upon identification of individual nutrients as they are successively depleted from a limited quantity of complex medium. By using this approach, it was possible to develop a defined medium for growth of Moraxella nonliquefaciens that contained nine amino acids and three vitamins. Three of the amino acids, proline, serine, and cysteine, were required in unusually high concentrations to obtain optimal growth. Methionine had a sparing action on the requirements for serine and cysteine. Glycine could substitute for serine. Although a required nutrient, cysteine was inhibitory for growth, but this inhibitory action was antagonized by valine or leucine. The requirement for cysteine was satisfied by cystine, glutathione, or sodium sulfide. M. nonliquefaciens could not use ammonia as a nitrogen source but could use glutamate or aspartate for this purpose. With the exception of 1 auxotrophic strain, the growth factor requirements of 23 independently isolated strains of M. nonliquefaciens were essentially the same.

Juni, E; Heym, G A; Bradley, R A

1984-01-01

187

Pathway for biodegradation of p-nitrophenol in a Moraxella sp  

SciTech Connect

A Moraxella strain grew on p-nitrophenol with stoichiometric release of nitrite. During induction of the enzymes for growth on p-nitrophenol, traces of hydroquinone accumulated in the medium. In the presence of 2,2{prime}-dipyidyl, p-nitrophenol, was converted stoichiometrically to hydroquinone. Particulate enzymes catalyzed the conversion of p-nitrophenol to hydroquinone in the presence of NADPH and oxygen. Soluble enzymes catalyzed the conversion of hydroquinone to {gamma}-hydroxymuconic semialdehyde, which was identified by high-performance liquid chromatography (HPLC)-mass spectroscopy. Upon addition of catalytic amounts of NAD{sup +}, {gamma}-hydroxymuconic semialdehyde was converted to {beta}-ketoadipic acid. In the presence of pyruvate and lactic dehydrogenase, substrate amounts of NAD were required and {gamma}-hydroxymuconic semialdehyde was converted to maleylacetic acid, which was identified by HPLC-mass spectroscopy. Similar results were obtained when the reaction was carried out in the presence of potassium ferricyanide. Extracts prepared from p-nitrophenol-grown cells also contained an enzyme that catalyzed the oxidation of 1,2,4-benzenetriol to maleylacetic acid. The enzyme responsible for the oxidation of 1,2,4-benzenetriol was separated from the enzyme responsible for hydroquinone oxidation by DEAE-cellulose chromatography. The results indicate that the pathway for biodegradation of p-nitrophenol involves the initial removal of the nitro group as nitrite and formation of hydroquinone.

Spain, J.C. (Air Force Engineering and Services Center, Tyndall AFB, FL (USA)); Gibson, D.T. (Univ. of Iowa, Iowa City (USA))

1991-03-01

188

Assessment of the bioequivalence of two formulations of clarithromycin extended-release 500-mg tablets under fasting and fed conditions: A single-dose, randomized, open-label, two-period, two-way crossover study in healthy Jordanian male volunteers  

Microsoft Academic Search

Background: Clarithromycin extended-release tablets are indicated for the treatment of adults with acute maxillary sinusitis caused by Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae; acute bacterial exacerbation of chronic bronchitis due to H influenzae, Haemophilus parainfluenzae, M catarrhalis, or S pneumoniae; or community acquired pneumonia due to H influenzae, H parainfluenzae, M catarrhalis, S pneumoniae, Chlamydia pneumoniae, or Mycoplasma pneumoniae.Objective:

Bashar A. Alkhalidi; Jaafar J. Tamimi; Isam I. Salem; Husain Ibrahim; Alsayed Alarabi I. Sallam

2008-01-01

189

Effects of Moraxella (Branhamella) ovis Culture Filtrates on Bovine Erythrocytes, Peripheral Mononuclear Cells, and Corneal Epithelial Cells†  

PubMed Central

Infectious bovine keratoconjunctivitis (IBK) is a highly contagious ocular disease that affects cattle of all ages and that occurs worldwide. Piliated hemolytic Moraxella bovis is recognized as the etiologic agent of IBK. According to data from the Nebraska Veterinary Diagnostic Laboratory System, however, Moraxella (Branhamella) ovis has been isolated with increasing frequency from cattle affected with IBK. The objective of this study was, therefore, to examine M. ovis field isolates for the presence of the putative virulence factors of M. bovis. Culture filtrates from selected M. ovis field isolates demonstrated hemolytic activity on bovine erythrocytes and cytotoxic activity on bovine peripheral blood mononuclear cells and corneal epithelial cells. The hemolytic activity of the culture filtrates was attenuated after heat treatment. Polyclonal antibodies raised against the M. bovis hemolysin-cytotoxin also recognized a protein of approximately 98 kDa in a Western blot assay. These data indicate that the M. ovis field isolates examined produce one or more heat-labile exotoxins and may suggest that M. ovis plays a role in the pathogenesis of IBK.

Cerny, Henry E.; Rogers, Douglas G.; Gray, Jeffrey T.; Smith, David R.; Hinkley, Susanne

2006-01-01

190

Amino acid sequence homology between Piv, an essential protein in site-specific DNA inversion in Moraxella lacunata, and transposases of an unusual family of insertion elements.  

PubMed Central

Deletion analysis of the subcloned DNA inversion region of Moraxella lacunata indicates that Piv is the only M. lacunata-encoded factor required for site-specific inversion of the tfpQ/tfpI pilin segment. The predicted amino acid sequence of Piv shows significant homology solely with the transposases/integrases of a family of insertion sequence elements, suggesting that Piv is a novel site-specific recombinase. Images

Lenich, A G; Glasgow, A C

1994-01-01

191

Pathogenicity of Moraxella osloensis, a Bacterium Associated with the Nematode Phasmarhabditis hermaphrodita, to the Slug Deroceras reticulatum  

PubMed Central

Moraxella osloensis, a gram-negative bacterium, is associated with Phasmarhabditis hermaphrodita, a nematode parasite of slugs. This bacterium-feeding nematode has potential for the biological control of slugs, especially the grey garden slug, Deroceras reticulatum. Infective juveniles of P. hermaphrodita invade the shell cavity of the slug, develop into self-fertilizing hermaphrodites, and produce progeny, resulting in host death. However, the role of the associated bacterium in the pathogenicity of the nematode to the slug is unknown. We discovered that M. osloensis alone is pathogenic to D. reticulatum after injection into the shell cavity or hemocoel of the slug. The bacteria from 60-h cultures were more pathogenic than the bacteria from 40-h cultures, as indicated by the higher and more rapid mortality of the slugs injected with the former. Coinjection of penicillin and streptomycin with the 60-h bacterial culture reduced its pathogenicity to the slug. Further work suggested that the reduction and loss of pathogenicity of the aged infective juveniles of P. hermaphrodita to D. reticulatum result from the loss of M. osloensis from the aged nematodes. Also, axenic J1/J2 nematodes were nonpathogenic after injection into the shell cavity. Therefore, we conclude that the bacterium is the sole killing agent of D. reticulatum in the nematode-bacterium complex and that P. hermaphrodita acts only as a vector to transport the bacterium into the shell cavity of the slug. The identification of the toxic metabolites produced by M. osloensis is being pursued.

Tan, Li; Grewal, Parwinder S.

2001-01-01

192

Assessment of Bdellovibrio bacteriovorus 109J killing of Moraxella bovis in an in vitro model of infectious bovine keratoconjunctivitis.  

PubMed

The objective of this study was to determine the potential of Bdellovibrio bacteriovorus 109J as an alternative non-chemotherapeutic treatment of infectious bovine keratoconjunctivitis (IBK). To accomplish this, various parameters of B. bacteriovorus predation of Moraxella bovis were determined in vitro. Initial passage of B. bacteriovorus using M. bovis as prey required 10 d for active cultures to develop compared with 2 d for culture on normal Escherichia coli prey; however by the 5th passage, time to active predatory morphology was reduced to 2 d. This high passage B. bacteriovorus culture [1 × 10(10) plaque forming units (PFU)/mL] killed 76% of M. bovis [1 × 10(7) colony forming units (CFU)/mL] present in suspension broth in a 4 h assay. The minimal level of M. bovis supporting B. bacteriovorus predation was 1 × 10(4) CFU/mL. To assess the ability of B. bacteriovorus to kill M. bovis on an epithelial surface mimicking IBK, an in vitro assay with Madin-Darby bovine kidney (MDBK) cells inoculated with 4 × 10(7) CFU/mL M. bovis was used. Treatment with a B. bacteriovorus suspension (1.6 × 10(11) PFU/mL) decreased adherence of M. bovis to MDBK cells by 6-fold at 12 h of treatment, as well as decreased the number of unattached M. bovis cells by 1.4-fold. This study demonstrates that B. bacteriovorus has potential as an effective biological control of M. bovis at levels likely present in IBK-infected corneal epithelia and ocular secretions. PMID:22468026

Boileau, Mélanie J; Clinkenbeard, Kenneth D; Iandolo, John J

2011-10-01

193

Surface polysaccharide of Moraxella non-liquefaciens identical to Neisseria meningitidis group B capsular polysaccharide. A chemical and immunological investigation.  

PubMed

In whole cell preparations of 27 nonmucoid strains of Moraxella nonliquefaciens neuraminic acid was detected by gas chromatography (GC) in 16 (59%) of the strains. Seven neuraminic-acid-containing strains were tested for agglutination with diagnostic group-specific meningococcal antisera produced in rabbits, and all were positive with group B serum. Counter-immunoelectrophoresis of bacterial suspensions of the three strains with the strongest reaction with such anti-group B serum gave distinct precipitation lines. When tested by double immunodiffusion in agarose with monoclonal antibody to meningococcal group B polysaccharide, suspension of a strain of M nonliquefaciens gave identity reaction with a strain of Neisseria meningitidis, and reacted even more strongly than the latter. Phenol extracts of M nonliquefaciens strains generally contained higher amounts of neuraminic acid than N meningitidis group B strains. Neuraminic-acid-containing polysaccharides of M nonliquefaciens strains sedimented more slowly by ultra-centrifugation than the group-specific B polysaccharide of N meningitidis strains. They also reacted more strongly with a monoclonal anti-group B antiserum than did N meningitidis group B capsular polysaccharide in an antibody binding inhibition test (solid phase radioimmunoassay). Immunological reactivity of the polysaccharides of both species was lost if extraction was performed with unbuffered phenol at 68 degrees C, instead of with neutral phenol at 4 degrees C. The results show that several strains of M nonliquefaciens, often inhabiting the human nose, have high levels of a surface polysaccharide chemically and immunologically closely similar to N meningitidis group B capsular polysaccharide. The cross-reactivity may have immunological implications for meningococcal disease. PMID:6413906

Bøvre, K; Bryn, K; Closs, O; Hagen, N; Frøholm, L O

1983-06-01

194

CEACAM1 inhibits Toll-like receptor 2–triggered antibacterial responses of human pulmonary epithelial cells  

Microsoft Academic Search

Although Moraxella catarrhalis and Neisseria meningitidis are important human pathogens, they often colonize the human respiratory tract without causing overt clinical symptoms. Both pathogens express structurally unrelated proteins that share the ability to stimulate the adhesion molecule CEACAM1 expressed on human cells. Here we demonstrate that the interaction of CEACAM1 with ubiquitous surface protein A1 expressed on M. catarrhalis or

Solveig Zabel; Bastian Opitz; Andreas Hocke; Julia Eitel; Philippe D N'Guessan; Lothar Lucka; Kristian Riesbeck; Wolfgang Zimmermann; Janine Zweigner; Bettina Temmesfeld-Wollbrueck; Norbert Suttorp; Bernhard B Singer; Hortense Slevogt

2008-01-01

195

Antibiotic resistance patterns among respiratory pathogens at a german university children’s hospital over a period of 10 years  

Microsoft Academic Search

Growing antimicrobial resistance among Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis is raising major concern worldwide. Strains of S. pneumoniae, H. influenzae and M. catarrhalis isolated from children with respiratory tract as well as invasive infection in a South-Western region of Germany between 1993 and 2002 were tested for susceptibility to common antibiotics including penicillins, cephalosporins and macrolides. A total

Sandra J. Arri; Kirsten Fluegge; Urban Mueller; Reinhard Berner

2006-01-01

196

Differentiation of Moraxella nonliquefaciens, M. lacunata, and M. bovis by using multilocus enzyme electrophoresis and hybridization with pilin-specific DNA probes.  

PubMed Central

Genetic relationships among strains of Moraxella nonliquefaciens, M. lacunata, and M. bovis were studied by using multilocus enzyme electrophoresis and DNA-DNA hybridization. The 74 isolates analyzed for electrophoretic variation at 12 enzyme loci were assigned to 59 multilocus genotypes. The multilocus genotypes were grouped in four major clusters, one representing strains of M. nonliquefaciens, two representing strains of M. lacunata, and one comprising strains of M. bovis and the single strain of M. equi analyzed. DNA-DNA hybridization with total genomic probes also revealed four major distinctive entities that corresponded to those identified by multilocus enzyme electrophoresis. The two distinct clusters recognized among the M. lacunata strains apparently corresponded to the species previously designated M. lacunata and M. liquefaciens. Distinction of the four entities was improved by hybridization with polymerase chain reaction products of nonconserved parts of pilin genes as DNA probes. With these polymerase chain reaction probes, new isolates of M. nonliquefaciens, M. lacunata, M. liquefaciens, and M. bovis can be identified easily by hybridization.

T?njum, T; Caugant, D A; B?vre, K

1992-01-01

197

Effect of physiological age on radiation resistance of some bacteria that are highly radiation resistant. [Micrococcus radiodurans; Micrococcus sp. isolate C-3; Moraxella sp isolate 4; Escherichia coli  

SciTech Connect

Physiological age-dependent variation in radiation resistance was studied for three bacteria that are highly radiation resistant: Micrococcus radiodurans, Micrococcus sp. isolate C-3, and Moraxella sp. isolate 4. Stationary-phase cultures of M. radiodurans and isolate C-3 were much more resistant to gamma radiation than were log-phase cultures. This pattern of relative resistance was reversed for isolate 4. Resistance of isolate 4 to UV light was also greater during log phase, although heat resistance and NaCl tolerance after heat stresses were greater during stationary phase. Radiation-induced injury of isolate 4 compared with injury of Escherichia coli B suggested that the injury process, as well as the lethal process, was affected by growth phase. The hypothesis that growth rate affects radiation resistance was tested, and results were interpreted in light of the probable confounding effect of methods used to alter growth rates of bacteria. These results indicate that dose-response experiments should be designed to measure survival during the most resistant growth phase of the organism under study. The timing is particularly important when extrapolations of survival results might be made to potential irradiation processes for foods. 17 references.

Keller, L.C.; Maxcy, R.B.

1984-05-01

198

Effects of vaccination with a Moraxella bovis bacterin on the subsequent development of signs of corneal disease and infection with M bovis in calves under natural environmental conditions.  

PubMed

A vaccination study was conducted for infectious bovine keratoconjunctivitis (IBK) in 440 purebred Hereford cattle (cows and their newborn calves) of the USDA Meat Animal Research Center cattle herd at Clay Center, Ne. The cattle were allotted to 4 groups: 60 calves were vaccinated with an autogenous Moraxella bovis bacterin (group 1); 60 calves that were matched with group 1 calves were designated nonvaccinated matched controls (group 2); 99 calves were peer group nonvaccinated controls (group 3); and 219 cows, the dams of the calves, were nonvaccinated consorts (group 4). The infection rates in cattle groups 1, 2, 3, and 4 during the summer were 96.6, 98.3, 100, and 79.1%, respectively, and the disease rates were 90, 93, 85, and 20%. The infection and the disease rates were significantly (P less than 0.01) different between claves and cows. The disease rate was also significantly different between older and younger cows. A larger percentage of the affected calves and cows had mild or moderate (61%) signs of IBK rather than severe (39%) signs. The rate of body weight gain was reduced in calves with severe signs of IBK. The results seemed to indicate that little would be gained by vaccinating cattle against IBK under the conditions of study. PMID:984561

Hughes, D E; Pugh, G W; Kohlmeier, R H; Booth, G D; Knapp, B W

1976-11-01

199

Relatedness of three species of "false neisseriae," Neisseria caviae, Neisseria cuniculi, and Neisseria ovis, by DNA-DNA hybridizations and fatty acid analysis.  

PubMed

DNA-DNA hybridization was used to determine the levels of genomic relatedness of the three species of "false neisseriae," Neisseria caviae, Neisseria cuniculi, and Neisseria ovis. The reference strains of these species exhibited high levels of intraspecies relatedness (93 to 100% for N. caviae, 79 to 100% for N. cuniculi, and 68 to 100% for N. ovis) but low levels of interspecific relatedness (less than 34%) to each other and to various species belonging to the beta subclass of the Proteobacteria (Kingella kingae, Neisseria gonorrhoeae, Neisseria meningitidis, and Oligella urethralis) or to the gamma subclass (Branhamella catarrhalis, Kingella indologenes, Moraxella atlantae, Moraxella bovis, Moraxella lacunata subsp. lacunata, Moraxella lacunata subsp. liquefaciens, Moraxella nonliquefaciens, Moraxella osloensis, and Moraxella phenylpyruvica). However, the levels of DNA-DNA hybridization for the three species of "false neisseriae" were significantly higher with the species belonging to the gamma subclass (average, 13.7%) than with the species belonging to the beta subclass (average, 4.5%). These data suggest that N. caviae, N. cuniculi, and N. ovis are three separate genomic species in the gamma subclass. An ascendant hierarchical classification based only on fatty acid profiles distinguished four main classes containing (i) most of the "classical moraxellae," the "false neisseriae," and B. catarrhalis, (ii) only Acinetobacter spp., (iii) M. nonliquefaciens and "misnamed moraxellae" (M. atlantae, M. osloensis, and M. phenylpyruvica), and (iv) the "true neisseriae," the three Kingella species, and O. urethralis. Fatty acids that distinguish these four classes were identified. The fatty acid profiles of the two strains of Psychrobacter immobilis which we studied are not very similar to the profiles of the other taxa. Our results support the hypothesis that the three species of "false neisseriae," B. catarrhalis, the "classical moraxellae," and Acinetobacter spp. should be included in the same family. PMID:8494736

Véron, M; Lenvoisé-Furet, A; Coustère, C; Ged, C; Grimont, F

1993-04-01

200

Formation of amino acid (L-leucine, L-phenylalanine) derived volatile flavour compounds by Moraxella phenylpyruvica and Staphylococcus xylosus in cured meat model systems.  

PubMed

A bacterial strain isolated from Danish immersion curing brine, Moraxella phenylpyruvica 0100, and a commercial meat starter culture, Staphylococcus xylosus DD34, were tested for their ability to form characteristic volatile compounds in minimal medium with the added amino acid L-leucine or L-phenylalanine under different environmental conditions (pH 5.5 and 6.0; 0 and 210 ppm nitrate; pre-incubation with and without agitation) and compared with respect to their ability to form volatile compounds in cured meat extracts and vacuum-packed cured meat cuts. The characteristic cured meat aroma precursors/compounds 3-methylbutanal and 3-methylbutanol were found to be formed in cured meat extracts and vacuum-packed cured meat cuts inoculated with M. phenylpyruvica. These volatiles are most probably formed by metabolic conversion of the amino acid L-leucine by M. phenylpyruvica, as they were also produced in minimal media with added L-leucine inoculated with this organism. The characteristic L-phenylalanine derived compound, benzaldehyde, formed by M. phenylpyruvica in minimal medium in the presence of nitrate (210 ppm), was not produced in any noticeable amount in cured meat extracts or vacuum-packed cured meat inoculated with M. phenylpyruvica. In contrast, benzacetaldehyde, which has been described as a possible metabolic product of the microbial conversion of L-phenylalanine, was found to be a characteristic volatile compound formed in cured meat extracts and vacuum-packed cured meat inoculated with M. phenylpyruvica, indicating an alternative metabolic pathway for L-phenylalanine by this organism in a cured meat environment. Even though S. xylosus was able to form volatile compounds characteristic of cured meats (3-methylbutanal, 3-methylbutanol) in minimal media with added L-leucine, this bacterial strain seemed not to be able to produce these characteristic volatiles in the studied cured meat systems. The present data imply that M. phenylpyruvica, in particular, is a potential meat starter for ensuring superior flavour development in cured meat. PMID:9706803

Møller, J K; Hinrichsen, L L; Andersen, H J

1998-06-30

201

Nasopharyngeal carriage of potential bacterial pathogens related to day care attendance, with special reference to the molecular epidemiology of Haemophilus influenzae  

Microsoft Academic Search

Nasopharyngeal carriage of Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis was studied in 259 children attending day care centers (DCC) in Amsterdam, The Netherlands, and in 276 control children. The DCC children were sampled a second time after 4 weeks. Carriage rates for DCC children and controls were 58 and 37% for S. pneumoniae, 37 and 11% for H. influenzae,

Paul G. H. Peerbooms; Marlene N. Engelen; Dominique A. J. Stokman; Birgit H. B. van Benthem; Maria-Lucia van Weert; Sylvia M. Bruisten; Alex van Belkum; Roel A. Coutinho

2002-01-01

202

Antimicrobial Action of Nitens® Mouthwash (Cetyltrimethylammonium Naproxenate) on Multiple Isolates of Pharyngeal Microbes: A Controlled Study against Chlorhexidine, Benzydamine, Hexetidine, Amoxicillin, Amoxicillin-Clavulanate, Clarithromycin, and Cefaclor  

Microsoft Academic Search

Background: Acute oropharyngeal and respiratory tract infections are due to a wide spectrum of microorganisms. The aim of this study was to compare and evaluate the in vitro activity of four antiseptics (cetyltrimethylammonium naproxenate, chlorhexidine, benzydamine, hexetidine) to four antibiotics (amoxicillin, amoxicillin-clavulanate, clarithromycin, cefaclor) on strains of Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes and Streptococcus pneumoniae. Methods: Susceptibility tests were

A. P. Pilloni; G. Buttini; D. Giannarelli; B. Giordano; M. R. Iovene; F. Montella; R. di Salvo; R. Colantuono; G. Lalli; M. A. Tufano

2002-01-01

203

Differentiation of some species of Neisseriaceae and other bacterial groups by DNA-DNA hybridization.  

PubMed

DNA-DNA hybridization using total genomic DNA probes may represent a way of differentiating between miscellaneous bacterial species. This was studied with type and reference strains of 20 species in Moraxella, Kingella, and other selected Gram-negative groups. Both radioactive and biotin labelling were employed. Most of the species examined were easily distinguished, such as Moraxella (Branhamella) catarrhalis, M.(B.) ovis, M. atlantae, M. phenylpyruvica, M. osloensis, Neisseria elongata, N. meningitidis, Kingella kingae, K. indologenes, K. dentrificans, Oligella urethralis, Eikenella corrodens, Cardiobacterium hominis, Haemophilus aphrophilus, Actinobacillus actinomycetemcomitans, Gardnerella vaginalis, and DF-2. This reflected the extent of the genetic distances between them as a basis for identification by hybridization. There was some clustering in the Moraxella group. Especially the closely related Moraxella nonliquefaciens, M. lacunata and M. bovis showed strong hybridization affinities. This leads to potential problems in distinguishing these three species from each other by DNA-DNA hybridization with total genomic probes alone. PMID:2730785

Tønjum, T; Bukholm, G; Bøvre, K

1989-05-01

204

Correlation between Presence of Viable Bacteria and Presence of Endotoxin in Middle-Ear Effusions  

PubMed Central

The presence of endotoxin (detected by the Limulus amebocyte lysate assay) was compared to the presence of viable Haemophilus influenzae and Moraxella catarrhalis (detected by PCR) in 106 middle-ear effusions from pediatric patients with chronic otitis media. Endotoxin was found in 81 of the 106 specimens. Of these 81 specimens, 66 (81.5%) also tested positive for one or both of the gram-negative bacteria H. influenzae and M. catarrhalis. The data suggest that viable gram-negative bacteria, detectable by PCR but often undetectable by culture, may be the source of endotoxin in middle-ear effusions.

Dingman, Jeffrey R.; Rayner, Mark G.; Mishra, Suman; Zhang, Yingze; Ehrlich, Miles D.; Post, J. Christopher; Ehrlich, Garth D.

1998-01-01

205

Portable exhausters POR-004 SKID B, POR-005 SKID C, POR-006 SKID D storage plan  

SciTech Connect

This document provides a storage plan for portable exhausters POR-004 SKID B, POR-005 SKID C, AND POR-006 SKID D. The exhausters will be stored until they are needed by the TWRS (Tank Waste Remediation Systems) Saltwell Pumping Program. The storage plan provides criteria for portable exhauster storage, periodic inspections during storage, and retrieval from storage.

Nelson, O.D.

1997-09-04

206

Population Pharmacokinetics and Pharmacodynamics of Garenoxacin in Patients with Community-Acquired Respiratory Tract Infections  

Microsoft Academic Search

Garenoxacin (T-3811ME, BMS-284756) is a novel, broad-spectrum des-F(6) quinolone currently under study for the treatment of community-acquired respiratory tract infections. This analysis assessed garenoxacin population pharmacokinetics and exposure-response relationships for safety (adverse effects (AE)) and anti- microbial activity (clinical cure and bacteriologic eradication of Streptococcus pneumoniae and the grouping of Haemophilus influenzae, Haemophilus parainfluenzae, and Moraxella catarrhalis). Data were obtained

Scott Van Wart; Luann Phillips; Elizabeth A. Ludwig; Rene Russo; Diptee A. Gajjar; Akintunde Bello; Paul G. Ambrose; Christopher Costanzo; Thaddeus H. Grasela; Roger Echols; Dennis M. Grasela

2004-01-01

207

In vitro activity of ertapenem against selected respiratory pathogens  

Microsoft Academic Search

Objectives: The in vitro activity of ertapenem was evaluated in comparison to 21 selected agents against a large collection of recently isolated respiratory tract pathogens including: 180 Streptococcus pneumoniae, 100 Streptococcus pyogenes ,7 0Haemophilus influenzae ,7 0Moraxella catarrhalis, 100 methicillin-susceptible Staphylococcus aureus and 30 Klebsiella pneumoniae. Additional in vitro tests (time-kill curves with ertapenem alone and in combination with four

A. Marchese; L. Gualco; A. M. Schito; E. A. Debbia; G. C. Schito

2004-01-01

208

Multicenter Spanish study of ciprofloxacin susceptibility in gram-negative bacteria. The Spanish Study Group on Quinolone Resistance.  

PubMed

The susceptibility of 2,426 gram-negative bacteria obtained from 18 Spanish hospitals to ciprofloxacin was evaluated. Among different medical centers, susceptibility to ciprofloxacin ranged from 83 to 100% for Enterobacteriaceae, from 35 to 100% for Pseudomonas aeruginosa, from 0 to 100% for Xanthomonas maltophilia, Acinetobacter spp. and other gram-negative non-fermenting bacilli, and from 33 to 100% for Campylobacter spp. All clinical isolates of Haemophilus influenzae, Moraxella catarrhalis and Neisseria gonorrhoeae were susceptible to ciprofloxacin. PMID:7556239

García-Rodríguez, J A; Fresnadillo, M J; García, M I; García-Sánchez, E; García-Sánchez, J E; Trujillano, I

1995-05-01

209

Emergence of multidrug-resistant Streptococcus pneumoniae: report from the SENTRY Antimicrobial Surveillance Program (1999–2003)  

Microsoft Academic Search

Emerging resistance among Streptococcus pneumoniae to penicillin, erythromycin, clindamycin, tetracyclines, and trimethoprim–sulfamethoxazole continues to compromise orally administered therapy for community-acquired respiratory tract infections. Concern also exists that multidrug-resistant (MDR) S. pneumoniae and Haemophilus influenzae strains could develop fluoroquinolone resistance (FQR). S. pneumoniae (2379 strains), H. influenzae (2456), and Moraxella catarrhalis (901) studied as part of the SENTRY Antimicrobial Surveillance Program

David M. Johnson; Matthew G. Stilwell; Thomas R. Fritsche; Ronald N. Jones

2006-01-01

210

Antimicrobial resistance trends in community-acquired respiratory tract pathogens in the Western Pacific Region and South Africa: report from the SENTRY antimicrobial surveillance program, (1998–1999) including an in vitro evaluation of BMS284756  

Microsoft Academic Search

From 1998 to 1999, a large number of community-acquired respiratory tract isolates of Streptococcus pneumoniae (n=566), Haemophilus influenzae (n=513) and Moraxella catarrhalis (n=228) were collected from 15 centres in Australia, Hong Kong, Japan, China, the Philippines, Singapore, South Africa and Taiwan through the SENTRY Antimicrobial Surveillance Program. Isolates were tested against 26 antimicrobial agents using the NCCLS-recommended methods. Overall, 40%

J. M. Bell; J. D. Turnidge; R. N. Jones

2002-01-01

211

A review of the comparative in-vitro activities of 12 antimicrobial agents, with a focus on five new 'respiratory quinolones  

Microsoft Academic Search

The efficacies of many antimicrobial agents are being threatened by a global increase in the numbers of resistant bacterial pathogens—microorganisms that were once susceptible to some of these agents. In particular, antimicrobial resistance amongst strains of Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae has limited the usefulness of first-line agents in some clinical settings. Quinolones were introduced in the 1980s

Joseph M. Blondeau

1999-01-01

212

Antimicrobial susceptibility of respiratory tract pathogens in Japan during PROTEKT years 1–3 (1999–2002)  

Microsoft Academic Search

Data are presented on antimicrobial resistance among isolates of Streptococcus pneumoniae, Streptoco-ccus pyogenes, Haemophilus influenzae, and Moraxella catarrhalis collected in Japan during years 1–3 (1999–2002) of the Prospective Resistant Organism Tracking and Epidemiology for the Ketolide\\u000a Telithromycin (PROTEKT) surveillance study. In addition to the standard panel of PROTEKT antimicrobial agents, eight other\\u000a agents often used in Japan also were tested

Matsuhisa Inoue; Kenichi Kaneko; Kouji Akizawa; Shinichi Fujita; Mitsuo Kaku; Jun Igari; Keizo Yamaguchi; Shigeru Kohno; Kiyoharu Yamanaka; Yoshitsugu Iinuma; Mitsuharu Murase; Takashi Yokoyama; Seishi Asari; Yoichi Hirakata

2006-01-01

213

Clinical bacteriology and immunology in acute otitis media in children  

Microsoft Academic Search

Acute otitis media (AOM) is the most common disease seen in childhood. Streptococcus pneumoniae, non-typeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis are the most frequent pathogens of all AOM episodes. The high prevalence of drug-resistant pathogens such as penicillin-resistant\\u000a S. pneumoniae (PRSP) and betalactamase producing or nonproducing ampicillin-resistant H. influenzae (BLPAR or BLNAR) is causing serious clinical problems worldwide. PRSP

Noboru Yamanaka; Muneki Hotomi; Dewan S. Billal

2008-01-01

214

Nasal colonization by four potential respiratory bacteria in healthy children attending kindergarten or elementary school in Seoul, Korea.  

PubMed

A longitudinal analysis was carried out of the colonization by four potential respiratory pathogens - Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus - in 165 healthy children (aged 3-7 years) attending three kindergartens and 417 healthy children (aged 7-10 years) attending an elementary school in Seoul, Korea, by four consecutive examinations over 1 year. The prevalence of nasal carriers of one or more of four bacteria was found to be higher in younger children (?7 years) (mean 68.6%) than that in older children (mean 46.8%). The mean rates of nasal carriage of Strep. pneumoniae, H. influenzae, M. catarrhalis and Staph. aureus were 16.8, 18.9, 20.2 and 18.2%, respectively. Colonization by Strep. pneumoniae, H. influenzae and M. catarrhalis was higher in pre-school children (28.6, 32.4 and 35.0%, respectively) than in school children (12.2, 13.6 and 14.3%, respectively). Carriage trends differed with age, with Strep. pneumoniae, H. influenzae and M. catarrhalis colonization decreasing with age but Staph. aureus colonization increasing. Positive associations of co-occurrence between Strep. pneumoniae, H. influenzae and M. catarrhalis were evident, with a significant negative association evident between Staph. aureus and the other three bacteria. A better understanding of the colonization and interaction of potential respiratory pathogens may be important for predicting changes in bacterial ecology and for designing control strategies that target bacterial colonization in upper respiratory tract infections. PMID:22282460

Bae, Songmee; Yu, Jae-Yon; Lee, Kwangjun; Lee, Sunhwa; Park, Bohyun; Kang, Yeonho

2012-05-01

215

Pulsed-Field Gel Electrophoresis Analysis of Nasopharyngeal Flora in Children Attending a Day Care Center  

PubMed Central

To investigate how bacterial pathogens spread from child to child in a day care center, we monitored six children, two boys and four girls, born between August 1995 and November 1997, attending a day care center and analyzed nasopharyngeal samples from them using pulsed-field gel electrophoresis (PFGE). We obtained nasopharyngeal cultures from all of the affected children and almost all of the unaffected children between September 1998 and March 1999 after some children presented simultaneously with purulent rhinorrhea. Moreover, when a child was found to have acute otitis media, nasopharyngeal secretions from the child were independently cultured during treatment. During this period, 28 isolates of Moraxella catarrhalis, 13 of Streptococcus pneumoniae, and 4 of Haemophilus influenzae were recovered. PFGE gave 8 patterns for M. catarrhalis, 10 for S. pneumoniae, and 1 for H. influenzae. PFGE patterns demonstrated spread of M. catarrhalis between children. However, each occurrence of clusters of infection with M. catarrhalis lasted 2 to 6 weeks, with a change in PFGE pattern between occurrences of clusters. The M. catarrhalis strain infecting each child also changed. Similarly, the S. pneumoniae strain in each child also changed. In contrast, infection with H. influenzae persisted for about 3 months in an affected child.

Yano, Hisakazu; Suetake, Mitsuko; Kuga, Akio; Irinoda, Kazuhiko; Okamoto, Ryoichi; Kobayashi, Toshimitsu; Inoue, Matsuhisa

2000-01-01

216

Enteritis por radiación PDQ Redirect Spanish  

Cancer.gov

Enteritis por radiación PDQ Redirect Spanish El sumario de información del PDQ® Enteritis por radiación ha sido incorporado al sumario de información Complicaciones gastrointestinales. Para proseguir utilice unos de los siguientes enlaces.(The Radiation

217

Antimicrobial susceptibility profiles among common respiratory tract pathogens: a GLOBAL perspective.  

PubMed

Antimicrobial resistance by common respiratory tract pathogens remains a global concern, but surveillance programs allow us to recognize trends in susceptibility that may help guide empiric antimicrobial selection. During 2003 to 2004, the Global Landscape On the Bactericidal Activity of Levofloxacin (GLOBAL) surveillance program collected 9323 isolates of Streptococcus pneumoniae, 5828 isolates of Haemophilus influenzae, and 1878 isolates of Moraxella catarrhalis from 15 countries worldwide, and tested them for susceptibility to commonly used antimicrobial agents at a central laboratory. For S pneumoniae, penicillin (oral) susceptibility ranged from 41.5% (Asia) to 75.3% (Europe), while susceptibility to erythromycin ranged from 23.7% (Asia) to 87.0% (Central and South America). Susceptibility to levofloxacin was > or = 98.0% for each region studied, with the minimum inhibitory concentration (90%) (MIC(90)) = 1 microg/mL. Susceptibility to ciprofloxacin was > or = 81% for each region studied, with the MIC(90) = 2 microg/mL. For H influenzae, resistance to ampicillin ranged from 8.7% (South Africa) to 29.6% (Asia), while resistance to trimethoprimsulfamethoxazole ranged from 15.3% (United States) to 40.3% (Asia). Moraxella catarrhalis isolates from each region were > 95.0% susceptible to all antimicrobials tested. Susceptibility of H influenzae and M catarrhalis to levofloxacin was > 99.0% in each country. In general, S pneumoniae resistance to penicillin and macrolides remains a concern. Although the prevalence of ss-lactamase production by H influenzae and M catarrhalis can be high, these organisms continue to be susceptible to several commonly used antimicrobials. Respiratory fluoroquinolones continue to show high activity against these 3 organisms. There has been no change in the levofloxacin MIC(90) values for S pneumoniae and only rarely have resistant isolates of H influenzae and M catarrhalis been identified worldwide. PMID:18931467

Sahm, Daniel F; Brown, Nina P; Thornsberry, Clyde; Jones, Mark E

2008-09-01

218

One third of middle ear effusions from children undergoing tympanostomy tube placement had multiple bacterial pathogens  

PubMed Central

Background Because previous studies have indicated that otitis media may be a polymicrobial disease, we prospectively analyzed middle ear effusions of children undergoing tympanostomy tube placement with multiplex polymerase chain reaction for four otopathogens. Methods Middle ear effusions from 207 children undergoing routine tympanostomy tube placement were collected and were classified by the surgeon as acute otitis media (AOM) for purulent effusions and as otitis media with effusion (OME) for non-purulent effusions. DNA was isolated from these samples and analyzed with multiplex polymerase chain reaction for Haemophilus influenzae, Streptococcus pneumoniae, Alloiococcus otitidis, and Moraxella catarrhalis. Results 119 (57%) of 207 patients were PCR positive for at least one of these four organisms. 36 (30%) of the positive samples indicated the presence of more than one bacterial species. Patient samples were further separated into 2 groups based on clinical presentation at the time of surgery. Samples were categorized as acute otitis media (AOM) if pus was observed behind the tympanic membrane. If no pus was present, samples were categorized as otitis media with effusion (OME). Bacteria were identified in most of the children with AOM (87%) and half the children with OME (51%, p?Moraxella catarrhalis were more frequently identified in middle ear effusions than Streptococcus pneumoniae. Conclusions Haemophilus influenzae, Streptococcus pneumoniae, Alloiococcus otitidis, and Moraxella catarrhalis were identified in the middle ear effusions of some patients with otitis media. Overall, we found AOM is predominantly a single organism infection and most commonly from Haemophilus influenzae. In contrast, OME infections had a more equal distribution of single organisms, polymicrobial entities, and non-bacterial agents.

2012-01-01

219

The in vitro effects of faropenem on lower respiratory tract pathogens isolated in the United Kingdom.  

PubMed

Faropenem is a new oral penem with a structure different from current beta-lactams including carbapenems. The susceptibility of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis to faropenem, a macrolide, a beta-lactam, a beta-lactam/beta-lactamase inhibitor combination and two fluoroquinolones was investigated. S. pneumoniae was the most susceptible of the three species to faropenem. The MIC(90)s of faropenem against M. catarrhalis and H. influenzae were 0.5 and 1 mg/l, respectively. They were similar to amoxiclav (MIC (90)s of 0.25 and 0.5 mg/l). The quinolones showed strong activity against H. influenzae. A cluster analysis of the activities of amoxycillin and faropenem demonstrated a direct relationship between the two antimicrobial agent's activities and resistance profiles against both S. pneumoniae and H. influenzae. PMID:12791474

Walsh, F; Amyes, A K B; Amyes, S G B

2003-06-01

220

Viral-bacterial co-infection in Australian Indigenous children with acute otitis media  

Microsoft Academic Search

Background  Acute otitis media with perforation (AOMwiP) affects 40% of remote Indigenous children during the first 18 months of life.\\u000a Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are the primary bacterial pathogens of otitis media and their loads predict clinical ear state. Our hypothesis is that antecedent\\u000a respiratory viral infection increases bacterial density and progression to perforation.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  A total of 366

Michael J Binks; Allen C Cheng; Heidi Smith-Vaughan; Theo Sloots; Michael Nissen; David Whiley; Joseph McDonnell; Amanda J Leach

2011-01-01

221

Acute otitis media.  

PubMed

One in 4 children will have at least 1 episode of acute otitis media (AOM) by age 10 years. AOM results from infection of fluid that has become trapped in the middle ear. The bacteria that most often cause AOM are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Differentiating AOM from otitis media with effusion (OME) is a critical skill for physicians, as accurate diagnosis will guide appropriate treatment of these conditions. Although fluid is present in the middle ear in both conditions, the fluid is not infected in OME as is seen in AOM patients. PMID:24439877

Dickson, Gretchen

2014-03-01

222

Antibiotics GE23077, novel inhibitors of bacterial RNA polymerase. I. Taxonomy, isolation and characterization.  

PubMed

GE 23077 factors A1, A2, B1 and B2 are novel antibiotics isolated from fermentation broths of an Actinomadura sp. strain. GE23077 antibiotics are cyclic peptides, which inhibit Escherichia coli RNA polymerase at nM concentrations. Both rifampicin-sensitive and rifampicin-resistant polymerases are inhibited, whereas E. coli DNA polymerase and wheat germ RNA polymerase are substantially not affected. In spite of the potent activity on the enzyme, the antibiotics generally show poor activity against whole cell bacteria. The spectrum of activity is restricted to Moraxella catarrhalis, including clinical isolates, with partial activity against Neisseria gonorrhoeae and Mycobacterium smegmatis. PMID:15152807

Ciciliato, Ismaela; Corti, Emiliana; Sarubbi, Edoardo; Stefanelli, Stefania; Gastaldo, Luciano; Montanini, Nicoletta; Kurz, Michael; Losi, Daniele; Marinelli, Flavia; Selva, Enrico

2004-03-01

223

Massilia sp. isolated from otitis media.  

PubMed

Common bacterial pathogens of otitis media include Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, alpha-hemolytic streptococci, and Group A streptococci. We recently isolated a gram-negative, rod-shaped, non-spore-forming bacterium from a patient with otitis media following tympanocentesis. 16S rRNA gene sequence similarity studies of effusion identified this strain (CCUG 43427AT) as Massilia sp. (99.7%). Massilia spp. have been isolated from soil, air, and immunocompromised patients. However, there are no reports of their isolation from cases of otitis media. This case report highlights a rare and novel bacterial organism of otitis media. PMID:23211666

Park, Moo Kyun; Shin, Hee Bong

2013-02-01

224

Peptide deformylase inhibitors with retro-amide scaffold: synthesis and structure-activity relationships.  

PubMed

Peptide deformylase (PDF) is a metalloprotease catalyzing the removal of a formyl group from newly synthesized proteins. Thus inhibition of PDF activity is considered to be one of the most effective antibiotic strategies. Reported herein are the synthesis and structure-activity relationship studies of retro-amide inhibitors based on actinonin, a naturally occurring PDF inhibitor. Analysis of the structure-activity relationships led to the discovery of 7a, which exhibits potent enzyme inhibition and antibacterial activity against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. PMID:20615695

Lee, Seung Kyu; Choi, Kwang Hyun; Lee, Sang Jae; Suh, Se Won; Kim, B Moon; Lee, Bong Jin

2010-08-01

225

INFLUNCIA DA SATURA?ˆO POR BASES E DO F\\  

Microsoft Academic Search

1 RESUMO ñ Este trabalho teve por objetivo avaliar o desempenho de mudas da espØcie angico-branco (Anadenanthera colubrina (Vell.) Brenan), em condiÁies diferenciadas de disponibilidade de fÛsforo no solo e de saturaÁªo por bases. Os tratamentos foram representados por um fatorial de seis nÌveis de P (0, 100, 200, 300, 400 e 500 mg\\/dm 3 ) por cinco nÌveis de

Cristina de Oliveira Gomes; Haroldo Nogueira de Paiva; Lima Neves; Ricardo Silva

2004-01-01

226

TRIPANOSOMOSIS (TRANSMITIDA POR LA MOSCA TSE—TSÉ)  

Microsoft Academic Search

RESUMEN La tripanosomosis 1 transmitida por la mosca tse-tsé es una enfermedad compleja producida por varias especies de protozoos parásitos del género Trypanosoma, transmitida cíclicamente por el género Glossina (mosca tse-tsé). Esta enfermedad puede afectar a varias especies de mamíferos pero, desde el punto de vista económico, la tripanosomosis trasmitida por la mosca tse-tsé, es especialmente importante en el ganado

2004-01-01

227

Bacterial interactions in the nasopharynx - effects of host factors in children attending day-care centers.  

PubMed

The nasopharynges of preschool children are often colonized by potentially pathogenic bacteria. The interactions between these common pathogens and certain host factors were investigated in healthy preschool children 1-6 years of age. Nasopharynx samples were collected from all 63 children attending a day-care center that experienced an outbreak of penicillin-resistant Streptococcus pneumoniae. The samples were analyzed for S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Group A Streptococci. A model for the risk of carrying these bacteria was established using logistic regression. S. pneumoniae and H. influenzae antagonize each other, whereas M. catarrhalis and S. pneumoniae have a positively association. The risk of carrying M. catarrhalis decreases with age. The time spent in day care each week was not shown to influence the rate of carriage of any of these pathogens. The negative effect of H. influenzae on S. pneumoniae is discussed in relation to the carriage of penicillin-resistant S. pneumoniae, and possible mechanisms involved in this interaction are presented. PMID:22541259

Dahlblom, Victor; Söderström, Margareta

2012-04-01

228

The prevalence of middle ear pathogens in the outer ear canal and the nasopharyngeal cavity of healthy young adults.  

PubMed

Culturing middle ear fluid samples from children with chronic otitis media with effusion (OME) using standard techniques results in the isolation of bacterial species in approximately 30-50% of the cases. Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, the classic middle ear pathogens of acute otitis media, are involved but, recently, several studies suggested Alloiococcus otitidis as an additional pathogen. In the present study, we used species-specific PCRs to establish the prevalence, in both the nasopharyngeal cavity and the outer ear, of H. influenzae, M. catarrhalis, S. pneumoniae and A. otitidis. The study group consisted of 70 healthy volunteers (aged 19-22 years). The results indicate a high prevalence (>80%) of A. otitidis in the outer ear in contrast to its absence in the nasopharynx. H. influenzae was found in both the outer ear and the nasopharynx (6% and 14%, respectively), whereas S. pneumoniae and M. catarrhalis were found only in the nasopharynx (9% and 34%, respectively).A. otitidis, described as a fastidious organism, were able to be cultured using an optimized culture protocol, with prolonged incubation, which allowed the isolation of A. otitidis in five of the nine PCR-positive samples out of the total of ten samples tested. Given the absence of the outer ear inhabitant A. otitidis from the nasopharynx, its role in the aetiology of OME remains ambiguous because middle ear infecting organisms are considered to invade the middle ear from the nasopharynx through the Eustachian tube. PMID:19895585

De Baere, T; Vaneechoutte, M; Deschaght, P; Huyghe, J; Dhooge, I

2010-07-01

229

Moxifloxacin sensitivity of respiratory pathogens in the United Kingdom.  

PubMed

The in vitro activity of moxifloxacin and comparator agents against respiratory isolates from a range of geographically distinct centres around the United Kingdom was investigated in the following study. Clinical isolates of Streptococcus pneumoniae (n = 257), Haemophilus influenzae (n = 399) and Moraxella catarrhalis (n = 253) were obtained between March 1998 and April 1999 from nine centres in the United Kingdom. Sensitivity was determined by testing each isolate for its minimum inhibitory concentration (MIC) by agar dilution. Against Streptococcus pneumoniae moxifloxacin and grepafloxacin were the most active (MIC90 = 0.25 mg/l). Trovafloxacin and sparfloxacin were the next most active (MIC90 = 0.5 mg/l) followed by levofloxacin and ciprofloxacin. MIC90 values of the six fluoroquinolones versus H. influenzae ranged from <0.0039 mg/l to 0.0625 mg/l and from <0.0039 mg/l to 0.5 mg/l for M. catarrhalis. The rank order of activity of the fluoroquinolones versus H. influenzae was moxifloxacin = trovafloxacin = grepafloxacin = sparfloxacin > ciprofloxacin > levofloxacin. Against M. catarrhalis the lowest MIC90 was that of grepafloxacin at 0.0625 mg/l followed by moxifloxacin, sparfloxacin, levofloxacin and ciprofloxacin. Trovafloxacin demonstrated the highest MIC90 at 0.5 mg/l. These results demonstrate that moxifloxacin has superior in vitro activity against respiratory tract pathogens than any other comparator quinolones available for clinical use. PMID:11892894

Dorai-John, T; Thomson, C J; Amyes, S G

2002-02-01

230

Viral-bacterial co-infection in Australian Indigenous children with acute otitis media  

PubMed Central

Background Acute otitis media with perforation (AOMwiP) affects 40% of remote Indigenous children during the first 18 months of life. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are the primary bacterial pathogens of otitis media and their loads predict clinical ear state. Our hypothesis is that antecedent respiratory viral infection increases bacterial density and progression to perforation. Methods A total of 366 nasopharyngeal swabs from 114 Indigenous children were retrospectively examined. A panel of 17 respiratory viruses was screened by PCR, and densities of S. pneumoniae, H. influenzae and M. catarrhalis were estimated by quantitative real time PCR. Data are reported by clinical ear state. Results M. catarrhalis (96%), H. influenzae (91%), S. pneumoniae (89%) and respiratory viruses (59%) were common; including rhinovirus (HRV) (38%), polyomavirus (HPyV) (14%), adenovirus (HAdV) (13%), bocavirus (HBoV) (8%) and coronavirus (HCoV) (4%). Geometric mean bacterial loads were significantly higher in children with acute otitis media (AOM) compared to children without evidence of otitis media. Children infected with HAdV were 3 times more likely (p < 0.001) to have AOM with or without perforation. Conclusion This study confirms a positive association between nasopharyngeal bacterial load and clinical ear state, exacerbated by respiratory viruses, in Indigenous children. HAdV was independently associated with acute ear states.

2011-01-01

231

Consideraciones clínicas sobre la resorción radicular externa por impactación dentaria  

Microsoft Academic Search

La resorción externa por presión (RREP) consiste en una pérdida de tejido dentinario y cementario de las raíces dentarias que se origina a nivel del ligamento periodontal, ocasionada por presiones prolongadas y mantenidas sobre la raíz. Presentamos tres casos con diferente repercusión y tratamiento. Según el distinto grado de afecta­ ción se describe y clasifica el tratamiento de RREP a

Martínez Lozano MA; Forner Navarro L; Sánchez Cortés JL

232

Evaluation of mupirocin E-test for determination of isolate susceptibility: comparison with standard agar dilution techniques.  

PubMed

Mupirocin E-test strips have been evaluated for their ease of use and accuracy in determining the susceptibilities of 171 strains of Staphylococcus spp., Streptococcus spp., Haemophilus influenzae, and Moraxella catarrhalis. The susceptibility of each strain was determined on two occasions, using parallel E-test and agar dilution methodologies each time. To ensure similar precisions for statistical analyses, E-test MICs were rounded up to a standard twofold agar dilution scale. Clear, elliptical zones were obtained against Staphylococcus spp. M. catarrhalis also gave clear zones, but the scale intercept was often difficult to interpret because of the irregular shape of the inhibition zone. Poor growth sometimes resulted in less-distinct zones of inhibition against Streptococcus spp. and H. influenzae. Excellent correlation was observed between the the E-test and agar dilution against Staphylococcus spp. and H. influenzae, with > 95% of the E-test values falling within one log2 dilution of the corresponding agar MIC. The correlation was lower for Streptococcus spp. and M. catarrhalis, with 86 and 83%, respectively, of E-test results falling within one log2 dilution of the agar MIC. When E-test MICs did not agree exactly with the corresponding agar MIC against Staphylococcus spp. or Streptococcus spp., there was a tendency for the E-test to give a lower MIC. This bias has little effect upon individual MICs in staphylococci or in the generation of susceptibility interpretation errors ( < 1.5% overall), but it could reduce population geometric mean MICs by factors of 0.78 to 0.83. This effect was more marked for Streptococcus spp., reducing the population mean by a factor of 0.73 and resulting in 0.7% major and 8% very major errors. In contrast, the E-test tended to give higher MICs against M. catarrhalis, resulting in 7.3% major errors and increasing the population geometric mean MIC by a factor of 1.60. PMID:7494011

Simpson, I N; Gisby, J; Hemingway, C P; Durodie, J; Macpherson, I

1995-09-01

233

Infección por VIH y el riesgo de cáncer  

Cancer.gov

Hoja informativa que describe el mayor riesgo de ciertos tipos de cánceres que presentan las personas con infección por VIH. Dichos cánceres son el sarcoma de Kaposi, los linfomas de Hodgkin y no Hodgkin, y los cánceres de ano, de cérvix, de hígado y de pulmón. Trata también de lo que las personas con infección por VIH pueden hacer para reducir su riesgo de cáncer o para detectar temprano la enfermedad.

234

China y EE.UU.: La Competencia por Asia  

Microsoft Academic Search

El presente trabajo tendrá como objeto analizar el desenvolvimiento de la política exterior china en el ámbito asiático. Además, la nueva doctrina estratégica de Washington y su política sobre Asia y Corea Del Norte, son susceptibles de crear inconvenientes serios para los intereses estratégicos de Beijing. Se intentará dar un panorama de los cambios sufridos en las relaciones sino\\/norteamericanas por

Gustavo A. Cardozo; Coordinador Programa Asia-Pacifico

235

Diarrea intratable causada por anomalías congénitas de los enterocitos  

Microsoft Academic Search

ExtractoFundamento: La diarrea intratable de la lactancia representa un problema grave que conlleva un grado elevado de morbilidad y mortalidad. Estos casos requieren una asistencia dedicada tanto por parte de los padres como del personal médico, dado que no se dispone de remedios fáciles. La escasez de pacientes indica que para progresar en el conocimiento de estos trastornos son necesarios

Alan D. Phillips

2006-01-01

236

Penicillin failure in the treatment of streptococcal pharyngo-tonsillitis.  

PubMed

The inadequate penetration of penicillins into the tonsillar tissues and tonsillar surface fluid and microbiologic interactions between Group A beta-hemolytic streptococci (GABHS) and other pharyngo-tonsillar bacterial flora can account for their failure in eradicating GABHS pharyngo-tonsillitis (PT). These interactions include the presence of beta-lactamase producing bacteria (BLPB) that "shield" GABHS from penicillins, the absence of bacteria that interfere with the growth of GABHS, and the coaggregation between GABHS and Moraxella catarrhalis. In the treatment of acute tonsillitis, the use of cephalosporins can overcome these interactions by eradicating aerobic BLPB, while preserving the potentially interfering organisms and eliminating GABHS. In treatment of recurrent and chronic PT, the administration of clindamycin or amoxicillin-clavulanatecan eradicates both aerobic and anaerobic BLPB, as well as GABHS. PMID:23588893

Brook, Itzhak

2013-06-01

237

On the essentiality of lipopolysaccharide to Gram-negative bacteria.  

PubMed

Lipopolysaccharide is a highly acylated saccharolipid located on the outer leaflet of the outer membrane of Gram-negative bacteria. Lipopolysaccharide is critical to maintaining the barrier function preventing the passive diffusion of hydrophobic solutes such as antibiotics and detergents into the cell. Lipopolysaccharide has been considered an essential component for outer membrane biogenesis and cell viability based on pioneering studies in the model Gram-negative organisms Escherichia coli and Salmonella. With the isolation of lipopolysaccharide-null mutants in Neisseria meningitidis, Moraxella catarrhalis, and most recently in Acinetobacter baumannii, it has become increasingly apparent that lipopolysaccharide is not an essential outer membrane building block in all organisms. We suggest the accumulation of toxic intermediates, misassembly of essential outer membrane porins, and outer membrane stress response pathways that are activated by mislocalized lipopolysaccharide may collectively contribute to the observed strain-dependent essentiality of lipopolysaccharide. PMID:24148302

Zhang, Ge; Meredith, Timothy C; Kahne, Daniel

2013-12-01

238

Evidence-based guidelines for treatment of bacterial respiratory tract infections in the era of antibiotic resistance.  

PubMed

Antimicrobial resistance in bacterial respiratory tract pathogens is a rapidly evolving and increasingly disconcerting problem. Major factors that have contributed to resistance are inappropriate prescribing of antibiotics for viral infections and the use of antibiotics with poor activity. The treatment of respiratory tract infections is significantly affected by resistance in organisms such as Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Resistance to beta-lactams, sulfonamides, and macrolides continues to rise. Evidence-based guidelines, founded on clinical and bacteriological outcomes, are imperative to treat patients effectively, to limit the spread of these pathogens, and to minimize further development of resistance. Pharmacokinetic and pharmacodynamic parameters have recently been shown to correlate with clinical outcome, and offer a more rational approach to predicting antimicrobial efficacy and determining clinically relevant susceptibility breakpoints. PMID:11339025

Jacobs, M R; Weinberg, W

2001-04-01

239

Treating acute otitis media post-PCV-7: judicious antibiotic therapy.  

PubMed

Acute otitis media (AOM) is treated with antibiotics in the United States, but the changing distribution of bacterial pathogens that cause the disorder can present physicians with several challenges. Most physicians treat AOM empirically, and their treatment choice should target Streptococcus pneumonia, nontypeable Haemophilus influenzae, and Moraxella catarrhalis, as those bacteria are most often isolated in AOM. First-line treatment for new onset AOM remains amoxicillin (80-90 mg/kg/d, divided twice daily). For persistent or recurrent AOM, guidelines recommend high-dose amoxicillin-clavulanate, cefdinir, cefprozil, cefpodoxime, cefuroxime, or ceftriaxone. Improved diagnosis and optimizing the choice of therapy by considering in vitro and in vivo efficacy of the different antibiotics will improve patient outcomes. Improved patient outcomes will result in fewer AOM episodes, decreased antibiotic resistance, and reduced direct and indirect health care costs. PMID:19667702

Casey, Janet R

2005-12-01

240

In vitro activities of peptide deformylase inhibitors against gram-positive pathogens.  

PubMed

The activities of six peptide deformylase (PDF) inhibitors against 107 respiratory tract pathogens were studied and compared to those of ciprofloxacin and amoxicillin-clavulanate. Against Streptococcus pneumoniae, BB-83698 and BB-83815 were the most active PDF inhibitors (MIC at which 90% of the organisms tested were inhibited [MIC(90)], 0.25 microg/ml). Five of the agents showed similar activity against Moraxella catarrhalis (MIC(90), 0.12 microg/ml). All PDF inhibitors were less active against Haemophilus influenzae; BB-3497 was the most active agent (MIC(90), 2 microg/ml). Five agents were studied against Chlamydia spp. and showed activity similar to that of ciprofloxacin (MIC, 0.5 to 4 microg/ml). This study demonstrates that PDF inhibitors have the potential to be developed for the treatment of respiratory tract infections. PMID:11897602

Wise, R; Andrews, J M; Ashby, J

2002-04-01

241

[Microbial structure of acute bacterial conjunctivitis].  

PubMed

Microbiological investigation of 124 patients with acute conjunctivitis which were treated in one of Tbilisi policlinics in 2010-12 years, was performed; microbial structure containing 124 microbial strains of different species was detected. Namely, following species of microorganisms were isolated: S. aureus - 35 strains (28,2%), Str. pneumoniae - 10 strains (8,1%), S. epidermidis - 6 strains (4,8%), Ps. aeruginosa - 24 strains (19,4%), Moraxella catarrhalis - 21 strains (16,9%), Haemophilus influenzae biogroup aegipticus - 17 strains (13,7%), and Klebsiella pneumoniae - 11 strains (8,9%). Identification of microorganisms was performed using classic methods of microbiological explorations and test systems API (bio Meriux). Study of sensitivity/resistance to antibiotics (ciprofloxacin, levofloxacin, tobramicin, norfoloxacin, moxifloxacin) containing in eye drops, was performed by diffusion in agar. High level of resistance to this antibiotic was found. As a result it is recommended to perform microbiological investigation in each case of acute conjunctivitis, to receive rational treatment. PMID:23567301

Chikviladze, D; Nikuradze, N; Gachechiladze, Kh; Miqeladze, M; Metreveli, D

2013-03-01

242

Prediction of the Pathogens That Are the Cause of Pneumonia by the Battlefield Hypothesis  

PubMed Central

Commensal organisms are frequent causes of pneumonia. However, the detection of these organisms in the airway does not mean that they are the causative pathogens; they may exist merely as colonizers. In up to 50% cases of pneumonia, the causative pathogens remain unidentified, thereby hampering targeting therapies. In speculating on the role of a commensal organism in pneumonia, we devised the battlefield hypothesis. In the “pneumonia battlefield,” the organism-to-human cell number ratio may be an index for the pathogenic role of the organism. Using real-time PCR reactions for sputum samples, we tested whether the hypothesis predicts the results of bacteriological clinical tests for 4 representative commensal organisms: Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas spp., and Moraxella catarrhalis. The cutoff value for the organism-to-human cell number ratio, above which the pathogenic role of the organism was suspected, was set up for each organism using 224 sputum samples. The validity of the cutoff value was then tested in a prospective study that included 153 samples; the samples were classified into 3 groups, and each group contained 93%, 7%, and 0% of the samples from pneumonia, in which the pathogenic role of Streptococcus pneumoniae was suggested by the clinical tests. The results for Haemophilus influenzae, Pseudomonas spp., and Moraxella catarrhalis were 100%, 0%, and 0%, respectively. The battlefield hypothesis enabled legitimate interpretation of the PCR results and predicted pneumonia in which the pathogenic role of the organism was suggested by the clinical test. The PCR reactions based on the battlefield hypothesis may help to promote targeted therapies for pneumonia. The prospective observatory study described in the current report had been registered to the University Hospital Medical Information Network (UMIN) registry before its initiation, where the UMIN is a registry approved by the International Committee of Medical Journal Editors (ICMJE). The UMIN registry number was UMIN000001118: A prospective study for the investigation of the validity of cutoff values established for the HIRA-TAN system (April 9, 2008).

Hirama, Takashi; Yamaguchi, Takefumi; Miyazawa, Hitoshi; Tanaka, Tomoaki; Hashikita, Giichi; Kishi, Etsuko; Tachi, Yoshimi; Takahashi, Shun; Kodama, Keiji; Egashira, Hiroshi; Yokote, Akemi; Kobayashi, Kunihiko; Nagata, Makoto; Ishii, Toshiaki; Nemoto, Manabu; Tanaka, Masahiko; Fukunaga, Koichi; Morita, Satoshi; Kanazawa, Minoru; Hagiwara, Koichi

2011-01-01

243

Epidemiology of nasopharyngeal carriage of respiratory bacterial pathogens in children and adults: cross-sectional surveys in a population with high rates of pneumococcal disease  

PubMed Central

Background To determine the prevalence of carriage of respiratory bacterial pathogens, and the risk factors for and serotype distribution of pneumococcal carriage in an Australian Aboriginal population. Methods Surveys of nasopharyngeal carriage of Streptococcus pneumoniae, non-typeable Haemophilus influenzae, and Moraxella catarrhalis were conducted among adults (?16 years) and children (2 to 15 years) in four rural communities in 2002 and 2004. Infant seven-valent pneumococcal conjugate vaccine (7PCV) with booster 23-valent pneumococcal polysaccharide vaccine was introduced in 2001. Standard microbiological methods were used. Results At the time of the 2002 survey, 94% of eligible children had received catch-up pneumococcal vaccination. 324 adults (538 examinations) and 218 children (350 examinations) were enrolled. Pneumococcal carriage prevalence was 26% (95% CI, 22-30) among adults and 67% (95% CI, 62-72) among children. Carriage of non-typeable H. influenzae among adults and children was 23% (95% CI, 19-27) and 57% (95% CI, 52-63) respectively and for M. catarrhalis, 17% (95% CI, 14-21) and 74% (95% CI, 69-78) respectively. Adult pneumococcal carriage was associated with increasing age (p = 0.0005 test of trend), concurrent carriage of non-typeable H. influenzae (Odds ratio [OR] 6.74; 95% CI, 4.06-11.2) or M. catarrhalis (OR 3.27; 95% CI, 1.97-5.45), male sex (OR 2.21; 95% CI, 1.31-3.73), rhinorrhoea (OR 1.66; 95% CI, 1.05-2.64), and frequent exposure to outside fires (OR 6.89; 95% CI, 1.87-25.4). Among children, pneumococcal carriage was associated with decreasing age (p < 0.0001 test of trend), and carriage of non-typeable H. influenzae (OR 9.34; 95% CI, 4.71-18.5) or M. catarrhalis (OR 2.67; 95% CI, 1.34-5.33). Excluding an outbreak of serotype 1 in children, the percentages of serotypes included in 7, 10, and 13PCV were 23%, 23%, and 29% (adults) and 22%, 24%, and 40% (2-15 years). Dominance of serotype 16F, and persistent 19F and 6B carriage three years after initiation of 7PCV is noteworthy. Conclusions Population-based carriage of S. pneumoniae, non-typeable H. influenzae, and M. catarrhalis was high in this Australian Aboriginal population. Reducing smoke exposure may reduce pneumococcal carriage. The indirect effects of 10 or 13PCV, above those of 7PCV, among adults in this population may be limited.

2010-01-01

244

Arabidopsis protochlorophyllide oxidoreductase A (PORA) restores bulk chlorophyll synthesis and normal development to a porB porC double mutant.  

PubMed

In angiosperms the strictly light-dependent reduction of protochlorophyllide to chlorophyllide is catalyzed by NADPH:protochlorophyllide oxidoreductase (POR). The Arabidopsis thaliana genome encodes three structurally related but differentially regulated POR genes, PORA, PORB and PORC. PORA is expressed primarily early in development-during etiolation, germination and greening. In contrast, PORB and PORC are not only expressed during seedling development but also throughout the later life of the plant, during which they are responsible for bulk chlorophyll synthesis. The Arabidopsis porB-1 porC-1 mutant displays a severe xantha (highly chlorophyll-deficient) phenotype characterized by smaller prolamellar bodies in etioplasts and decreased thylakoid stacking in chloroplasts. Here we have demonstrated the ability of an ectopic PORA overexpression construct to restore prolamellar body formation in the porB-1 porC-1 double mutant background. In response to illumination, light-dependent chlorophyll production, thylakoid stacking and photomorphogenesis are also restored in PORA-overexpressing porB-1 porC-1 seedlings and adult plants. An Arabidopsis porB-1 porC-1 double mutant can therefore be functionally rescued by the addition of ectopically expressed PORA, which suffices in the absence of either PORB or PORC to direct bulk chlorophyll synthesis and normal plant development. PMID:20012672

Paddock, Troy N; Mason, Mary E; Lima, Daniel F; Armstrong, Gregory A

2010-03-01

245

Antimicrobial resistance trends among community-acquired respiratory tract pathogens in Greece, 2009-2012.  

PubMed

The aim of the present study was to determine the antimicrobial resistance trends of respiratory tract pathogens isolated from patients with community-acquired respiratory tract infections (CARTIs) in Crete, Greece, over a 4-year period (2009-2012). A total of 588 community-acquired respiratory pathogens were isolated during the study period. Streptococcus pneumoniae was the most common organism responsible for 44.4% of CARTIs, followed by Haemophilus influenzae (44.2%) and Moraxella catarrhalis (11.4%). Among S. pneumoniae, the prevalence of isolates with intermediate- and high-level resistance to penicillin was 27.2% and 12.3%, respectively. Macrolide resistance slightly decreased from 29.4% over the period 2009-2010 to 28.8% over the period 2011-2012. Multiresistance was observed among 56 (54.4%) penicillin nonsusceptible isolates. A nonsignificant increase in resistance of H. influenzae isolates was noted for ? -lactams, cotrimoxazole, and tetracycline. Among the 67 M. catarrhalis tested, 32 produced beta-lactamase and were resistant to ampicillin. Macrolide resistance decreased over the study period. All isolates were susceptible to amoxicillin + clavulanic acid, chloramphenicol, rifampicin, and the fluoroquinolones. Although a decreasing trend in the prevalence of resistance of the three most common pathogens involved in CARTIs was noted, continuous surveillance of antimicrobial susceptibility at the local and national level remains important, in order to guide appropriate empirical antimicrobial therapy. PMID:24592201

Maraki, Sofia; Papadakis, Ioannis S

2014-01-01

246

Impact of experimental human pneumococcal carriage on nasopharyngeal bacterial densities in healthy adults.  

PubMed

Colonization of the nasopharynx by Streptococcus pneumoniae is a necessary precursor to pneumococcal diseases that result in morbidity and mortality worldwide. The nasopharynx is also host to other bacterial species, including the common pathogens Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis. To better understand how these bacteria change in relation to pneumococcal colonization, we used species-specific quantitative PCR to examine bacterial densities in 52 subjects 7 days before, and 2, 7, and 14 days after controlled inoculation of healthy human adults with S. pneumoniae serotype 6B. Overall, 33 (63%) of subjects carried S. pneumoniae post-inoculation. The baseline presence and density of S. aureus, H. influenzae, and M. catarrhalis were not statistically associated with likelihood of successful pneumococcal colonization at this study's sample size, although a lower rate of pneumococcal colonization in the presence of S. aureus (7/14) was seen compared to that in the presence of H. influenzae (12/16). Among subjects colonized with pneumococci, the number also carrying either H. influenzae or S. aureus fell during the study and at 14 days post-inoculation, the proportion carrying S. aureus was significantly lower among those who were colonized with S. pneumoniae (p?=?0.008) compared to non-colonized subjects. These data on bacterial associations are the first to be reported surrounding experimental human pneumococcal colonization and show that co-colonizing effects are likely subtle rather than absolute. PMID:24915552

Shak, Joshua R; Cremers, Amelieke J H; Gritzfeld, Jenna F; de Jonge, Marien I; Hermans, Peter W M; Vidal, Jorge E; Klugman, Keith P; Gordon, Stephen B

2014-01-01

247

Nasopharyngeal carriage of potential bacterial pathogens related to day care attendance, with special reference to the molecular epidemiology of Haemophilus influenzae.  

PubMed

Nasopharyngeal carriage of Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis was studied in 259 children attending day care centers (DCC) in Amsterdam, The Netherlands, and in 276 control children. The DCC children were sampled a second time after 4 weeks. Carriage rates for DCC children and controls were 58 and 37% for S. pneumoniae, 37 and 11% for H. influenzae, and 80 and 48% for M. catarrhalis, respectively. No increased antibiotic resistance rates were found in strains isolated from DCC children. All H. influenzae isolates were typed by random amplified polymorphic DNA (RAPD) analysis. Evidence for frequent transmission of H. influenzae strains within DCC was found. In the control group only two isolates (4%) displayed identical RAPD types versus 38% of strains from DCC children. Colonization with H. influenzae appeared to be short-lived in these children; more than half of the children harboring H. influenzae in the first sample were negative in the second sample, whereas most children still positive in the second sample had a different genotype than in the first sample. Of the newly acquired strains in the second sample, 40% were identical to a strain that had been found in a child in the same DCC in the first sample. DCC are to be considered epidemiological niches with a high potential for the spread of pathogenic microorganisms. PMID:12149338

Peerbooms, Paul G H; Engelen, Marlene N; Stokman, Dominique A J; van Benthem, Birgit H B; van Weert, Maria-Lucia; Bruisten, Sylvia M; van Belkum, Alex; Coutinho, Roel A

2002-08-01

248

Risk factors for carriage of AOM pathogens during the first 3 years of life in children with early onset of acute otitis media.  

PubMed

Abstract Conclusion: Risk factors associated with increased carriage rates are the same in children with recurrent acute otitis media (rAOM) as in healthy children. These are also known to be risk factors for the development of AOM itself. Objectives: The aim of this study was to describe risk factors for nasopharyngeal carriage in a cohort of young children at high risk of developing rAOM. Methods: Children with an onset of AOM before 6 months of age, indicating an 80% risk of developing rAOM, were enrolled in a vaccination trial on heptavalent PCV. These children were monitored for 3 years during healthy and AOM periods with nasopharyngeal cultures, physical examinations, and questionnaires. Results: A total of 109 children were included at a mean age of 5 months; 105 were followed for 3 years, 89 (82%) of whom developed rAOM. Risk factors associated with increased carriage of all major AOM pathogens were age <2 years, concurrent AOM, and fulfilment of rAOM criteria. Having siblings in day care was associated with increased carriage of Streptococcus pneumoniae and Haemophilus influenzae, recent antibiotic treatment was associated with H. influenzae and Moraxella catarrhalis carriage, and winter season was associated with M. catarrhalis carriage alone. PMID:24834935

Gisselsson-Solén, Marie; Henriksson, Gunnel; Hermansson, Ann; Melhus, Asa

2014-07-01

249

Antimicrobial Resistance Trends among Community-Acquired Respiratory Tract Pathogens in Greece, 2009-2012  

PubMed Central

The aim of the present study was to determine the antimicrobial resistance trends of respiratory tract pathogens isolated from patients with community-acquired respiratory tract infections (CARTIs) in Crete, Greece, over a 4-year period (2009–2012). A total of 588 community-acquired respiratory pathogens were isolated during the study period. Streptococcus pneumoniae was the most common organism responsible for 44.4% of CARTIs, followed by Haemophilus influenzae (44.2%) and Moraxella catarrhalis (11.4%). Among S. pneumoniae, the prevalence of isolates with intermediate- and high-level resistance to penicillin was 27.2% and 12.3%, respectively. Macrolide resistance slightly decreased from 29.4% over the period 2009-2010 to 28.8% over the period 2011-2012. Multiresistance was observed among 56 (54.4%) penicillin nonsusceptible isolates. A nonsignificant increase in resistance of H. influenzae isolates was noted for ?-lactams, cotrimoxazole, and tetracycline. Among the 67 M. catarrhalis tested, 32 produced beta-lactamase and were resistant to ampicillin. Macrolide resistance decreased over the study period. All isolates were susceptible to amoxicillin + clavulanic acid, chloramphenicol, rifampicin, and the fluoroquinolones. Although a decreasing trend in the prevalence of resistance of the three most common pathogens involved in CARTIs was noted, continuous surveillance of antimicrobial susceptibility at the local and national level remains important, in order to guide appropriate empirical antimicrobial therapy.

Maraki, Sofia; Papadakis, Ioannis S.

2014-01-01

250

2D-QSAR in hydroxamic acid derivatives as peptide deformylase inhibitors and antibacterial agents.  

PubMed

Peptide deformylase catalyzes the removal of N-formyl group from the N-formylmethionine of ribosome synthesized polypeptide in eubacteria. Quantitative structure-activity relationship (QSAR) studies have been carried out in a series of beta-sulfonyl and beta-sulfinyl hydroxamic acid derivatives for their PDF enzyme inhibitory and antibacterial activities against Escherichia coli DC2 and Moraxella catarrhalis RA21 which demonstrate that the PDF inhibitory activity in cell free and whole cell system increases with increase in molar refractivity and hydrophobicity. The comparison of the QSARs between the cell free and whole cell system indicate that the active binding sites in PDF isolated from E. coli and in M. catarrhalis RA21 are similar and the whole cell antibacterial activity is mainly due to the inhibition of PDF. Apart from this the QSARs on some matrixmetelloproteins (COL-1, COL-3, MAT and HME) and natural endopeptidase (NEP) indicate the possibilities of introducing selectivity in these hydroxamic acid derivatives for their PDF inhibitory activity. PMID:12413827

Gupta, Manish K; Mishra, Pradeep; Prathipati, Philip; Saxena, Anil K

2002-12-01

251

Impact of Experimental Human Pneumococcal Carriage on Nasopharyngeal Bacterial Densities in Healthy Adults  

PubMed Central

Colonization of the nasopharynx by Streptococcus pneumoniae is a necessary precursor to pneumococcal diseases that result in morbidity and mortality worldwide. The nasopharynx is also host to other bacterial species, including the common pathogens Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis. To better understand how these bacteria change in relation to pneumococcal colonization, we used species-specific quantitative PCR to examine bacterial densities in 52 subjects 7 days before, and 2, 7, and 14 days after controlled inoculation of healthy human adults with S. pneumoniae serotype 6B. Overall, 33 (63%) of subjects carried S. pneumoniae post-inoculation. The baseline presence and density of S. aureus, H. influenzae, and M. catarrhalis were not statistically associated with likelihood of successful pneumococcal colonization at this study’s sample size, although a lower rate of pneumococcal colonization in the presence of S. aureus (7/14) was seen compared to that in the presence of H. influenzae (12/16). Among subjects colonized with pneumococci, the number also carrying either H. influenzae or S. aureus fell during the study and at 14 days post-inoculation, the proportion carrying S. aureus was significantly lower among those who were colonized with S. pneumoniae (p?=?0.008) compared to non-colonized subjects. These data on bacterial associations are the first to be reported surrounding experimental human pneumococcal colonization and show that co-colonizing effects are likely subtle rather than absolute.

Shak, Joshua R.; Cremers, Amelieke J. H.; Gritzfeld, Jenna F.; de Jonge, Marien I.; Hermans, Peter W. M.; Vidal, Jorge E.; Klugman, Keith P.; Gordon, Stephen B.

2014-01-01

252

Upper respiratory tract microbial communities, acute otitis media pathogens, and antibiotic use in healthy and sick children.  

PubMed

The composition of the upper respiratory tract microbial community may influence the risk for colonization by the acute otitis media (AOM) pathogens Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. We used culture-independent methods to describe upper respiratory tract microbial communities in healthy children and children with upper respiratory tract infection with and without concurrent AOM. Nasal swabs and data were collected in a cross-sectional study of 240 children between 6 months and 3 years of age. Swabs were cultured for S. pneumoniae, and real-time PCR was used to identify S. pneumoniae, H. influenzae, and M. catarrhalis. The V1-V2 16S rRNA gene regions were sequenced using 454 pyrosequencing. Microbial communities were described using a taxon-based approach. Colonization by S. pneumoniae, H. influenzae, and M. catarrhalis was associated with lower levels of diversity in upper respiratory tract flora. We identified commensal taxa that were negatively associated with colonization by each AOM bacterial pathogen and with AOM. The balance of these relationships differed according to the colonizing AOM pathogen and history of antibiotic use. Children with antibiotic use in the past 6 months and a greater abundance of taxa, including Lactococcus and Propionibacterium, were less likely to have AOM than healthy children (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.25 to 0.85). Children with no antibiotic use in the past 6 months, a low abundance of Streptococcus and Haemophilus, and a high abundance of Corynebacterium and Dolosigranulum were less likely to have AOM (OR, 0.51; 95% CI, 0.31 to 0.83). An increased understanding of polymicrobial interactions will facilitate the development of effective AOM prevention strategies. PMID:22752171

Pettigrew, Melinda M; Laufer, Alison S; Gent, Janneane F; Kong, Yong; Fennie, Kristopher P; Metlay, Joshua P

2012-09-01

253

Postantibiotic and post-beta-lactamase inhibitor effects of amoxicillin plus clavulanate.  

PubMed

The postantibiotic effect (PAE) of amoxicillin-clavulanate was studied for strains of Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, and Escherichia coli. A PAE of approximately 2 h was seen for beta-lactamase-positive and -negative strains of S. aureus following 2 h of exposure to twice the MIC and did not increase at 16 times the MIC. The PAE observed with H. influenzae was clearly related to the growth rate of the organism. A PAE of 0.8 h was found for amoxicillin (four times the MIC) against a beta-lactamase-negative strain of H. influenzae (generation time, 26.3 min) and a PAE of 1.74 h was found for amoxicillin-clavulanate (twice the MIC) against a beta-lactamase-positive strain (generation time, 32.2 min). When the beta-lactamase-positive strain was growing more slowly (generation time, 120 min), the PAE of amoxicillin-clavulanate increased to > 3.32 h. The PAE of amoxicillin-clavulanate at 2/1 micrograms/ml on a beta-lactamase-producing strain of M. catarrhalis was > 2.9 h, and, as expected, the PAEs of twice the MIC on K. pneumoniae and E. coli were generally short (< 1 h). The post-beta-lactamase inhibitor effect (PLIE), determined after removal of only clavulanate, was also examined for beta-lactamase-positive strains. This was more prolonged (approximately 3 to 4 h) than the corresponding PAE for S. aureus, H. influenzae, and M. catarrhalis. The PLIE was related to the amount of beta-lactamase produced and required the presence of amoxicillin in the initial exposure period. These data may have implications for reducing the dosage of amoxicillin-clavulanate. PMID:9124843

Thorburn, C E; Molesworth, S J; Sutherland, R; Rittenhouse, S

1996-12-01

254

Tracking resistance among bacterial respiratory tract pathogens: summary of findings of the TRUST Surveillance Initiative, 2001-2005.  

PubMed

Antimicrobial resistance observed among common respiratory tract pathogens--Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis--may complicate empiric therapeutic selection to treat community-acquired respiratory tract infections. The Tracking Resistance in the United States Today (TRUST) study determined the in vitro activities of frequently prescribed antimicrobial agents against isolates collected from all 50 states from 2001 to 2005. For S pneumoniae (N = 27,781), susceptibility of selected agents in ascending order were penicillin (oral) (65.4%), trimethoprim-sulfamethoxazole (TMP-SMX) (69.5%), erythromycin (72.0%), cefuroxime (oral) (75.9%), tetracycline (85.3%), amoxicillinclavulanate (92.6%), ceftriaxone (nonmeningitis) (96.6%), and levofloxacin (99.0%). Susceptibility to levofloxacin, which was used as a representative of the respiratory fluoroquinolones, was near 99% from 2001 to 2005, and the minimum inhibitory concentration (90%) (MIC(90)) remained unchanged at 1 microg/mL. Levofloxacin and the other respiratory fluoroquinolones remained highly effective against penicillin-resistant S pneumoniae(PRSP) (98%-99% susceptible). However, susceptibility of PRSP to amoxicillin-clavulanate decreased from 62%S in 2003 to 48%S in 2005. Haemophilus influenzae susceptibility to ampicillin averaged near 70%, and near 75% to TMP-SMX. Susceptibility rates to levofloxacin and the other respiratory fluoroquinolones for H influenzae and M catarrhalis remained at or near 100%. Although resistance rates among S pneumoniae have stabilized for penicillin (oral) at elevated levels and increased for macrolides, susceptibility to the respiratory fluoroquinolones has consistently remained high, as they have for H influenzae and M catarrhalis. PMID:18931466

Sahm, Daniel F; Brown, Nina P; Draghi, Deborah C; Evangelista, Alan T; Yee, Y Cheung; Thornsberry, Clyde

2008-09-01

255

Bacterial and viral interactions within the nasopharynx contribute to the risk of acute otitis media  

PubMed Central

Summary Objectives To understand relationships between microbes in pathogenesis of acute otitis media during respiratory tract infections, we compared nasopharyngeal bacteria and respiratory viruses in symptomatic children with and without AOM. Methods We enrolled children (6–35 months) with acute symptoms suggestive of AOM and analyzed their nasopharyngeal samples for bacteria by culture and for 15 respiratory viruses by PCR. Non-AOM group had no abnormal otoscopic signs or only middle ear effusion, while AOM group showed middle ear effusion and acute inflammatory signs in pneumatic otoscopy along with acute symptoms. Results Of 505 children, the non-AOM group included 187 and the AOM group 318. One or more bacterial AOM pathogen (Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis) was detected in 78% and 96% of the non-AOM and AOM group, respectively (P < .001). Colonization with S. pneumoniae and H. influenzae, each alone, increased risk of AOM (odds ratio (OR) 2.92; 95% confidence interval (CI), .91–9.38, and 5.13; 1.36–19.50, respectively) and co-colonization with M. catarrhalis further increased risk (OR 4.36; 1.46–12.97, and 9.00; 2.05–39.49, respectively). Respiratory viruses were detected in 90% and 87% of the non-AOM and AOM group, respectively. RSV was significantly associated with risk of AOM without colonization by bacterial AOM pathogens (OR 6.50; 1.21–34.85). Conclusions Co-colonization by M. catarrhalis seems to increase risk of AOM and RSV may contribute to AOM pathogenesis even without nasopharyngeal bacterial colonization.

Ruohola, Aino; Pettigrew, Melinda M.; Lindholm, Laura; Jalava, Jari; Raisanen, Kati S.; Vainionpaa, Raija; Waris, Matti; Tahtinen, Paula A.; Laine, Miia K.; Lahti, Elina; Ruuskanen, Olli; Huovinen, Pentti

2013-01-01

256

El Instituto Nacional del Cáncer publica nuevo atlas de mortalidad por cáncer  

Cancer.gov

El Instituto Nacional del Cáncer (NCI, por sus siglas en inglés) ha publicado un nuevo atlas, el Atlas de Mortalidad por Cáncer en los Estados Unidos, 1950-94, que muestra los patrones geográficos de las tasas de mortalidad por cáncer durante más de cuatro décadas, en más de 3.000 condados a lo largo del país.

257

Compton imaging with the PorGamRays spectrometer  

NASA Astrophysics Data System (ADS)

The PorGamRays project aims to develop a portable gamma-ray detection system with both spectroscopic and imaging capabilities. The system is designed around a stack of thin Cadmium Zinc Telluride (CZT) detectors. The imaging capability utilises the Compton camera principle. Each detector is segmented into 100 pixels which are read out through custom designed Application Specific Integrated Circuits (ASICs). This device has potential applications in the security, decommissioning and medical fields. This work focuses on the near-field imaging performance of a lab-based demonstrator consisting of two pixelated CZT detectors, each of which is bonded to a NUCAM II ASIC. Measurements have been made with point 133Ba and 57Co sources located ˜35 mm from the surface of the scattering detector. Position resolution of ˜20 mm FWHM in the x and y planes is demonstrated.

Judson, D. S.; Boston, A. J.; Coleman-Smith, P. J.; Cullen, D. M.; Hardie, A.; Harkness, L. J.; Jones, L. L.; Jones, M.; Lazarus, I.; Nolan, P. J.; Pucknell, V.; Rigby, S. V.; Seller, P.; Scraggs, D. P.; Simpson, J.; Slee, M.; Sweeney, A.; PorGamRays Collaboration

258

Suppression of cytochrome P450 reductase (POR) expression in hepatoma cells replicates the hepatic lipidosis observed in hepatic POR-null mice.  

PubMed

Cytochrome P450 reductase (POR) is a microsomal electron transport protein essential to cytochrome P450-mediated drug metabolism and sterol and bile acid synthesis. The conditional deletion of hepatic POR gene expression in mice results in a marked decrease in plasma cholesterol levels counterbalanced by the accumulation of triglycerides in lipid droplets in hepatocytes. To evaluate the role of cholesterol and bile acid synthesis in this hepatic lipidosis, as well as the possible role of lipid transport from peripheral tissues, we developed a stable, small interfering RNA (siRNA)-mediated cell culture model for the suppression of POR. POR mRNA and protein expression were decreased by greater than 50% in McArdle-RH7777 rat hepatoma cells 10 days after transfection with a POR-siRNA expression plasmid, and POR expression was nearly completely extinguished by day 20. Immunofluorescent analysis revealed a marked accumulation of lipid droplets in cells by day 15, accompanied by a nearly 2-fold increase in cellular triglyceride content, replicating the lipidosis seen in hepatic POR-null mouse liver. In contrast, suppression of CYP51A1 (lanosterol demethylase) did not result in lipid accumulation, indicating that loss of cholesterol synthesis is not the basis for this lipidosis. Indeed, addition of cholesterol to the medium appeared to augment the lipidosis in POR-suppressed cells, whereas removal of lipids from the medium reversed the lipidosis. Oxysterols did not accumulate in POR-suppressed cells, discounting a role for liver X receptor in stimulating triglyceride synthesis, but addition of chenodeoxycholate significantly repressed lipid accumulation, suggesting that the absence of bile acids and loss of farnesoid X receptor stimulation lead to excessive triglyceride synthesis. PMID:21368239

Porter, Todd D; Banerjee, Subhashis; Stolarczyk, Elzbieta I; Zou, Ling

2011-06-01

259

Acceptance test report for portable exhauster POR-008/Skid F  

SciTech Connect

Portable Exhauster POR-008 was procured via HNF-0490, Specification for a Portable Exhausted System for Waste Tank Ventilation. Prior to taking ownership, acceptance testing was performed at the vendors. However at the conclusion of testing a number of issues remained that required resolution before the exhausters could be used by Project W-320. The purpose of acceptance testing documented by this report was to demonstrate compliance of the exhausters with the performance criteria established within HNF-O49O, Rev. 1 following a repair and upgrade effort at Hanford. In addition, data obtained during this testing is required for the resolution of outstanding Non-conformance Reports (NCR), and finally, to demonstrate the functionality of the associated software for the pressure control and high vacuum exhauster operating modes provided for by W-320. Additional testing not required by the ATP was also performed to assist in the disposition and close out of receiving inspection report and for application design information (system curve). Results of this testing are also captured within this document.

Kriskovich, J.R.

1998-07-24

260

Cirurgia Endoscópica Nasossinusal e da Base do Crânio Guiada por Computador  

Microsoft Academic Search

Introdução: Apesar de nas últimas décadas, as cirurgias dos seios paranasais e base de crânio terem apresentado grande progresso, principalmente com o advento dos novos instrumentais, visualização endoscópica e estudos por imagem, ainda apresentam complicações de graus variáveis. A cirurgia guiada por computador (CGC), tecnologia introduzida há poucos anos, foi idealizada para auxiliar o cirurgião na localização precisa de estruturas

Aldo C. Stamm; Shirley Pignatari; Bruno B. Sebusiani; Marcos C. Galati; Sérgio Mitsuda; Rainer G. Haetinger

2002-01-01

261

Estudio Hidrológico del río Arlanzón a su paso por el Término Municipal de Burgos  

Microsoft Academic Search

Para la ordenación del territorio en el Término Municipal de Burgos se necesita conocer el riesgo de inundación por las aguas de los ríos Arlanzón, Vena, Cardeñadijo y Ubierna. Por ello, se ha realizado un estudio hidrológico de la cuenca del Arlanzón partiendo de los datos de precipitaciones, cartografía referente a usos del suelo, edafología, geología y topografía, fotografías aéreas

Iñigo OLEAGORDIA MONTAÑA; Rebeca RODRÍGUEZ GARCÍA; Joaquín NAVARRO HEVIA; CASTILLO NOVO

262

Colocación de marcapasos diafragmático por toracotomía mínima para tratamiento de hipoincoercible  

Microsoft Academic Search

RESUMEN Presentamos un caso de hipo incoercible de cuatro años de duración y con clínica de pérdida de peso y fatiga. Refractario al tratamiento médico. Se le implantó un marcapasos diafragmático por vía intratorácica. Este aparato controla los movimientos del diafragma por estimulación eléctrica del nervio frénico. Se consiguió con ello disminuir la intensidad de los episodios de hipo. Este

JUAN JOSÉ FIBLA; GUILLERMO GÓMEZ; CÉSAR FARINA; GASPAR ESTRADA; CARLOS LEÓN

263

Gliding motility and Por secretion system genes are widespread among members of the phylum bacteroidetes.  

PubMed

The phylum Bacteroidetes is large and diverse, with rapid gliding motility and the ability to digest macromolecules associated with many genera and species. Recently, a novel protein secretion system, the Por secretion system (PorSS), was identified in two members of the phylum, the gliding bacterium Flavobacterium johnsoniae and the nonmotile oral pathogen Porphyromonas gingivalis. The components of the PorSS are not similar in sequence to those of other well-studied bacterial secretion systems. The F. johnsoniae PorSS genes are a subset of the gliding motility genes, suggesting a role for the secretion system in motility. The F. johnsoniae PorSS is needed for assembly of the gliding motility apparatus and for secretion of a chitinase, and the P. gingivalis PorSS is involved in secretion of gingipain protease virulence factors. Comparative analysis of 37 genomes of members of the phylum Bacteroidetes revealed the widespread occurrence of gliding motility genes and PorSS genes. Genes associated with other bacterial protein secretion systems were less common. The results suggest that gliding motility is more common than previously reported. Microscopic observations confirmed that organisms previously described as nonmotile, including Croceibacter atlanticus, "Gramella forsetii," Paludibacter propionicigenes, Riemerella anatipestifer, and Robiginitalea biformata, exhibit gliding motility. Three genes (gldA, gldF, and gldG) that encode an apparent ATP-binding cassette transporter required for F. johnsoniae gliding were absent from two related gliding bacteria, suggesting that the transporter may not be central to gliding motility. PMID:23123910

McBride, Mark J; Zhu, Yongtao

2013-01-01

264

An investigation of exploitation versus exploration in GBEA optimization of PORS 15 and 16 Problems  

SciTech Connect

It was hypothesized that the variations in time to solution are driven by the competing mechanisms of exploration and exploitation.This thesis explores this hypothesis by examining two contrasting problems that embody the hypothesized tradeoff between exploration and exploitation. Plus one recall store (PORS) is an optimization problem based on the idea of a simple calculator with four buttons: plus, one, store, and recall. Integer addition and store are classified as operations, and one and memory recall are classified as terminals. The goal is to arrange a fixed number of keystrokes in a way that maximizes the numerical result. PORS 15 (15 keystrokes) represents the subset of difficult PORS problems and PORS 16 (16 keystrokes) represents the subset of PORS problems that are easiest to optimize. The goal of this work is to examine the tradeoff between exploitation and exploration in graph based evolutionary algorithm (GBEA) optimization. To do this, computational experiments are used to examine how solutions evolve in PORS 15 and 16 problems when solved using GBEAs. The experiment is comprised of three components; the graphs and the population, the evolutionary algorithm rule set, and the example problems. The complete, hypercube, and cycle graphs were used for this experiment. A fixed population size was used.

Koch, Kaelynn

2012-05-08

265

Bacterium-Generated Nitric Oxide Hijacks Host Tumor Necrosis Factor Alpha Signaling and Modulates the Host Cell Cycle In Vitro  

PubMed Central

In mammalian cells, nitric oxide (NO·) is an important signal molecule with concentration-dependent and often controversial functions of promoting cell survival and inducing cell death. An inducible nitric oxide synthase (iNOS) in various mammalian cells produces higher levels of NO· from l-arginine upon infections to eliminate pathogens. In this study, we reveal novel pathogenic roles of NO· generated by bacteria in bacterium-host cell cocultures using Moraxella catarrhalis, a respiratory tract disease-causing bacterium, as a biological producer of NO·. We recently demonstrated that M. catarrhalis cells that express the nitrite reductase (AniA protein) can produce NO· by reducing nitrite. Our study suggests that, in the presence of pathophysiological levels of nitrite, this opportunistic pathogen hijacks host cell signaling and modulates host gene expression through its ability to produce NO· from nitrite. Bacterium-generated NO· significantly increases the secretion of tumor necrosis factor alpha (TNF-?) and modulates the expression of apoptotic proteins, therefore triggering host cell programmed death partially through TNF-? signaling. Furthermore, our study reveals that bacterium-generated NO· stalls host cell division and directly results in the death of dividing cells by reducing the levels of an essential regulator of cell division. This study provides unique insight into why NO· may exert more severe cytotoxic effects on fast growing cells, providing an important molecular basis for NO·-mediated pathogenesis in infections and possible therapeutic applications of NO·-releasing molecules in tumorigenesis. This study strongly suggests that bacterium-generated NO· can play important pathogenic roles during infections.

Mocca, Brian

2012-01-01

266

Antibiotic therapy in acute exacerbations of chronic bronchitis.  

PubMed

Chronic obstructive pulmonary disease (COPD) comprises a spectrum of conditions including chronic bronchitis, emphysema, asthma, and bronchiectasis. It has a prevalence in the United States of 5.1% to 5.4% in the middle-aged to elderly population, with a lower rate in nonsmoking individuals. Moreover, COPD is complicated by frequent and recurring acute exacerbations of chronic bronchitis (AECB). Overall, COPD represents the fourth leading cause of mortality in the United States and is the second leading cause of work disability. This condition is also associated with high morbidity and health care expenditures. Despite the controversy over the need to prescribe antibiotics for patients with AECB, high-risk patients have been identified who will benefit from this therapy.These include, patients with a history of repeated infections (>4 per year), comorbid illnesses (such as diabetes, asthma, coronary heart disease), or marked airway obstruction. Furthermore, a bacterial cause is shown in approximately 50% of AECB episodes, and primarily includes Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Additionally, resistance among community-acquired respiratory pathogens in the United States has risen dramatically, with beta-lactamase production evident in 40% of H. influenzae and greater than 95% of M. catarrhalis isolates, and with approximately 10% of pneumococci highly resistant to penicillin and simultaneously resistant to macrolide antibiotics. The criteria used to make choices for antibiotic use in patients with AECB should include knowledge of the frequencies of pathogen resistance and patients' clinical characteristics. An effective antibiotic, however, must be able to rapidly resolve the acute infection with the least patient morbidity and need for hospitalization. Although there remains controversy as to when to initiate antibiotic therapy in patients with AECB, several guidelines have been published. PMID:11052424

Adams, S G; Anzueto, A

2000-09-01

267

Clinical studies of garenoxacin.  

PubMed

Garenoxacin mesylate hydrate (GRN) is a novel oral des-fluoro(6) quinolone with potent antimicrobial activity against common respiratory pathogens, including resistant strains. It has favourable pharmacokinetic profiles for maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC), with good penetration into sputum and otorhinolaryngological tissues. In clinical studies, the efficacy of GRN ranged from 92% to 96% in patients with bacterial pneumonia, mycoplasma pneumonia, chlamydial pneumonia and acute bronchitis. Efficacy was 85% in acute infectious exacerbations of chronic respiratory disease and ranged from 81% to 95% in otorhinolaryngological infections. Bacterial eradication was 90.9% for Staphylococcus aureus, 99.2% for Streptococcus pneumoniae, 98.2% for Haemophilus influenzae, 96.6% for Moraxella catarrhalis, 100% for penicillin-resistant S. pneumoniae, 100% for beta-lactamase-negative ampicillin-resistant H. influenzae and beta-lactamase-positive H. influenzae, and 96.2% for beta-lactamase-positive M. catarrhalis. Garenoxacin concentrations in plasma and tissues using GRN 400mg once a day were higher than the MIC90 (minimum inhibitory concentration for 90% of the organisms) of major causative pathogens. The trough concentration (Cmin) in plasma was 1.92 microg/mL, a level that was higher than the mutant prevention concentration, suggesting that GRN is unlikely to induce the selection of resistant strains during treatment. In clinical studies, GRN did not produce class adverse effects of fluoroquinolones such as QTc prolongation, blood glucose abnormality or severe liver damage. No serious adverse events were observed during the trials. The results indicate that GRN is very effective in treating patients with upper and lower respiratory tract infections. PMID:18790608

Takagi, Hiroyasu; Tanaka, Kiyoshi; Tsuda, Hisatsugu; Kobayashi, Hiroyuki

2008-12-01

268

In young children, persistent wheezing is associated with bronchial bacterial infection: a retrospective analysis  

PubMed Central

Background Young children with persistent wheezing pose a diagnostic and therapeutical challenge to the pediatrician. We aimed to evaluate bacterial bronchial infection as a possible reason for non response to conventional asthma therapy, and to identify and characterise the predominant pathogens involved. Methods We retrospectively analysed microbiological and cytological findings in a selected population of young wheezers with symptoms unresponsive to inhaled corticosteroid (ICS) therapy, who underwent flexible bronchoscopy with bronchoalveolar lavage (BAL). Procedural measures were taken to limit contamination risk and quantitative bacterial culture of BAL fluid (significance cut-off???104 colony-forming units/ml) was used. Modern microbiological methods were used for detection of a wide panel of pathogens and for characterisation of the bacterial isolates. Results 33 children aged between 4 and 38?months, without structural anomalies of the conductive airways were evaluated. Significant bacterial BAL cultures were found in 48,5?% of patients. Haemophilus influenzae was isolated in 30,3?%, Streptococcus pneumoniae in 12,1?% and Moraxella catarrhalis in 12,1?%. All H. influenzae isolates were non-encapsulated strains and definitely distinguished from non-haemolytic H. haemolyticus. Respiratory viruses were detected in 21,9?% of cases with mixed bacterial-viral infection in 12,1?%. Cytology revealed a marked neutrophilic inflammation. Conclusions Bacterial infection of the bronchial tree is common in persistent preschool wheezers and provides a possible explanation for non response to ICS therapy. Non-typeable H. influenzae seems to be the predominant pathogen involved, followed by S. pneumoniae and M. catarrhalis.

2012-01-01

269

Use of an Oligonucleotide Array for Laboratory Diagnosis of Bacteria Responsible for Acute Upper Respiratory Infections  

PubMed Central

We developed a diagnostic array of oligonucleotide probes targeting species-specific variable regions of the genes encoding topoisomerases GyrB and ParE of respiratory bacterial pathogens. Suitable broad-range primer sequences were designed based on alignment of gyrB/parE sequences from nine different bacterial species. These species included Corynebacterium diphtheriae, Fusobacterium necrophorum, Haemophilus influenzae, Legionella pneumophila, Moraxella catarrhalis, Mycoplasma pneumoniae, Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes. Specific probe sequences were selected by comparative analysis against the European Bioinformatics Database, as well as gyrB/parE sequences generated for this study. To verify specificity, at least six initial oligonucleotide probe sequences per bacterial species were tested by hybridization on a solid glass support using culture collection strains as templates. Finally, three oligonucleotide probes per bacterial species were utilized to examine 65 middle ear fluid and 29 throat swab samples. The sensitivities of the developed assay compared to classic culture from middle ear fluid samples for H. influenzae, M. catarrhalis, and S. pneumoniae were 96 (93 for culture), 73 (93 for culture), and 100% (78% for culture), respectively. No cross-reactivity with bacterial species belonging to the normal oral flora was observed when the 29 throat swab samples were studied. The sensitivity of the assay to detect S. pyogenes from these samples was 93% (80% for culture). These results provide a proof of concept for the diagnostic use of microarray technology based on broad-range topoisomerase gene amplification, followed by hybridization and specific detection of bacterial species.

Roth, Stina B.; Jalava, Jari; Ruuskanen, Olli; Ruohola, Aino; Nikkari, Simo

2004-01-01

270

Nasopharyngeal Bacterial Colonization and Gene Polymorphisms of Mannose-Binding Lectin and Toll-Like Receptors 2 and 4 in Infants  

PubMed Central

Background Human nasopharynx is often colonized by potentially pathogenic bacteria. Gene polymorphisms in mannose-binding lectin (MBL), toll-like receptor (TLR) 2 and TLR4 have been reported. The present study aimed to investigate possible association between nasopharyngeal bacterial colonization and gene polymorphisms of MBL, TLR2 and TLR4 in healthy infants. Methodology/Principal Findings From August 2008 to June 2010, 489 nasopharyngeal swabs and 412 blood samples were taken from 3-month-old healthy Finnish infants. Semi-quantitative culture was performed and pyrosequencing was used for detection of polymorphisms in MBL structural gene at codons 52, 54, and 57, TLR2 Arg753Gln and TLR4 Asp299Gly. Fifty-nine percent of subjects were culture positive for at least one of the four species: 11% for Streptococcus pneumoniae, 23% for Moraxella catarrhalis, 1% for Haemophilus influenzae and 25% for Staphylococcus aureus. Thirty-two percent of subjects had variant types in MBL, 5% had polymorphism of TLR2, and 18% had polymorphism of TLR4. Colonization rates of S. pneumoniae and S. aureus were significantly higher in infants with variant types of MBL than those with wild type (p?=?.011 and p?=?.024). Colonization rates of S. aureus and M. catarrhalis were significantly higher in infants with polymorphisms of TLR2 and of TLR4 than those without (p?=?.027 and p?=?.002). Conclusions Our study suggests that there is an association between nasopharyngeal bacterial colonization and genetic variation of MBL, TLR2 and TLR4 in young infants. This finding supports a role for these genetic variations in susceptibility of children to respiratory infections.

Vuononvirta, Juho; Toivonen, Laura; Grondahl-Yli-Hannuksela, Kirsi; Barkoff, Alex-Mikael; Lindholm, Laura; Mertsola, Jussi; Peltola, Ville; He, Qiushui

2011-01-01

271

PorA Represents the Major Cell Wall Channel of the Gram-Positive Bacterium Corynebacterium glutamicum  

PubMed Central

The cell wall of the gram-positive bacterium Corynebacterium glutamicum contains a channel (porin) for the passage of hydrophilic solutes. The channel-forming polypeptide PorA is a 45-amino-acid acidic polypeptide with an excess of four negatively charged amino acids, which is encoded by the 138-bp gene porA. porA was deleted from the chromosome of C.glutamicum wild-type strain ATCC 13032 to obtain mutant ATCC 13032?porA. Southern blot analysis demonstrated that porA was deleted. Lipid bilayer experiments revealed that PorA was not present in the cell wall of the mutant strain. Searches within the known chromosome of C. glutamicum by using National Center for Biotechnology Information BLAST and reverse transcription-PCR showed that no other PorA-like protein is encoded on the chromosome or is expressed in the deletion strain. The porA deletion strain exhibited slower growth and longer growth times than the C. glutamicum wild-type strain. Experiments with different antibiotics revealed that the susceptibility of the mutant strain was much lower than that of the wild-type C. glutamicum strain. The results presented here suggest that PorA represents a major hydrophilic pathway through the cell wall and that C. glutamicum contains cell wall channels which are not related to PorA.

Costa-Riu, Noelia; Burkovski, Andreas; Kramer, Reinhard; Benz, Roland

2003-01-01

272

Preparation and Characterization of Neisseria meningitidis Mutants Deficient in Production of the Human Lactoferrin-Binding Proteins LbpA and LbpB  

PubMed Central

Pathogenic members of the family Neisseriaceae produce specific receptors facilitating iron acquisition from transferrin (Tf) and lactoferrin (Lf) of their mammalian host. Tf receptors are composed of two outer membrane proteins, Tf-binding proteins A and B (TbpA and TbpB; formerly designated Tbp1 and Tbp2, respectively). Although only a single Lf-binding protein, LbpA (formerly designated Lbp1), had previously been recognized, we recently identified additional bacterial Lf-binding proteins in the human pathogens Neisseria meningitidis and Moraxella catarrhalis and the bovine pathogen Moraxella bovis by a modified affinity isolation technique (R. A. Bonnah, R.-H. Yu, and A. B. Schryvers, Microb. Pathog. 19:285–297, 1995). In this report, we characterize an open reading frame (ORF) located immediately upstream of the N. meningitidis B16B6 lbpA gene. Amino acid sequence comparisons of various TbpBs with the product of the translated DNA sequence from the upstream ORF suggests that the region encodes the Lf-binding protein B homolog (LbpB). The LbpB from strain B16B6 has two large stretches of negatively charged amino acids that are not present in the various transferrin receptor homologs (TbpBs). Expression of the recombinant LbpB protein as a fusion with maltose binding protein demonstrated functional Lf-binding activity. Studies with N. meningitidis isogenic mutants in which the lbpA gene and the ORF immediately upstream of lbpA (putative lbpB gene) were insertionally inactivated demonstrated that LbpA, but not LbpB, is essential for iron acquisition from Lf in vitro.

Bonnah, Robert A.; Schryvers, Anthony B.

1998-01-01

273

Aspectos macroeconómicos de las utilidades por compraventa de divisas de la cuenta especial de cambios  

Microsoft Academic Search

Este trabajo persigue dos objetivos. En primer lugar, se discute el origen de las utilidades por compraventa de divisas (UCVD) de la Cuenta Especial de Cambios (CEC) y la naturaleza de su trabajo al gobierno. En segundo término, se analizan los efectos macroeconómicos de la utilización de los recursos de las UCVD para la financiación del déficit del gobierno, haciendo

Armando Montenegro

1983-01-01

274

Primer reporte de enfermedad sistémica por arañazo de gato (Bartonella henselae) en el Perú  

Microsoft Academic Search

RESUMEN Introducción: la enfermedad por arañazo de gato(EAG) en la mayoría de las veces es descrita en su forma típica, las formas sistémicas son raras y de escaso reporte. La EAG puede tener una gran variedad de presentaciones, siendo algunas de ellas poco frecuentes. Es la primera vez que se reporta esta forma de presentación en el Perú. Caso clínico:

Pablo Manuel Polanco Aguilar; Mario Cornejo Giraldo; Elert Zapata Aguilar; Víctor Hugo; Calderón Arenas; Patricia Márquez Díaz; Ciro Maguiña Vargas

2008-01-01

275

Characterization of Plasmid pOR1 from Ornithobacterium rhinotracheale and Construction of a Shuttle Plasmid  

Microsoft Academic Search

The bacterium Ornithobacterium rhinotracheale has been recognized as an emerging pathogen in poultry since about 10 years ago. Knowledge of this bacterium and its mechanisms of virulence is still very limited. Here we report the development of a transformation system that enables genetic modification of O. rhinotracheale. The system is based on a cryptic plasmid, pOR1, that was derived from

Ruud Jansen; Niwat Chansiripornchai; Wim Gaastra; Jos P. M. van Putten

2004-01-01

276

Revisión de mejores prácticas en modelos de negocio utilizados por entidades microfinancieras  

Microsoft Academic Search

Este documento presenta tres modelos de negocio utilizados por entidades microfinancieras y que a nuestro entender son mejores prácticas en sus respectivos ámbitos de actuación. En primer lugar, el caso analizado de Banco Compartamos refleja un proceso de transformación exitosa de una organización no gubernamental sin ánimo de lucro en entidad bancaria. Adicionalmente, el éxito de su salida al mercado

Francesc Prior; Javier Santoma

2008-01-01

277

Mortalidade precoce por doenças do coração no brasil. Comparação com outros países  

Microsoft Academic Search

Objetivo - Comparar a mortalidade por doenças do coração e pela doença coronária (DC) nas faixas etárias dos 45 aos 64 anos, no período 1984-87, em capitais bra- sileiras com outros países. Métodos - Foram utilizadas as estatísticas oficiais de mortalidade de 8 capitais com boa qualidade de informa- ção: Belém, Recife, Salvador, Belo Horizonte, Rio de Ja- neiro, São

Paulo Andrade Lotufo

1998-01-01

278

Consecuencias de la restricción de peso impuesta por el deporte en la infancia  

Microsoft Academic Search

ExtractoActualmente, los competidores jóvenes emprenden programas de entrenamiento que se basan en un nivel elevado de actividad física desde una temprana edad. Este entrenamiento intensivo (volumen e intensidad) aumenta el gasto de energía, que tiene que ser compensado por una mayor ingesta nutricional. Los bailarines de ballet, los patinadores artísticos, los gimnastas o los gimnastas rítmicos comienzan a entrenar a

Nathalie Boisseau

2006-01-01

279

Otimização por Enxame de Partículas aplicado à formação e atuação de grupos robóticos  

Microsoft Academic Search

Resumo Neste artigo, descreve-se o modelo, a implementação e a avaliação da eficiência de Algoritmos de Otimização por Enxame de Partículas aplicados à formação e atuação de grupos robóticos. A atuação do grupo robótico é realizada sobre um desastre ambiental do tipo incêndio florestal. São avaliados diversos parâmetros que influenciam o comportamento da otimização, como inércia, confiança, tipos de modelos

Gustavo Pessin; Fernando Osório

2009-01-01

280

Associations between Pathogens in the Upper Respiratory Tract of Young Children: Interplay between Viruses and Bacteria  

PubMed Central

Background High rates of potentially pathogenic bacteria and respiratory viruses can be detected in the upper respiratory tract of healthy children. Investigating presence of and associations between these pathogens in healthy individuals is still a rather unexplored field of research, but may have implications for interpreting findings during disease. Methodology/Principal Findings We selected 986 nasopharyngeal samples from 433 6- to 24-month-old healthy children that had participated in a randomized controlled trial. We determined the presence of 20 common respiratory viruses using real-time PCR. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus were identified by conventional culture methods. Information on risk factors was obtained by questionnaires. We performed multivariate logistic regression analyses followed by partial correlation analysis to identify the overall pattern of associations. S. pneumoniae colonization was positively associated with the presence of H. influenzae (adjusted odds ratio 1.60, 95% confidence interval 1.18–2.16), M. catarrhalis (1.78, 1.29–2.47), human rhinoviruses (1.63, 1.19–2.22) and enteroviruses (1.97, 1.26–3.10), and negatively associated with S. aureus presence (0.59, 0.35–0.98). H. influenzae was positively associated with human rhinoviruses (1.63, 1.22–2.18) and respiratory syncytial viruses (2.78, 1.06–7.28). M. catarrhalis colonization was positively associated with coronaviruses (1.99, 1.01–3.93) and adenoviruses (3.69, 1.29–10.56), and negatively with S. aureus carriage (0.42, 0.25–0.69). We observed a strong positive association between S. aureus and influenza viruses (4.87, 1.59–14.89). In addition, human rhinoviruses and enteroviruses were positively correlated (2.40, 1.66–3.47), as were enteroviruses and human bocavirus, WU polyomavirus, parainfluenza viruses, and human parechovirus. A negative association was observed between human rhinoviruses and coronaviruses. Conclusions/Significance Our data revealed high viral and bacterial prevalence rates and distinct bacterial-bacterial, viral-bacterial and viral-viral associations in healthy children, hinting towards the complexity and potential dynamics of microbial communities in the upper respiratory tract. This warrants careful consideration when associating microbial presence with specific respiratory diseases.

van den Bergh, Menno R.; Biesbroek, Giske; Rossen, John W. A.; de Steenhuijsen Piters, Wouter A. A.; Bosch, Astrid A. T. M.; van Gils, Elske J. M.; Wang, Xinhui; Boonacker, Chantal W. B.; Veenhoven, Reinier H.; Bruin, Jacob P.

2012-01-01

281

[Antibacterial activity for clinical isolates from pediatric patients of clavulanic acid/amoxicillin (1: 14) -outcomes of special drug use investigation on antibacterial activity (annual changes)].  

PubMed

As a special drug use investigation, we monitored and assessed trends in antibacterial activity of clavulanic acid/amoxicillin (1:14) (hereafter, "CVA/AMPC (1:14)") and other antimicrobial agents for clinical isolates from pediatric patients with otitis media or respiratory, skin, and urinary tract infections. Against Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis isolated and identified from otorrhea, epipharynx and rhinorrhea of pediatric patients with otitis media, the MIC90s of CVA/AMPC (1:14) in five years between 2006-2010 were 1 microg/mL for S. pneumoniae and 8 microg/mL for H. influenzae and 0.25-0.5microg/mL for M catarrhalis. The changes of MIC90s of CVA/AMPC (1:14) for penicillin-resistant S. pneumoniae (PRSP) and beta-lactamase non-producing H. influenzae were two times, and no decrease in drug susceptibility was found in the period of the present investigation. In addition, the MIC changes of other antimicrobial agents for these three organisms were approximately two to four times as well. Against organisms isolated and identified from pus, sputum, pharynx, skin and urine of pediatric patients with respiratory, skin, and urinary tract infections, the MIC90s of CVA/AMPC (1:14) in four years between 2008-2011 were 1 microg/mL for S. pneumoniae, < or =0.06microg/mL for penicillin susceptible S. pneumoniae (PSSP) without any change, 0.5-1 microg/mL for penicillin intermediate resistant S. pneumoniae (PISP) with a twofold change and 1 microg/mL for PRSP with no change. The MIC90s of CVA/AMPC (1:14) were 2-8 microg/mL for S. aureus with a fourfold change, 2 microg/mL for methicillin-sensitive S. aureus without any change, 4-8 microg/mL for H. influenzae with a twofold change. Against beta-lactamase non-producing H. influenzae, MIC90s of CVA/AMPC (1:14) were 1 microg/mL for beta-lactamase negative ampicillin susceptible (BLNAS), 8 microg/mL for beta-lactamase negative ampicillin resistant (BLNAR), showing no change. Neither Streptococcus pyogenes or Klebsiella pneumoniae demonstrated any change and M. catarrhalis and Escherichia coli showed twofold changes of MIC90s of CVA/AMPC (1: 14). In the present investigation conducted to monitor annual changes in antibacterial activity intended for pediatric patients with otitis media or other infections, there was no significant change in antibacterial activity of CVA/AMPC (1: 14). PMID:24167843

Ishida, Atsuko; Hasegawa, Naomi; Okano, Hideyuki; Hara, Terufumi; Yoshida, Pascal

2013-06-01

282

Susceptibility patterns of bacterial isolates from hospitalised patients with respiratory tract infections (MOXIAKTIV Study).  

PubMed

The objective of this study was to determine: (i) the prevalence of resistance in current clinical isolates of Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis and Klebsiella pneumoniae; (ii) the prevalence of production of extended-spectrum beta-lactamases (ESBLs) and methicillin resistance in S. aureus; and (iii) regional differences in the prevalence of ESBL production and clonality of K. pneumoniae isolates. Pathogens causing respiratory tract infections in hospitalised patients were prospectively collected from all over Germany. Drugs tested by Etest included moxifloxacin, levofloxacin, amoxicillin/clavulanic acid, cefuroxime, clarithromycin and penicillin G. ESBL production by K. pneumoniae was determined using cefotaxime/ceftazidime +/- clavulanic acid. Deutsches Institut für Normung (German Institute for Standardisation)/European Committee on Antimicrobial Susceptibility Testing (DIN/EUCAST) breakpoints were used where applicable. Overall, 1859 pathogens were analysed. For all species tested the fluoroquinolones achieved the highest overall susceptibility rate (92.8%) compared with clarithromycin (60.5%), amoxicillin/clavulanic acid (85.7%) and cefuroxime (89.6%). From 438 K. pneumoniae isolates, 13.0% produced an ESBL. The ESBL prevalence was 38.8% in Eastern Germany with a trend towards clonality in some centres, but ranged from 4.7% to 7.1% in Southern, Northern and Western Germany. Among the methicillin-susceptible S. aureus isolates, 10.1% were moxifloxacin- and levofloxacin-resistant. Of the S. pneumoniae isolates, 99.3% were moxifloxacin- and levofloxacin-susceptible, 93.9% were penicillin G-susceptible and 85.7% were clarithromycin-susceptible. With a MIC90 value (minimal inhibitory concentration for 90% of the isolates) of 0.19 mg/L, moxifloxacin was more potent than levofloxacin (MIC90 = 1 mg/L) against S. pneumoniae. Haemophilus influenzae and M. catarrhalis were almost 100% susceptible to the quinolones; 100% of the M. catarrhalis but only 4.5% of the H. influenzae strains were clarithromycin-susceptible. Moxifloxacin was the most active agent amongst the drugs tested, in particular against Gram-positive pathogens. PMID:18835763

Jacobs, Enno; Dalhoff, Axel; Korfmann, Gisela

2009-01-01

283

Qualidade de frutos de cinco híbridos de melão rendilhado em função do número de frutos por planta  

Microsoft Academic Search

RESUMO-Este trabalho teve por objetivo avaliar a qualidade de cinco híbridos de melão rendilhado, com dois e três frutos por planta, utilizando fibra da casca de coco e fertirrigação. Para tanto, foi instalado um experimento em casa de vegetação na UNESP-FCAV, Câmpus de Jaboticabal, com delineamento experimental em blocos ao acaso, em esquema fatorial 5 x 2, com quatro repetições.

Renata Castoldi; Hamilton César de Oliveira Charlo; Pablo Forlan Vargas; Leila Trevizan Braz

2008-01-01

284

Estudio Multicentrico de Prevalencia del Trastorno por Déficit de Atención e Hiperactividad en la República Argentina1  

Microsoft Academic Search

El presente es el primer estudio de prevalencia del Trastorno por Déficit de Atención realizado en la República Argentina. Se utilizó una muestra de inicial de 898 niños de 6 a 9 años correspondientes a los tres primeros años de escuelas primarias del Gran Buenos Aires que tras ser depurada quedó conformada por 801 niños de ambos sexos. Metodología: Para

Ruben O. Scandar

285

AVALIAÇÃO TEÓRICA E EXPERIMENTAL DO COMPORTAMENTO DE VIGAS DE CONCRETO ARMADO REFORÇADAS POR MEIO DA PROTENSÃO DE CABOS EXTERNOS  

Microsoft Academic Search

Resumo As patologias apresentadas por algumas estruturas e a necessidade de aumento da capacidade de carga de outras fizeram com que diversas técnicas fossem desenvolvidas para o reforço de vigas de concreto armado. Uma delas é a incorporação e protensão de cabos externos. O grande diferencial desta técnica quando comparada às demais é o seu caráter ativo, ou seja, por

Tatiana Gesteira; Martins de Almeida; João Bento de Hanai

286

Microestructura y propiedades mecánicas de conductores protónicos de alta temperatura crecidos por fusión de zona flotante  

Microsoft Academic Search

Se han estudiado conductores protónicos de alta temperatura (CPAT) fabricados por fusión de zona flotante asistida por láser (SrCe 0.9Y0.1O3-?, SrCe0.8Y0.2O3-?, SrZr0.9Y0.1O3-?, SrZr0.8Y0.2O3-?, Sr3(Ca1.18Nb1.82)O9-? y SrTi0.95Sc0.05O3-?). La caracterización microestructural se ha realizado mediante Microscopía Electrónica de Barrido y Transmisión (MEB, MET). Los materiales tienen una estructura celular, con células de anchuras entre 10-50 µm y regiones intercelulares superiores a 1

M. J. López RobLedo; A. SA

287

ATP for the portable 500 CFM exhauster POR-006 skid D  

SciTech Connect

This Acceptance Test Plan is for a 500 CFM Portable Exhauster POR-006 to be used for saltwell pumping. The Portable Exhauster System will be utilized to eliminate potential flammable gases that may exist within the dome space of the tank. This Acceptance Plan will test and verify that the exhauster meets the specified design criteria, safety requirements, operations requirements, and will provide a record of the functional test results.

Keller, C.M.

1997-07-29

288

Comparação da sensibilidade de bovinos e búfalos à intoxicação por Palicourea marcgravii (Rubiaceae)1  

Microsoft Academic Search

Barbosa J. D., Oliveira C. M. C., Tokarnia C. H. & Riet-Correa F. 2003. (Comparison of the sensibility of cattle and buffaloes to poisoning by Palicourea marcgravii (Rubiaceae).) Comparação da sensibilidade de bovinos e búfalos à intoxicação por Palicourea marcgravii (Rubiaceae). Pesquisa Veterinária Brasileira 23(4):167-172. Escola de Medicina Veterinária, Campus Castanhal, Universidade Federal do Pará, Rua Maximino Porpino 1000, Castanhal,

José Diomedes Barbosa; Carlos Magno; Chaves de Oliveira; Carlos Hubinger

289

ESTIMATIVAS DAS CONSTANTES ELÁSTICAS DA MADEIRA POR MEIO DE ONDAS ULTRA-SONORAS (ULTRA-SOM)  

Microsoft Academic Search

RESUMO: O trabalho tem como principal objetivo estimar as constantes elásticas da madeira, empre- gando-se uma metodologia não destrutiva, de ondas ultra-sonoras (ultra-som). Foram utilizadas madei- ras de quatro espécies: Fava Amargosa (Vataireopsis speciosa), Jequitiba Rosa (Cariniana micran- tha), Peroba d'Água (Rauwolfia paraensis) e Peroba Mico (Aspidosperma macrocarpum). Por meio da determinação das velocidades de propagação das ondas ultra-sonoras, baseando-se

Joaquim Carlos Gonçalez; Ailton Teixeira

290

Sitafloxacin: in bacterial infections.  

PubMed

Sitafloxacin is a fluoroquinolone antibacterial with in vitro activity against a broad range of Gram-positive and -negative bacteria, including anaerobic bacteria, as well as against atypical pathogens. It is approved in Japan for use in a number of bacterial infections caused by sitafloxacin-susceptible strains of Staphylococcus spp., Streptococcus pneumoniae, other Streptococcus spp., Enterococcus spp., Moraxella catarrhalis, Escherichia coli, Citrobacter spp., Klebsiella spp., Enterobacter spp., Serratia spp., Proteus spp., Morganella morganii, Haemophilus influenzae, Pseudomonas aeruginosa, Legionella pneumophila, Peptostreptococcus spp., Prevotella spp., Porphyromonas spp., Fusobacterium spp., Chlamydia trachomatis, Chlamydophila pneumoniae and Mycoplasma pneumoniae. In terms of clinical efficacy, oral sitafloxacin was noninferior to oral levofloxacin in the treatment of community-acquired pneumonia or an infectious exacerbation of chronic respiratory tract disease, noninferior to oral tosufloxacin in the treatment of community-acquired pneumonia, and noninferior to oral levofloxacin in the treatment of complicated urinary tract infections, according to the results of randomized, double-blind, multicentre, noninferiority trials. Noncomparative studies demonstrated the efficacy of oral sitafloxacin in otorhinolaryngological infections, urethritis in men, C. trachomatis-associated cervicitis in women and odontogenic infections. Gastrointestinal disorders and laboratory abnormalities were the most commonly occurring adverse reactions in patients receiving oral sitafloxacin. Adverse reactions reported in sitafloxacin recipients in the active comparator trials were of mild to moderate severity. PMID:21504249

Keating, Gillian M

2011-04-16

291

Pharmacokinetics of cefuroxime axetil and cefaclor: relationship of concentrations in serum to MICs for common respiratory pathogens.  

PubMed Central

The pharmacokinetics of single doses of cefaclor at 250 and 375 mg and cefuroxime axetil at 250 mg administered under optimal conditions (i.e., cefuroxime axetil after food and cefaclor in the fasted state) were studied in 24 healthy male volunteers. Drug concentrations in serum were related to MICs for common respiratory tract pathogens by using data generated from a recently completed national survey. The time the concentrations in serum exceeded the MICs for Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella (formerly Branhamella) catarrhalis were significantly greater (P less than 0.05) for cefuroxime axetil at 250 mg than for cefaclor at 250 or 375 mg. With the recommended dosing regimens (cefuroxime axetil at 250 mg and cefaclor at 375 mg twice daily or cefaclor at 250 mg three times daily), cefuroxime concentrations exceed the MIC for 90% of the strains tested for a greater time period than cefaclor concentrations with either regimen. The reasons for this difference are (i) the greater potency and slower clearance of cefuroxime compared with those of cefaclor and (ii) the greater sensitivity of these pathogens to cefuroxime.

James, N C; Donn, K H; Collins, J J; Davis, I M; Lloyd, T L; Hart, R W; Powell, J R

1991-01-01

292

Pharmacokinetics of cefuroxime axetil suspension in infants and children.  

PubMed Central

The pharmacokinetics of cefuroxime axetil suspension in 28 infants and children, ranging in age from 3 months to 12 years (mean, 23 months), were studied. Mean maximum serum cefuroxime concentrations of 3.3, 5.1, and 7.0 micrograms/ml were achieved 3.6, 2.7, and 3.1 h after the administration of doses of 10, 15, and 20 mg, respectively, of cefuroxime axetil suspension per kg of body weight together with milk or milk formula. These concentrations exceed the MICs for common respiratory tract pathogens, including beta-lactamase-producing strains of Haemophilus influenzae and Moraxella (Branhamella) catarrhalis. Following a 10- or 15-mg/kg dose, serum cefuroxime concentrations are similar to those achieved in adults following the administration of a 250-mg cefuroxime axetil tablet. There were linear relationships between dose and both maximum serum cefuroxime concentration and area under the serum drug concentration-verus-time curve. The mean half-life of cefuroxime in serum was independent of dose and ranged from 1.4 to 1.9 h. No cefuroxime axetil (intact ester) was detected in the blood. The intact ester in the urine of four children was measured; however, the amount recovered represented less than 0.1% of the administered dose.

Powell, D A; James, N C; Ossi, M J; Nahata, M C; Donn, K H

1991-01-01

293

Secondary electrospray ionization-mass spectrometry (SESI-MS) breathprinting of multiple bacterial lung pathogens, a mouse model study.  

PubMed

Bacterial pneumonia is one of the leading causes of disease-related morbidity and mortality in the world, in part because the diagnostic tools for pneumonia are slow and ineffective. To improve the diagnosis success rates and treatment outcomes for bacterial lung infections, we are exploring the use of secondary electrospray ionization-mass spectrometry (SESI-MS) breath analysis as a rapid, noninvasive method for determining the etiology of lung infections in situ. Using a murine lung infection model, we demonstrate that SESI-MS breathprints can be used to distinguish mice that are infected with one of seven lung pathogens: Haemophilus influenzae, Klebsiella pneumoniae, Legionella pneumophila, Moraxella catarrhalis, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae, representing the primary causes of bacterial pneumonia worldwide. After applying principal components analysis, we observed that with the first three principal components (primarily comprised of data from 14 peaks), all infections were separable via SESI-MS breathprinting (P < 0.0001). Therefore, we have shown the potential of this SESI-MS approach for rapidly detecting and identifying acute bacterial lung infections in situ via breath analysis. PMID:23519230

Zhu, Jiangjiang; Bean, Heather D; Jiménez-Díaz, Jaime; Hill, Jane E

2013-06-01

294

Synthesis and antibacterial activities of N-substituted-glycinyl 1H-1,2,3-triazolyl oxazolidinones.  

PubMed

A series of 1H-1,2,3-triazolyl piperazino oxazolidinone analogs with optionally varied glycinyl substitutions were synthesized and their antibacterial activity assessed against a panel of susceptible and resistant Gram-positive and selected Gram-negative bacteria including clinical isolates. The N-aroyl- and N-heteroaroyl-glycinyl (MIC: 0.06-4 ?g/ml) derivatives were more potent than the N-acylglycinyl (2-8 ?g/ml) derivatives against all Gram-positive bacteria tested. Nitro substitution on aryl and heteroaryl rings significantly enhanced activity against Gram-positive bacteria, as noted with the 3,5-dinitrobenzoyl (6m and 6n) and 5-nitro-2-furoyl (6u and 6v) derivatives with MIC ranges of and 0.25-0.5 and 0.06-0.5 ?g/ml, respectively. These nitro analogs also showed more potent extended activity against Moraxella catarrhalis, with MICs ranges of 0.25-1 ?g/ml, compared to linezolid (MIC: 8 ?g/ml). Hence, the presence of the N-aroyl and/or N-heteroaroyl glycinyl structural motifs as spacer group could significantly enhance the antibacterial activities of 1H-1,2,3-triazolyl oxazolidinone class of compounds. PMID:23811087

Phillips, Oludotun A; Udo, Edet E; Abdel-Hamid, Mohammed E; Varghese, Reny

2013-08-01

295

[Antimicrobial spectrum of ceftaroline. In vitro activity against methicillin-resistant staphylococci].  

PubMed

Because of the increase in bacterial resistance, there is a need for new antimicrobial agents. In particular, Staphylococcus aureus is a frequent cause of severe infections and has an extraordinary capacity to develop antibiotic multiresistance, including resistance to glycopeptides, linezolid, and daptomycin. Although the incidence of methicillin-resistant S. aureus (MRSA) seems to have stabilized in the last few years, its wide dissemination in healthcare settings and in the community is a cause of concern. Ceftaroline is a new broad-spectrum cephalosporin with bactericidal activity against Gram-positive bacteria, including MRSA and multidrug-resistant Streptococcus pneumoniae. In addition, this drug is active against staphylococci showing resistance to glycopeptides, linezolid, and daptomycin. The ceftaroline MIC90 against MRSA ranges from 0.5-2mg/L and that against methicillin-resistant coagulase-negative staphylococci is 0.5mg/L. Ceftaroline has also good activity against respiratory pathogens including Haemophilus influenzae and Moraxella catarrhalis. Although this drug is active against Enterobacteriaceae, it does not retain activity when these isolates produce extended-spectrum beta-lactamases, carbapenemases or hyperproduce AmpC. Ceftaroline is not active against nonfermentative Gram-negative bacilli. Ceftaroline is an interesting addition to the therapeutic armamentarium against MRSA and constitutes an important option for the treatment of polymicrobial infections caused by multidrug-resistant Gram-positive microorganisms. PMID:24702973

Cercenado, Emilia; Morosini, María Isabel

2014-03-01

296

Otitis media.  

PubMed

Bacterial pathogens are isolated from middle ear fluid in up to 90% of children with acute otitis media (OM). Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis predominate. Acute OM can be classified as uncomplicated, persistent, recurrent or chronic. Patient age, symptom severity, prior treatment history and exposure through day-care attendance in children influences pathogen distribution, antimicrobial susceptibility and anticipated clinical and microbiological responses to empirical and pathogen-directed therapies. The natural history of acute OM without intervention is favourable. However, meta-analysis of clinical trials shows an improvement in symptom and middle ear effusion resolution with antimicrobials. Aminopenicillins, cephalosporins and macrolides are often selected as therapy for acute OM. The various agents have differing activity against acute OM pathogens, particularly organisms with resistance mechanisms and they differ in dosing schedule, side effects and compliance enhancing factors. Consideration should be given to pharmacokinetic and pharmacodynamic principles in antibiotic selection. Selection criteria include antibiotic activity against drug-resistant S. pneumoniae and efficacy against beta-lactamase-producing Gram-negative organisms. The necessary duration of treatment for acute OM varies according to multiple factors, including local preferences, but there is growing, compelling data to support short-course therapy. Tympanocentesis has been endorsed in various guidelines as a diagnostic and therapeutic procedure. Best-practice for management of acute OM continues to advocate antibiotic therapy with careful, accurate diagnosis and consideration of the major pathogens and their mechanisms of resistance. PMID:12150687

Pichichero, Michael E; Casey, Janet R

2002-08-01

297

Prulifloxacin.  

PubMed

Prulifloxacin, the prodrug of ulifloxacin, is a broad-spectrum oral fluoroquinolone antibacterial agent. After absorption, prulifloxacin is metabolised by esterases to ulifloxacin. The drug has a long elimination half-life, allowing once-daily administration. Ulifloxacin is generally more active in vitro than other fluoroquinolones against a variety of clinical isolates of Gram-negative bacteria, including community and nosocomial isolates of Escherichia coli, Klebsiella spp., Proteus, Providencia and Morganella spp., Moraxella catarrhalis and Haemophilus spp. The activity of ulifloxacin against Pseudomonas aeruginosa varies between countries. Gram-positive organisms, including meticillin- or oxacillin-susceptible Staphylococcus aureus, Enterococcus spp. and Italian community isolates of Streptococcus pneumoniae are susceptible to ulifloxacin. Activity against Spanish strains of S. pneumoniae is moderate. In well designed clinical trials, good clinical and bacteriological efficacy (similar to that of ciprofloxacin, amoxicillin/clavulanic acid or pefloxacin) was seen with prulifloxacin 600 mg once daily for 10 days in patients with acute exacerbations of chronic bronchitis or complicated lower urinary tract infections (UTIs), and with single-dose prulifloxacin 600 mg in acute, uncomplicated lower UTIs. Prulifloxacin was generally well tolerated in clinical trials, with a similar tolerability profile to that of ciprofloxacin. PMID:15456336

Keam, Susan J; Perry, Caroline M

2004-01-01

298

Pathogens in the middle ear effusion of children with persistent otitis media: implications of drug resistance and complications.  

PubMed

Acute otitis media (AOM) is the most common disease for which pediatricians prescribe antimicrobial agents. Middle ear fluid were collected from 243 children with AOM that failed to respond to a previous course of antimicrobial therapy and who had then received myringotomy from September 1997 through August 1999. Bacterial cultures were done and antimicrobial susceptibilities were analyzed. Streptococcus pneumoniae (21.8%) was the most common causative organism, followed by Haemophilus influenzae (10.2%), Staphylococcus aureus (7%), and Pseudomonas aeruginosa (1.8%), while Moraxella catarrhalis (0.7%) and group A beta-hemolytic streptococcus (0.2%) were rarely isolated. In patients whose condition failed to improve after a course of antibiotic treatment, drug resistance became a serious problem. Fourteen percent of the patients in this series had complications, which included recurrent AOM, persistent middle ear effusion necessitating ventilation tube insertion, hearing impairment, mastoiditis, meningitis, chronic otitis media, brain abscess, and sepsis. Possible risk factors such as young age, male sex, underlying diseases, and a culture of S. pneumoniae or H. influenzae were not significantly associated with an increased incidence of complications. More stringent diagnosis and the correct choice of antibiotic treatment combined with the introduction of potential virus and bacterial vaccines are promising ways to reduce the morbidity of AOM in children. PMID:11605810

Li, W C; Chiu, N C; Hsu, C H; Lee, K S; Hwang, H K; Huang, F Y

2001-09-01

299

The use and resistance to antibiotics in the community.  

PubMed

The frequency of resistance to antibiotics among common community-acquired pathogens, and the number of drugs to which they are resistant have been increasing worldwide. The relationship between antibiotic usage and resistance is strongly supported by data from several studies. Countries with the highest per capita antibiotic consumption have the highest resistance. The emergence of penicillin-resistant Streptococcus pneumoniae is related to high consumption of antibiotics in general, as well as to increased use of aminopenicillins and/or probably to wider use of oral cephalosporins. Increased consumption of macrolides, especially the long-acting ones, correlates significantly with the level of macrolide resistance of group A streptococci and S. pneumoniae while increased use of oral cephalosporins might be associated with the increase of beta-lactamase-producing strains of Moraxella catarrhalis. Trimethoprim/sulphamethoxazole resistance is strongly associated with resistance to penicillin. A rise in consumption of fluoroquinolones is consonant with a higher rate of resistance to quinolones of S. pneumoniae, Escherichia coli and other Gram-negative bacteria. Paediatric bacterial isolates are more often resistant to various antimicrobial agents than isolates from adult patients; this higher resistance rate may be due to more frequent antimicrobial treatments in children, and extensive child to child transmission. Reliable data on antimicrobial consumption and resistance should form a basis for national policies devised to reduce the resistance of microorganisms to antibiotics. PMID:12672574

Cizman, Milan

2003-04-01

300

Viruses and bacteria in sputum samples of children with community-acquired pneumonia.  

PubMed

Few comprehensive studies have searched for viruses and bacteria in children with community-acquired pneumonia (CAP). We identified 76 children hospitalized for pneumonia. Induced sputum samples were analysed for 18 viruses by antigen detection and PCR, and for six bacteria by culture and PCR. Viruses were found in 72% of samples, bacteria in 91%, and both in 66%. Rhinovirus (30%), human bocavirus (18%) and human metapneumovirus (14%) were the most commonly detected viruses. Two viruses were found in 22% of samples and three in 8%. The most common bacteria found were Streptococcus pneumoniae (50%), Haemophilus influenzae (38%), and Moraxella catarrhalis (28%). Rhinovirus-S. pneumoniae was the most commonly found combination of virus and bacterium (16%). All six children with treatment failure had both viruses and bacteria detected in the sputum. Otherwise, we found no special clinical characteristics in those with mixed viral-bacterial detections. With modern molecular diagnostic techniques, there are high rates of both viral and bacterial identification in childhood CAP. The clinical significance of mixed viral-bacterial infections remains unclear, although we found a potential association between them and treatment failure. PMID:21851481

Honkinen, M; Lahti, E; Österback, R; Ruuskanen, O; Waris, M

2012-03-01

301

Clinical efficacy of new antibacterial therapies in at-risk populations.  

PubMed

Infections of the lower respiratory tract, such as community-acquired pneumonia (CAP) and acute bacterial exacerbations of chronic bronchitis (AECB), comprise the more serious respiratory tract infections (RTIs), and are associated with considerable morbidity and mortality, particularly in groups such as the very young, the elderly and those with co-morbid illness. Up to 80% of community-acquired RTIs are caused by Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis and are usually treated empirically. However, antibacterial resistance among common respiratory tract pathogens currently threatens the usefulness of existing therapies. The new ketolide antibacterial, telithromycin, has been developed specifically to provide optimal empirical treatment of community-acquired RTIs in the face of widespread antibacterial resistance. Telithromycin 800 mg once-daily offers efficacy equivalent to currently available antibacterials in the treatment of lower RTIs. Moreover, telithromycin demonstrates excellent activity in the treatment of CAP and AECB patients at risk for increased morbidity and mortality, including elderly patients, those with severe infections, and those with CAP complicated by pneumococcal bacteraemia. Telithromycin is also extremely effective in the treatment of patients with lower RTIs caused by atypical and intracellular pathogens (such as Mycoplasma pneumoniae, Legionella pneumophila and Chlamydophila [Chlamydia] pneumoniae--increasingly recognized as important aetiological agents of RTIs, particularly CAP), or by pathogens resistant to beta-lactams and macrolides. Telithromycin therefore represents a promising new agent for the empirical treatment of community-acquired RTIs. PMID:12150492

Lorenz, J

2002-02-01

302

In vitro activity of L-627, a new carbapenem.  

PubMed

The in vitro activity of L-627, a new parenterally administered carbapenem, was compared with those of imipenem, meropenem, FCE 22101 (a penem), ceftazidime, and ceftriaxone. L-627 was active against members of the family Enterobacteriaceae (MIC for 90% of strains tested [MIC90] ranging from 0.03 to 4 micrograms/ml). L-627 displayed activity equal to that of meropenem against Pseudomonas aeruginosa (MIC90, 2 micrograms/ml), although, as with other carbapenems, the antipseudomonal activity was reduced against D2-deficient strains. Staphylococci and streptococci were susceptible (MIC90 of 1.0 micrograms/ml for Staphylococcus aureus and 0.015 micrograms/ml for group A streptococci). L-627 also had activity against anaerobic bacteria (MIC90, 2.0 micrograms/ml for Bacteroides fragilis). Neisseria gonorrhoeae and Neisseria meningitidis were highly susceptible (MIC90, 0.06 micrograms/ml), and against the common respiratory pathogens (Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis), the MIC90s were less than or equal to 2.0 micrograms/ml. The protein binding of L-627 ranged from 13.8 to 22%, depending on the concentration. The presence of human serum had little effect on the MIC or MBC of L-627. These results suggest that L-627 merits further study in the treatment of infections caused by a wide range of pathogens. PMID:1416883

Catchpole, C R; Wise, R; Thornber, D; Andrews, J M

1992-09-01

303

Detection of Streptococcus pneumoniae in sputum samples by PCR.  

PubMed

A method for the detection of Streptococcus pneumoniae in sputum samples by PCR has been developed. The assay employs oligonucleotide primers specific for a portion of the autolysin gene lytA of S. pneumoniae. Other closely related streptococci, Haemophilus influenzae, and Moraxella catarrhalis do not give a positive result in the assay. The assay was capable of detecting between 10 and 100 CFU of S. pneumoniae in distilled water and 1.4 x 10(4) CFU/ml in simulated sputum samples. Sputum samples from 33 patients with acute pneumonia were collected and subjected to culture, PCR, and C-polysaccharide antigen detection by enzyme-linked immunosorbent assay (ELISA). A significant isolate of S. pneumoniae was isolated from 14 patients, of which 13 were positive by PCR and C-polysaccharide antigen ELISA. No positive results were obtained for the 19 patients in whom other pathogens or upper respiratory tract floras only were isolated. The sensitivity of the autolysin PCR is 92.8%, the specificity is 100%, the predictive value of a positive result is 100%, and the predictive value of a negative result is 95%. This suggests that autolysin PCR is suitable for the detection of S. pneumoniae in clinical samples. PMID:7914205

Gillespie, S H; Ullman, C; Smith, M D; Emery, V

1994-05-01

304

In vitro activity of RU 29246, the active compound of the cephalosporin prodrug ester HR 916.  

PubMed

The in vitro activity of RU 29246 was compared with those of other agents against 536 recent clinical isolates. The MICs of RU 29246 for 90% of members of the family Enterobacteriaceae tested (MIC90s) were less than 2 micrograms/ml except those for Morganella spp. (16 micrograms/ml) and Proteus spp. (8 micrograms/ml). RU 29246 was active against Staphylococcus aureus (MIC90, < or = 8 micrograms/ml) and against Staphylococcus saprophyticus and coagulase-negative staphylococci (MIC90s, < or = 2 micrograms/ml). Streptococci and Neisseria gonorrhoeae were highly susceptible to RU 29246, and the activity of the agent against isolates of Streptococcus pneumoniae (MIC90, < or = 0.5 micrograms/ml), Haemophilus influenzae (MIC90, < or = 2 micrograms/ml), and Moraxella catarrhalis (MIC90, < or = 2 micrograms/ml) was comparable to those of the other cephalosporins tested. RU 29246 was insusceptible to hydrolysis by the common plasmid-mediated beta-lactamases (TEM-1 and SHV-1). However, hydrolysis by the new extended-spectrum beta-lactamases (TEM-3, TEM-5, and TEM-9) was detected. Results of the study suggested that RU 29246 should be investigated clinically for use in the treatment of a wide range of infections. PMID:1489178

Riess, G; Andrews, J; Thornber, D; Wise, R

1992-11-01

305

Ceftaroline: a comprehensive update.  

PubMed

Ceftaroline is a novel broad-spectrum cephalosporin antibiotic currently under US Food and Drug Administration (FDA) review for a new drug application (NDA), filed by Cerexa, Inc. (a wholly owned subsidiary of Forest Laboratories), for the treatment of complicated skin and skin-structure infections (cSSSIs) and community-associated pneumonia (CAP). The antibiotic acts by binding to penicillin-binding proteins in bacteria, consistent with other ?-lactams. The antimicrobial spectrum of ceftaroline ranges from aerobic and anaerobic Gram-positive bacteria, including drug-resistant isolates of staphylococci, i.e. heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA), vancomycin-intermediate S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA), to anaerobic Gram-negative pathogens such as Moraxella catarrhalis and Haemophilus influenzae (including ?-lactamase-positive strains), as well as bacteria with multiple resistance phenotypes. Ceftaroline fosamil is the prodrug that is rapidly dephosphorylated by in vivo plasma phosphatases to the active drug ceftaroline, which follows a two-compartmental pharmacokinetic model and is eliminated primarily by renal excretion, with a plasma half-life of ca. 2.5 h. Ceftaroline is well tolerated, which is consistent with its good safety profile similar to other cephalosporins in clinical trials. Thus, it would be a promising drug to fight multidrug-resistant superbugs such as S. aureus and Streptococcus pneumoniae for the treatment of cSSSIs and CAP. PMID:21420284

Kaushik, Darpan; Rathi, Sudeep; Jain, Ankit

2011-05-01

306

Genetic characteristics of Haemophilus influenzae and Streptococcus pneumoniae isolated from children with conjunctivitis-otitis media syndrome.  

PubMed

Acute conjunctivitis is the most common ocular disorders among children and frequently concomitant with acute otitis media (AOM) as conjunctivitis-otitis syndrome. In this study, we evaluated prevalence of causative pathogens and PCR-based genotypes of Haemophilus influenzae and Streptococcus pneumoniae among children with conjunctivitis-otitis media syndrome. Nontypeable H. influenzae (NTHi) is identified most often at 61.8% in conjunctiva exudates followed by S. pneumoniae at 28.2% and Moraxella catarrhalis at 19.1%. Genetic ?-lactamase nonproducing ampicillin resistant (gBLNAR) strains of NTHi and genetic penicillin resistant S. pneumoniae (gPRSP) were identified at 72.1% and at 74.2% among conjunctiva isolates by polymerase chain reaction (PCR), respectively. Pneumococcal strains having either ermB or mefE genes were identified at 93.5% among conjunctiva isolates. The restriction fragment of patterns of 89.7% pairs of H. influenzae isolates and 100% pairs of pneumococcal isolates from conjunctiva exudates, middle ear fluids (MEFs) and nasopharyngeal swabs were identical. In contrast to the previous reports, most prevalent strains from conjunctivitis-otitis media syndrome was BLNAR H. influenzae in this study. The causative pathogen responsible for acute conjunctivitis will be originated from the nasopharynx. In the absence of MEFs one can possibly rely on the nasopharyngeal culture to guide an appropriate treatment. PMID:24953451

Sugita, Gen; Hotomi, Muneki; Sugita, Rinya; Kono, Masamitsu; Togawa, Akihisa; Yamauchi, Kazuma; Funaki, Toshinari; Yamanaka, Noboru

2014-08-01

307

Rationale for treating community-acquired lower respiratory tract infections with amoxicillin/sulbactam combination through pharmacodynamic analysis in the setting of aminopenicillin-resistant organisms.  

PubMed

In order to establish a rationale for treating community-acquired lower respiratory tract infections, we assess here the pharmacodynamics of amoxicillin/sulbactam, 500mg/500mg, a formulation marketed in Argentina since 1988 and currently available in 17 countries, against the major pathogens, in comparison with that of a novel formulation (875mg/125mg, see J Chemother 2000; 12: 223-227). In time-kill studies, both bactericidal and inhibitory activity were seen in the 1.5- and 6-h sera, obtained from 12 volunteers after a single oral dose, against both a penicillin-susceptible and an -intermediate Streptococcus pneumoniae strain, as well as against Moraxella catarrhalis and a beta-lactamase-negative Haemophilus influenzae strain. Only the 1.5-h sera proved bactericidal against a penicillin-resistant S. pneumoniae strain (MIC, 2 microg/ml) and a beta-lactamse-positive H. influenzae isolate. This study suggests that amoxicillin/sulbactam (500mg/500mg) is still a suitable option for treating community-acquired lower respiratory tract infections, allowing a b.i.d. dosing schedule. Caution should be taken with pneumonia caused by beta-lactamase-positive H. influenzae or penicillin-resistant (MIC > or =2 microg/ml) S. pneumoniae isolates. Either shorter dosing intervals (t.i.d.) or a higher amoxicillin content in the formulation (i.e. 875 mg) may be required in these situations. PMID:11589483

Bantar, C; Nicola, F; Fernandez Canigia, L; Arenoso, H J; Soutric, J; Montoto, M; Blanco, M; Smayevsky, J; Jasovich, A

2001-08-01

308

Bacterial Infection in Chronic Obstructive Pulmonary Disease in 2000: a State-of-the-Art Review  

PubMed Central

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States. The precise role of bacterial infection in the course and pathogenesis of COPD has been a source of controversy for decades. Chronic bacterial colonization of the lower airways contributes to airway inflammation; more research is needed to test the hypothesis that this bacterial colonization accelerates the progressive decline in lung function seen in COPD (the vicious circle hypothesis). The course of COPD is characterized by intermittent exacerbations of the disease. Studies of samples obtained by bronchoscopy with the protected specimen brush, analysis of the human immune response with appropriate immunoassays, and antibiotic trials reveal that approximately half of exacerbations are caused by bacteria. Nontypeable Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae are the most common causes of exacerbations, while Chlamydia pneumoniae causes a small proportion. The role of Haemophilus parainfluenzae and gram-negative bacilli remains to be established. Recent progress in studies of the molecular mechanisms of pathogenesis of infection in the human respiratory tract and in vaccine development guided by such studies promises to lead to novel ways to treat and prevent bacterial infections in COPD.

Sethi, Sanjay; Murphy, Timothy F.

2001-01-01

309

Fragment-to-hit-to-lead discovery of a novel pyridylurea scaffold of ATP competitive dual targeting type II topoisomerase inhibiting antibacterial agents.  

PubMed

The discovery and optimization of a new class of bacterial topoisomerase (DNA gyrase and topoisomerase IV) inhibitors binding in the ATP domain are described. A fragment molecule, 1-ethyl-3-(2-pyridyl)urea, provided sufficiently potent enzyme inhibition (32 ?M) to prompt further analogue work. Acids and acid isosteres were incorporated at the 5-pyridyl position of this fragment, bridging to a key asparagine residue, improving enzyme inhibition, and leading to measurable antibacterial activity. A CF3-thiazole substituent at the 4-pyridyl position improved inhibitory potency due to a favorable lipophilic interaction. Promising antibacterial activity was seen versus the Gram-positive pathogens Staphylococcus aureus and Streptococcus pneumoniae and the Gram-negative pathogens Haemophilus influenzae and Moraxella catarrhalis . Precursor metabolite incorporation and mutant analysis studies support the mode-of-action, blockage of DNA synthesis by dual target topoisomerase inhibition. Compound 35 was efficacious in a mouse S. aureus disease model, where a 4.5-log reduction in colony forming units versus control was demonstrated. PMID:24098982

Basarab, Gregory S; Manchester, John I; Bist, Shanta; Boriack-Sjodin, P Ann; Dangel, Brian; Illingworth, Ruth; Sherer, Brian A; Sriram, Shubha; Uria-Nickelsen, Maria; Eakin, Ann E

2013-11-14

310

Ceftaroline: A New Cephalosporin with Activity against Methicillin-Resistant Staphylococcus aureus (MRSA)  

PubMed Central

Microbial resistance has reached alarming levels, threatening to outpace the ability to counter with more potent antimicrobial agents. In particular, methicillin-resistant Staphylococcus aureus (MRSA) has become a leading cause of skin and soft-tissue infections and PVL-positive strains have been associated with necrotizing pneumonia. Increasing reports of growing resistance to glycopeptides have been noted, further limiting the efficacy of standard antibiotics, such as vancomycin. Ceftaroline is a novel fifth-generation cephalosporin, which exhibits broad-spectrum activity against Gram-positive bacteria, including MRSA and extensively-resistant strains, such as vancomycin-intermediate S. aureus (VISA), heteroresistant VISA (hVISA), and vancomycin-resistant S. aureus (VRSA). In addition to being an exciting new agent in the anti-MRSA armamentarium, ceftaroline provides efficacy against many respiratory pathogens including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Ceftaroline (600 mg intravenously every 12 hours) has been shown effective in phase III studies in the treatment of complicated skin and soft tissue infections and community-acquired pneumonia. To date, this unique antibiotic exhibits a low propensity for inducing resistance and has a good safety profile, although further post-marketing data and clinical experience are needed. In summary, ceftaroline provides an additional option for the management of complex multidrug resistant infections, including MRSA.

Duplessis, Christopher; Crum-Cianflone, Nancy F.

2011-01-01

311

Human rhinovirus infection during naturally occurring COPD exacerbations.  

PubMed

Human rhinovirus (HRV) infection is an important trigger of exacerbations of chronic obstructive pulmonary disease (COPD) but its role in determining exacerbation frequency phenotype or the time-course of HRV infection in naturally occurring exacerbations is unknown. Sputum samples from 77 patients were analysed by real-time quantitative PCR for both HRV (388 samples), and Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis (89 samples). Patients recorded worsening of respiratory symptoms on daily diary cards, from which exacerbations were identified. HRV prevalence and load at exacerbation presentation were significantly higher than in the stable state (prevalence 53.3% versus 17.2%, respectively; p<0.001) but 0% by day 35 post-exacerbation. HRV load was higher in patients with cold symptoms (p=0.046) or sore throats (p=0.006) than those without. 73% of bacterium-negative but HRV-positive exacerbations were bacterium-positive by day 14. Patients with HRV detected at exacerbation had a higher exacerbation frequency (interquartile range) of 3.01 (2.02-5.30) per year compared with patients without HRV (2.51 (2.00-3.51)) (p=0.038). HRV prevalence and load increased at COPD exacerbation, and resolved during recovery. Frequent exacerbators were more likely to experience HRV infection. Secondary bacterial infection is common after HRV infection, and provides a possible mechanism for exacerbation recurrence and a potential target for novel therapies. PMID:24627537

George, Sîobhán N; Garcha, Davinder S; Mackay, Alexander J; Patel, Anant R C; Singh, Richa; Sapsford, Raymond J; Donaldson, Gavin C; Wedzicha, Jadwiga A

2014-07-01

312

Identification and characterization of the bacterial etiology of clinically problematic acute otitis media after tympanocentesis or spontaneous otorrhea in German children  

PubMed Central

Background Acute Otitis Media (AOM) is an important and common disease of childhood. Bacteria isolated from cases of clinically problematic AOM in German children were identified and characterized. Methods In a prospective non-interventional study in German children between 3 months and less than 60 months of age with Ear, Nose and Throat Specialist –confirmed AOM, middle ear fluid was obtained by tympanocentesis (when clinically indicated) or by careful sampling of otorrhea through/at an existing perforation. Results In 100 children with severe AOM, Haemophilus influenzae was identified in 21% (18/21, 85.7% were non-typeable [NTHi]), Streptococcus pneumoniae in 10%, S. pyogenes in 13% and Moraxella catarrhalis in 1%. H. influenzae was the most frequently identified pathogen in children from 12 months of age. H. influenzae and S. pneumoniae were equally prevalent in children aged 3–11 months, but S. pyogenes was most frequently isolated in this age group. NTHi AOM disease appeared prevalent in all ages. Conclusions NTHi, S. pneumoniae and S. pyogenes are implicated as important causes of complicated AOM in children in Germany. NTHi disease appears prevalent in all ages. The impact of vaccination to prevent NTHi and S. pneumoniae AOM may be substantial in this population and is worth investigating.

2012-01-01

313

Se calcula que los costos del cáncer ascenderán por lo menos a $158.000 millones en 2020  

Cancer.gov

Con base en el crecimiento y en el avance de edad de la población de EE. UU., se proyecta que los gastos médicos por cáncer en el año 2020 ascenderán por lo menos a $158.000 millones (en dólares de 2010); lo que significa un aumento de 27% sobre 2010. Si los instrumentos creados últimamente para diagnosticar, tratar y seguir observando el cáncer continúan subiendo de precio, los gastos médicos por cáncer podrían ascender hasta $207.000 millones. Las proyecciones están basadas en los datos más recientes disponibles acerca de la incidencia del cáncer, de supervivencia y de costos de atención médica.

314

Análise dos Conceitos Astronômicos Apresentados por Professores de Algumas Escolas Estaduais Brasileiras  

NASA Astrophysics Data System (ADS)

A razão para o desenvolvimento deste trabalho baseia-se no fato de que muitos professores da Educação Básica (EB) não lidam com conceitos relacionados à astronomia, e quando o fazem eles simplesmente seguem livros didáticos que podem conter erros conceituais. Como é de conhecimento geral a astronomia é um dos conteúdos a serem ensinados na EB fazendo parte dos Parâmetros Curriculares Nacionais e das Propostas Curriculares do Estado de São Paulo, mas é um fato, que vários pesquisadores apontam, a existência de muitos problemas no ensino da astronomia. Com o propósito de minimizar algumas dessas deficiências foi realizado um trabalho de pesquisa com a utilização de questionários pré e pós pesquisa, para tanto foi desenvolvido um Curso de Extensão Universitária para professores da Diretoria de Ensino Regional (DE) que abrange Mauá, Ribeirão Pires e Rio Grande da Serra (no Estado de São Paulo) com os seguintes objetivos: levantar concepções alternativas; subsidiar os professores por meio de palestras, debates e workshops, e verificar o sucesso da aprendizagem após o curso, adotando-se como referência, para a análise dos resultados, os dicionários de Língua Portuguesa (FERREIRA, 2004) e Enciclopédico de Astronomia e Astronáutica (MOUR?O, 1995). Portanto, dezesseis questões foram aplicadas antes e após o curso, assim pode-se verificar após a pesquisa que 100,0% dos professores sabiam os nomes das fases da Lua, 97,0% entenderam que o Sistema Solar é composto por oito planetas, 78,1% foram capazes de explicar como ocorre um eclipse lunar, um eclipse solar e um solstício, 72,7% sabiam como explicar a ocorrência das estações do ano; 64,5% explicaram corretamente a ocorrência do equinócio, 89,7% foram capazes de definir adequadamente o termo cometa; 63,6% definiram asteróide, 54,5% meteoro, 58,1% galáxia, e 42,4% planeta. Os resultados obtidos indicam uma aprendizagem significativa por parte dos participantes.

Voelzke, Marcos Rincon; Gonzaga, Edson Pereira

2011-12-01

315

Characterization of Plasmid pOR1 from Ornithobacterium rhinotracheale and Construction of a Shuttle Plasmid  

PubMed Central

The bacterium Ornithobacterium rhinotracheale has been recognized as an emerging pathogen in poultry since about 10 years ago. Knowledge of this bacterium and its mechanisms of virulence is still very limited. Here we report the development of a transformation system that enables genetic modification of O. rhinotracheale. The system is based on a cryptic plasmid, pOR1, that was derived from an O. rhinotracheale strain of serotype K. Sequencing indicated that the plasmid consisted of 14,787 nucleotides. Sequence analysis revealed one replication origin and several rep genes that control plasmid replication and copy number, respectively. In addition, pOR1 contains genes with similarity to a heavy-metal-transporting ATPase, a TonB-linked siderophore receptor, and a laccase. Reverse transcription-PCR demonstrated that these genes were transcribed. Other putative open reading frames exhibited similarities with a virulence-associated protein in Actinobacillus actinomycetemcomitans and a number of genes coding for proteins with unknown function. An Escherichia coli-O. rhinotracheale shuttle plasmid (pOREC1) was constructed by cloning the replication origin and rep genes from pOR1 and the cfxA gene from Bacteroides vulgatus, which codes for resistance to the antibiotic cefoxitin, into plasmid pGEM7 by using E. coli as a host. pOREC1 was electroporated into O. rhinotracheale and yielded cefoxitin-resistant transformants. The pOREC1 isolated from these transformants was reintroduced into E. coli, demonstrating that pOREC1 acts as an independent replicon in both E. coli and O. rhinotracheale, fulfilling the criteria for a shuttle plasmid that can be used for transformation, targeted mutagenesis, and the construction of defined attenuated vaccine strains.

Jansen, Ruud; Chansiripornchai, Niwat; Gaastra, Wim; van Putten, Jos P. M.

2004-01-01

316

Antigenic topology of chlamydial PorB protein and identification of targets for immune neutralization of infectivity.  

PubMed

The outer membrane protein PorB is a conserved chlamydial protein that functions as a porin and is capable of eliciting neutralizing Abs. A topological antigenic map was developed using overlapping synthetic peptides representing the Chlamydia trachomatis PorB sequence and polyclonal immune sera. To identify which antigenic determinants were surface accessible, monospecific antisera were raised to the PorB peptides and were used in dot-blot and ELISA-based absorption studies with viable chlamydial elementary bodies (EBs). The ability of the surface-accessible antigenic determinants to direct neutralizing Ab responses was investigated using standardized in vitro neutralization assays. Four major antigenic clusters corresponding to Phe(34)-Leu(59) (B1-2 and B1-3), Asp(112) -Glu(145) (B2-3 and B2-4), Gly(179)-Ala(225) (B3-2 to B3-4), and Val(261)-Asn(305) (B4-4 to B5-2) were identified. Collectively, the EB absorption and dot-blot assays established that the immunoreactive PorB Ags were exposed on the surface of chlamydial EBs. Peptide-specific antisera raised to the surface-accessible Ags neutralized chlamydial infectivity and demonstrated cross-reactivity to synthetic peptides representing analogous C. pneumoniae PorB sequences. Furthermore, neutralization of chlamydial infectivity by C. trachomatis PorB antisera was inhibited by synthetic peptides representing the surface-exposed PorB antigenic determinants. These findings demonstrate that PorB Ags may be useful for development of chlamydial vaccines. PMID:11994474

Kawa, Diane E; Stephens, Richard S

2002-05-15

317

Trazodona: ¿Nuevo enfoque selectivo para el tratamiento de los sofocos generados por la deprivación androgénica en el carcinoma prostático?  

Microsoft Academic Search

toxicidad nada despreciable. Dentro del tratamiento no hormonal de esta patología juegan un papel destacado los antidepresivos. Latrazodona,unantidepresivoSARI(inhibidoresdelarecaptacióndeserotonina\\/antagonistadela2A),conunperfildeactua - ciónmásselectivosobrelosreceptoresimplicadosenlossofocos;podríaserdegraninterés.Trazodonamuestraunagranafinidad por los receptores 5-HT 2A y una moderada afinidad por los receptores 5-HT 1A. Comoesconocidolosnivelesdeserotonina(5-hidroxitriptaminao5-HT)enmujerespostmenopáusicasestándisminuidos,nor - malizándoseconlasterapiassustitutivas.Todoellosugierequeladeprivaciónabruptadehormonassexualesdalugaraunareduc - ción en la circulación de serotonina, con el consiguiente aumento de sus receptores 5-HT 2A hipotalámicos. Estos receptores esta - rían implicados

Santiago Vilar González; Francesc Montañá Puig; Sebastiá Sabater Martí; Manuel Aguayo Martos

2009-01-01

318

A DNA Fusion Vaccine Induces Bactericidal Antibodies to a Peptide Epitope from the PorA Porin of Neisseria meningitidis?  

PubMed Central

An experimental DNA plasmid vaccine was developed based on a well-characterized and protective peptide epitope derived from a bacterial porin protein. For this study, we used the P1.16b serosubtype epitope, located in variable region (VR)2 in loop 4 of the PorA outer membrane (OM) porin from Neisseria meningitidis serogroup B strain MC58. A plasmid that encoded the entire loop (pPorAloop4) was prepared, as well as a fusion plasmid that encoded the loop in tandem with the fragment C (FrC) immunostimulatory sequence from tetanus toxin (pPorAloop4-FrC). The constructs were used for intramuscular immunization without exogenous adjuvant. Murine antisera raised to the pPorAloop4-FrC DNA fusion plasmid reacted significantly with OMs in enzyme-linked immunosorbent assay and with whole bacteria by immunofluorescence, whereas antisera raised to the pPorAloop4 DNA plasmid and to control plasmid showed little or no reactivity. Significantly, only the pPorALoop4-FrC plasmid induced bactericidal antibodies, demonstrating that the intrinsic immunostimulatory sequence was essential for inducing a protective immune response. The antibodies raised to the P1.16b pPorALoop4-FrC plasmid were serosubtype specific, showing no significant immunofluorescence reactivity or bactericidal activity against other PorA variants. These data provide proof of principle for a DNA fusion plasmid strategy as a novel approach to preparing vaccines based on defined, protective epitopes.

Zhu, Delin; Williams, Jeannette N.; Rice, Jason; Stevenson, Freda K.; Heckels, John E.; Christodoulides, Myron

2008-01-01

319

Aplicação do Método de Monte Carlo, GEANT 4 e SRIM 2003 no Projeto de um Tomógrafo por Feixe Prótons de Baixa Energia  

Microsoft Academic Search

Resumo - A radioterapia por feixe de prótons é uma alternativa altamente eficiente no tratamento do câncer. Atualmente, nos centros de tratamento por prótons, o cálculo de dose é baseada em imagens de tomografia computadorizadas de raio-x (CT) e o paciente é posicionado com auxílio de radiografias de raio-x. A alternativa proposta é a utilização da tomografia por feixe de

J. A. P. Setti; E. Milhoretto; S. R. Junior; H. R. Schelin; M. C. L. Klock; V. Denyak; R. Rocha; I. Evseev; O. Yevseyeva

320

Effect of SPM-based cleaning POR on EUV mask performance  

NASA Astrophysics Data System (ADS)

EUV masks include many different layers of various materials rarely used in optical masks, and each layer of material has a particular role in enhancing the performance of EUV lithography. Therefore, it is crucial to understand how the mask quality and patterning performance can change during mask fabrication, EUV exposure, maintenance cleaning, shipping, or storage. The fact that a pellicle is not used to protect the mask surface in EUV lithography suggests that EUV masks may have to undergo more cleaning cycles during their lifetime. More frequent cleaning, combined with the adoption of new materials for EUV masks, necessitates that mask manufacturers closely examine the performance change of EUV masks during cleaning process. We have investigated EUV mask quality and patterning performance during 30 cycles of Samsung's EUV mask SPM-based cleaning and 20 cycles of SEMATECH ADT exposure. We have observed that the quality and patterning performance of EUV masks does not significantly change during these processes except mask pattern CD change. To resolve this issue, we have developed an acid-free cleaning POR and substantially improved EUV mask film loss compared to the SPM-based cleaning POR.

Choi, Jaehyuck; Lee, Han-Shin; Yoon, Jinsang; Shimomura, Takeya; Friz, Alex; Montgomery, Cecilia; Ma, Andy; Goodwin, Frank; Kang, Daehyuk; Chung, Paul; Shin, Inkyun; Cho, H.

2011-10-01

321

Substrate-specific modulation of CYP3A4 activity by genetic variants of cytochrome P450 oxidoreductase (POR)  

PubMed Central

Objectives CYP3A4 receives electrons from P450 oxidoreductase (POR) to metabolize about 50% of clinically used drugs. There is substantial inter-individual variation in CYP3A4 catalytic activity that is not explained by CYP3A4 genetic variants. CYP3A4 is flexible and distensible, permitting it to accommodate substrates varying in shape and size. To elucidate mechanisms of variability in CYP3A4 catalysis, we examined the effects of genetic variants of POR, and explored the possibility that substrate-induced conformational changes in CYP3A4 differentially affect the ability of POR variants to support catalysis. Methods We expressed human CYP3A4 and four POR variants (Q153R, A287P, R457H, A503V) in bacteria, reconstituted them in vitro and measured the Michaelis constant and maximum velocity with testosterone, midazolam, quinidine and erythromycin as substrates. Results POR A287P and R457H had low activity with all substrates; Q153R had 76–94% of wild type (WT) activity with midazolam and erythromycin, but 129–150% activity with testosterone and quinidine. The A503V polymorphism reduced CYP3A4 activity to 61–77% of wild type with testosterone and midazolam, but had nearly wild type activity with quinidine and erythromycin. Conclusion POR variants affect CYP3A4 activities. The impact of a POR variant on catalysis by CYP3A4 is substrate-specific, probably due to substrate-induced conformational changes in CYP3A4.

Agrawal, Vishal; Choi, Ji Ha; Giacomini, Kathleen M.; Miller, Walter L.

2010-01-01

322

Fabrication of por-Si/SnO{sub x} nanocomposite layers for gas microsensors and nanosensors  

SciTech Connect

Two-phase nanocomposite layers based on porous silicon and nonstoichiometric tin oxide were fabricated by various methods. The structure, as well as elemental and phase composition, of the obtained nanocomposites were studied using transmission and scanning electron microscopy, Raman spectroscopy, Auger electron spectroscopy, and X-ray photoelectron spectroscopy. The results obtained confirm the formation of nanocomposite layers with a thickness as large as 2 {mu}m thick and SnO{sub x} stoichiometry coefficients x = 1.0-2.0. Significant tin diffusion into the porous silicon matrix with D{sub eff} Almost-Equal-To 10{sup -14} cm{sup 2} s{sup -1} was observed upon annealing at 770 K. Test sensor structures based on por-Si/SnO{sub x} nanocomposite layers grown by magnetron deposition showed fairly high stability of properties and sensitivity to NO{sub 2}.

Bolotov, V. V., E-mail: bolotov@obisp.oscsbras.ru; Korusenko, P. M.; Nesov, S. N.; Povoroznyuk, S. N.; Roslikov, V. E.; Kurdyukova, E. A.; Sten'kin, Yu. A.; Shelyagin, R. V.; Knyazev, E. V.; Kan, V. E.; Ponomareva, I. V. [Russian Academy of Sciences, Rzhanov Institute of Semiconductor Physics, Omsk Branch, Siberian Branch (Russian Federation)

2011-05-15

323

Impact of PPARA and POR polymorphisms on tacrolimus pharmacokinetics and new-onset diabetes in kidney transplant recipients.  

PubMed

Recent efforts have been made to identify genetic markers of CYP3A4 enzymatic activity within genes encoding for regulatory elements. The aim of the current study was to investigate the impact of polymorphism of PPARA and POR genes on tacrolimus (TAC) dose-adjusted trough concentration and risk of new-onset diabetes after transplantation (NODAT). A total of 241 White kidney transplant patients were genotyped for three functional single nucleotide polymorphisms: rs1057868 (*28) in POR, rs4253728:G>A, and rs4823613:A>G in PPARA. No significant genotype-dependent differences in TAC dose-adjusted trough concentration were observed for either POR or PPARA variants. No significant differences in the incidence of NODAT were observed between patients stratified by PPARA and POR genotypes. The frequency of NODAT among PPARA rs4253728 AA homozygotes (42%) was higher compared with heterozygotes (22%) and GG homozygotes (19%), but the difference was not significant. Testing TAC-medicated renal transplant recipients for POR and PPARA variants seems to have limited clinical application. PMID:24921414

Kurzawski, Mateusz; Malinowski, Damian; Dziewanowski, Krzysztof; Dro?dzik, Marek

2014-08-01

324

Antitumor actinopyranones produced by Streptomyces albus POR-04-15-053 isolated from a marine sediment.  

PubMed

Four new antitumor pyranones, PM050511 (1), PM050463 (2), PM060054 (3), and PM060431 (4), were isolated from the cell extract of the marine-derived Streptomyces albus POR-04-15-053. Their structures were elucidated by a combination of spectroscopic methods, mainly 1D and 2D NMR and HRESIMS. They consist of an ?-methoxy-?-pyrone ring containing a highly substituted tetraene side chain glycosylated at C-10 in the case of 1 and 4. Compounds 1 and 4 displayed strong cytotoxicity against three human tumor cell lines with GI?? values in the submicromolar range, whereas 2 showed subnanomolar activity as an inhibitor of EGFR-MAPK-AP1-mediated mitogenic signaling, causing inhibition of EGF-mediated AP1 trans-activation and EGF-mediated ERK activation and slight inhibition of EGF-mediated JNK activation. Taken together, these results suggest that members of the pyranone family of compounds could be developed as potential antitumor agents. PMID:21718029

Schleissner, Carmen; Pérez, Marta; Losada, Alejandro; Rodríguez, Pilar; Crespo, Cristina; Zúñiga, Paz; Fernández, Rogelio; Reyes, Fernando; de la Calle, Fernando

2011-07-22

325

Comparación de resultados del método de clasificación de órbitas por análisis de frecuencias con el método de exponentes de Lyapunov  

NASA Astrophysics Data System (ADS)

Hemos realizado extensas comparaciones del método de análisis de frecuencias con el de exponentes de Lyapunov. El primero resulta claramente superior por las siguientes razones: 1) permite distinguir distintos tipos de órbitas y no sólo si son regulares o caóticas 2) es mucho más veloz requiriendo mucho menos tiempo de cómputo. La concordancia de resultados es, en general, buena y se discuten algunas discrepancias.

Carpintero, D. D.; Muzzio, J. C.; Wachlin, F. C.

326

INFLUENCIA DE LA MICROESTRUCTURA Y DE LOS ESTADOS TRIAXIALES DE TENSIONES EN FENÓMENOS DE FISURACIÓN INDUCIDA POR AMBIENTE  

Microsoft Academic Search

Resumen. La Fisuración Inducida por Hidrógeno (FIH), es uno de los fenómenos de corrosión bajo tensión más habitual en aquellas aplicaciones industriales que se encuentran en contacto con este elemento químico, como sucede en oleoductos, gasoductos, reactores de hydrotreating, etc. Existen numerosos estudios referentes al transporte y acumulación de hidrógeno en el metal, así como a la variación de propiedades

A. Cayón; J. A. Álvarez; F. Gutiérrez-Solana

2003-01-01

327

Estado actual del pretratamiento de las intoxicaciones por agentes neuro- tóxicos de guerra con piridostigmina y otras alternativas farmacológicas  

Microsoft Academic Search

Resumen: El bromuro de piridostigmina (bromuro de 3-dimeti- laminocarboniloxi-N-metilpiridinio) se utiliza como pretrata- miento en escenarios en los que existe riesgo de utilización de agentes neurotóxicos de guerra. De hecho, este pretratamiento fue utilizado por las tropas Aliadas durante la Guerra del Golfo Pérsico. Desde su vuelta a casa muchos veteranos de esta guerra se han quejado de padecer síntomas

Pita R; Martínez-Larrañaga

328

UMA ANÁLISE DOS ASPECTOS DISTRIBUTIVOS DA APOSENTADORIA POR TEMPO DE CONTRIBUIÇÃO DO INSS COM O EMPREGO DE MATEMÁTICA ATUARIAL  

Microsoft Academic Search

O objetivo do artigo é o cálculo de parâmetros usualmente adotados na literatura sobre previdência social, como as taxas de reposição previdenciária, alíquotas de contribuição atuarialmente justa e valores presentes de contribuições e de benefícios, para o caso brasileiro. Os cálculos são feitos para a Aposentadoria por Tempo de Contribuição (ATC) do Regime Geral de Previdência Social (RGPS) do INSS.

Daniela de Almeida Lima; Luís Eduardo Afonso

2010-01-01

329

PRIMER REPORTE SOBRE FOTOSENSIBILIZACION CAUSADA POR Pithomices chartarum EN BORREGOS PASTOREANDO Brachiaria brizantha. EN LA ZONA CENTRO DEL ESTADO DE TAMAULIPAS  

Microsoft Academic Search

RESUMEN: La creciente explosión demográfica, sobre todo en los países subdesarrollados, como lo es México, se han dado a la tarea de aumentar los productos alimentarios de origen animal por citar un ejemplo, la explotación de ovinos, mismo que a su vez se buscan nuevas alternativas para su alimentación, sobre todo con costos mínimos, por ello la utilización de recursos

O. S. Escamilla Gallegos; P. Zárate Fortuna; M. Rodríguez Morales; J. García Jiménez; M. González

330

MODELO EXPERIMENTAL DE FORMAÇÃO DE VARIZES ESOFÁGICAS POR HIPERTENSÃO PORTAL ESQUISTOSSOMÓTICA EM HAMSTERS EXPERIMENTAL MODEL OF ESOPHAGEAL VARICES' FORMATION IN SCHISTOSOMAL PORTAL HYPERTENSION  

Microsoft Academic Search

RESUMO: Objetivo: Desenvolver um modelo experimental de formação de varizes esofágicas por hipertensão portal esquistossomótica em hamsters. Método: Utilizamos 55 hamsters divididos em dois grupos: grupo I composto de 50 animais infectados com injeção percutânea de 100 cercarias de Schistosoma mansoni da cepa BH; e grupo II composto de cinco animais sadios (grupo de controle). Foram mantidos por um período

José Cesar Assef; Adriana Christina; Pozzobon de Oliveira Vieira; Hellen Christina; Garcia Saito; Carmen Lúcia Penteado Lancellotte; Luiz Arnaldo Szutan

331

The PorB porin from commensal Neisseria lactamica induces Th1 and Th2 immune responses to ovalbumin in mice and is a potential immune adjuvant  

PubMed Central

Porins from pathogenic Neisseriae are among several bacterial products with immune adjuvant activity. N. meningitidis (Nme) PorB, has been shown to induce immune cells activation in a TLR2-dependent manner and acts as a vaccine immune adjuvant. The PorB porin from Neisseria lactamica (Nlac), a common nasopharyngeal commensal shares significant structural and functional similarities with Nme PorB. In this work we ask whether the immune adjuvant ability of porins from pathogenic Neisserial strains is a characteristic shared with porins from non-pathogenic Neisserial species or whether it is unique for bacterial products derived from microorganisms capable of inducing inflammation and disease. We evaluate the potential immune adjuvant effect of Nlac PorB in mice using ovalbumin (OVA) as a prototype antigen. Immunization with Nlac PorB/OVA induced high OVA-specific IgG and IgM titers compared to OVA alone, similar to other adjuvants such as Nme PorB and alum. High titers of IgG1 and IgG2b were detected as well as production of IL-4, IL-10, IL-12 and INF-? in response to Nlac PorB, consistent with induction of both a Th1-type and a Th2-type immune response. OVA-specific proliferation was also determined in splenocytes from Nlac PorB/OVA immunized mice. In addition, B cell activation in vitro and cytokine production in response to Nlac PorB was found to be mediated by TLR2, in a similar manner to Nme PorB.

Liu, Xiuping; Wetzler, Lee M.; Massari, Paola

2008-01-01

332

Evolução da morfologia de fases de blendas PA6\\/AES em extrusora de dupla rosca e moldagem por injeção  

Microsoft Academic Search

Resumo: A evolução da morfologia de fases em blendas não reativas e reativas de poliamida-6 com copolímero de acrilonitrila\\/EPDM\\/estireno (AES) em uma extrusora de rosca dupla co-rotacional foi investigada. A evolução da morfologia de fases ao longo da extrusora de rosca dupla foi monitorada através da coleta de pequenas amostras em válvulas no barril da extrusora e caracterização por microscopia

Adriane Bassani; Elias Hage Jr; Luiz A. Pessan; Ana V. Machado; José A. Covas

2005-01-01

333

Estudio sobre las dosis de radiación y los riesgos de cáncer causados por la prueba atómica “Trinity” realizada en 1945  

Cancer.gov

El NCI tiene planeado realizar entrevistas en profundidad para determinar cuál era la alimentación característica de las poblaciones indígenas americanas, hispanas (latinas) y chicanas que vivían en New Mexico a mediados de 1940 y utilizar información fácilmente disponible sobre la alimentación y el estilo de vida de las poblaciones blancas. Estas entrevistas representan un paso importante para hacer estimaciones de las dosis de radiación generadas por la prueba Trinity.

334

Nasopharyngeal flora in children with acute otitis media before and after implementation of 7 valent pneumococcal conjugate vaccine in France  

PubMed Central

Background Several studies have investigated the impact of 7-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal (Sp) and staphylococcal (Sa) nasopharyngeal (NP) carriage. Few have investigated the impact on Haemophilus influenzae (Hi) and Moraxella catarrhalis (Mc) carriage. We aimed to compare the NP carriage rates in young children with acute otitis media (AOM) before and after PCV7 implementation in France. Methods Prior to PCV7 implementation, we performed 4 successive randomized trials with NP samples. These studies compared several antibiotic regimens for treating AOM in young children (6 to 30 months). After PCV7 implementation, to assess the impact of the vaccination program on NP flora, young children with AOM were enrolled in a prospective surveillance study. In each study, we obtained an NP sample to analyze the carriage rates of Sp, Hi, Mc and Sa and the factors influencing the carriage. Standardized history and physical examination findings were recorded; the methods used for NP swabs (sampling and cultures) were the same in all studies. Results We enrolled 4,405 children (mean age 13.9 months, median 12.8). Among the 2,598 children enrolled after PCV7 implementation, 98.3% were vaccinated with PCV7. In comparing the pre- and post-PCV7 periods, we found a slight but non-significant decrease in carriage rates of pneumococcus (AOR = 0.85 [0.69;1.05]), H. influenzae (AOR = 0.89 [0.73;1.09]) and S. aureus (AOR = 0.92 [0.70;1.19]). By contrast, the carriage rate of M. catarrhalis increased slightly but not significantly between the 2 periods (AOR = 1.08 [0.95;1.2]). Among Sp carriers, the proportion of PCV7 vaccine types decreased from 66.6% to 10.7% (P < 0.001), penicillin intermediate-resistant strains increased from 30.3% to 43.4% (P < 0.001), and penicillin-resistant strains decreased greatly from 22.8% to 3.8% (P < 0.001). The proportion of Hi ß-lactamase-producing strains decreased from 38.6% to 17.1% (P < 0.001). Conclusion The carriage rates of otopathogen species (Sp, Hi, Mc) and Sa did not significantly change in children with AOM after PCV7 implementation in France. However, we observed significant changes in carriage rates of PCV7 vaccine serotypes and penicillin non-susceptible Sp.

2012-01-01

336

Voltage dependent closure of PorB class II porin from Neisseria meningitidis investigated using impedance spectroscopy in a tethered bilayer lipid membrane interface.  

PubMed

Electrochemical impedance spectroscopy (EIS) was used to characterize voltage-dependent closure of PorB class II (PorBII) porin from Neisseria meningitidis incorporated in a tethered bilayer lipid membrane (tBLM). The tBLM's lower leaflet was fabricated by depositing a self assembled monolayer (SAM) of 1,2-dipalmitoyl-sn-glycero-3-phosphothioethanol (DPPTE) on a gold electrode, and the upper leaflet was formed by depositing1,2-dioleoyl-sn-glycero-3-phoshocholine (DOPC) liposomes. At 0mV bias DC potential, incorporation of PorBII decreased the membrane resistance (R(m)) from 2.5 M?c m(2) to 0.6 M? cm(2), giving a ?R(m) of 1.9 M? cm(2) and a normalized ?R(m) (?R(m) divided by the R(m) of the tBLM without PorBII) of 76%. When the bias DC potential was increased to 200 mV, the normalized ?R(m) value decreased to 20%. The effect of applied voltage on ?R(m) was completely reversible, suggesting voltage-dependent closure of PorBII. The voltage dependence of PorBII was further studied in a planar bilayer lipid membrane made from 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhytPC). Following a single insertion event, PorBII exhibited multiple conductance states, with reversible, voltage-dependent closure of PorBII porin occurring at high transmembrane potentials. The trimetric porin closed in three discrete steps, each step corresponding to closure of one conducting monomer unit. The most probable single channel conductance was 4.2 nS. The agreement between results obtained with the tBLM and pBLM platforms demonstrates the utility of EIS to screen channel proteins immobilized in tBLM for voltage-gated behavior. PMID:23083768

Jadhav, Sachin R; Rao, Kota Sreenivasa; Zheng, Yi; Garavito, R Michael; Worden, R Mark

2013-01-15

337

In vitro antibacterial activity of doripenem against clinical isolates from French teaching hospitals: proposition of zone diameter breakpoints.  

PubMed

The aims of the study were to determine the in vitro activity of doripenem, a new carbapenem, against a large number of bacterial pathogens and to propose zone diameter breakpoints for clinical categorization in France according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) minimum inhibitory concentration (MIC) breakpoints. The MICs of doripenem were determined by the broth microdilution method against 1,547 clinical isolates from eight French hospitals. The disk diffusion test was performed (10-?g discs) according to the Comité de l'Antibiogramme de la Société Française de Microbiologie (CASFM) method. The MIC(50/90) (mg/L) values were as follows: methicillin-susceptible Staphylococcus aureus (MSSA) (0.03/0.25), methicillin-resistant Staphylococcus aureus (MRSA) (1/2), methicillin-susceptible coagulase-negative staphylococci (MSCoNS) (0.03/0.12), methicillin-resistant coagulase-negative staphylococci (MRCoNS) (2/8), Streptococcus pneumoniae (0.016/0.25), viridans group streptococci (0.016/2), ?-hemolytic streptococci (?0.008/?0.008), Enterococcus faecalis (2/4), Enterococcus faecium (128/>128), Enterobacteriaceae (0.06/0.25), Pseudomonas aeruginosa (0.5/8), Acinetobacter baumannii (0.25/2), Haemophilus influenzae (0.12/0.25), and Moraxella catarrhalis (0.03/0.06). According to the regression curve, the zone diameter breakpoints were 24 and 19 mm for MICs of 1 and 4 mg/L, respectively. This study confirms the potent in vitro activity of doripenem against Pseudomonas aeruginosa, Acinetobacter, Enterobacteriaceae, MSSA, MSCoNS, and respiratory pathogens. According to the EUCAST MIC breakpoints (mg/L) ?1/>4 for Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter, and ?1/>1 for streptococci, pneumococci, and Haemophilus, the zone diameter breakpoints could be (mm) ?24/<19 and ?24/<24, respectively. PMID:21088861

Lascols, C; Legrand, P; Mérens, A; Leclercq, R; Armand-Lefevre, L; Drugeon, H B; Kitzis, M D; Muller-Serieys, C; Reverdy, M E; Roussel-Delvallez, M; Moubareck, C; Lemire, A; Miara, A; Gjoklaj, M; Soussy, C-J

2011-04-01

338

In vitro antibacterial activity of ceftobiprole against clinical isolates from French teaching hospitals: proposition of zone diameter breakpoints.  

PubMed

The aims of this study were to determine the in vitro activity profile of ceftobiprole, a pyrrolidinone cephalosporin, against a large number of bacterial pathogens and to propose zone diameter breakpoints for clinical categorisation according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) minimum inhibitory concentration (MIC) breakpoints. MICs of ceftobiprole were determined by broth microdilution against 1548 clinical isolates collected in eight French hospitals. Disk diffusion testing was performed using 30 ?g disks according to the method of the Comité de l'Antibiogramme de la Société Française de Microbiologie (CA-SFM). The in vitro activity of ceftobiprole, expressed by MIC(50/90) (MICs for 50% and 90% of the organisms, respectively) (mg/L), was as follows: meticillin-susceptible Staphylococcus aureus, 0.25/0.5; meticillin-resistant S. aureus (MRSA), 1/2; meticillin-susceptible coagulase-negative staphylococci (CoNS), 0.12/0.5; meticillin-resistant CoNS, 1/2; penicillin-susceptible Streptococcus pneumoniae, ? 0.008/0.03; penicillin-resistant S. pneumoniae, 0.12/0.5; viridans group streptococci, 0.03/0.12; ?-haemolytic streptococci, ? 0.008/0.016; Enterococcus faecalis, 0.25/1; Enterococcus faecium, 64/128; Enterobacteriaceae, 0.06/32; Pseudomonas aeruginosa, 4/16; Acinetobacter baumannii, 0.5/64; Haemophilus influenzae, 0.03/0.12; and Moraxella catarrhalis, 0.25/0.5. According to the regression curve, zone diameter breakpoints could be 28, 26, 24 and 22 mm for MICs of 0.5, 1, 2 and 4 mg/L respectively. In conclusion, this study confirms the potent in vitro activity of ceftobiprole against many Gram-positive bacteria, including MRSA but not E. faecium, whilst maintaining a Gram-negative spectrum similar to the advanced-generation cephalosporins such as cefepime. Thus ceftobiprole appears to be well suited for the empirical treatment of a variety of healthcare-associated infections. PMID:21295447

Lascols, C; Legrand, P; Mérens, A; Leclercq, R; Muller-Serieys, C; Drugeon, H B; Kitzis, M D; Reverdy, M E; Roussel-Delvallez, M; Moubareck, C; Brémont, S; Miara, A; Gjoklaj, M; Soussy, C-J

2011-03-01

339

Diagnosis of tuberculosis by trained African giant pouched rats and confounding impact of pathogens and microflora of the respiratory tract.  

PubMed

Trained African giant-pouched rats (Cricetomys gambianus) can detect Mycobacterium tuberculosis and show potential for the diagnosis of tuberculosis (TB). However, rats' ability to discriminate between clinical sputum containing other Mycobacterium spp. and nonmycobacterial species of the respiratory tract is unknown. It is also unknown whether nonmycobacterial species produce odor similar to M. tuberculosis and thereby cause the detection of smear-negative sputum. Sputum samples from 289 subjects were analyzed by smear microscopy, culture, and rats. Mycobacterium spp. were isolated on Lowenstein-Jensen medium, and nonmycobacterial species were isolated on four different media. The odor from nonmycobacterial species from smear- and M. tuberculosis culture-negative sputa detected by ?2 rats ("rat positive") was analyzed by gas chromatography-mass spectrometry and compared to the M. tuberculosis odor. Rats detected 45 of 56 confirmed cases of TB, 4 of 5 suspected cases of TB, and 63 of 228 TB-negative subjects (sensitivity, 80.4%; specificity, 72.4%; accuracy, 73.9%; positive predictive value, 41.7%; negative predictive value, 93.8%). A total of 37 (78.7%) of 47 mycobacterial isolates were M. tuberculosis complex, with 75.7% from rat-positive sputa. Ten isolates were nontuberculous mycobacteria, one was M. intracellulare, one was M. avium subsp. hominissuis, and eight were unidentified. Rat-positive sputa with Moraxella catarrhalis, Streptococcus pneumoniae, Staphylococcus spp., and Enterococcus spp. were associated with TB. Rhodococcus, Nocardia, Streptomyces, Staphylococcus, and Candida spp. from rat-positive sputa did not produce M. tuberculosis-specific volatiles (methyl nicotinate, methyl para-anisate, and ortho-phenylanisole). Prevalence of Mycobacterium-related Nocardia and Rhodococcus in smear-negative sputa did not equal that of smear-negative mycobacteria (44.7%), of which 28.6% were rat positive. These findings and the absence of M. tuberculosis-specific volatiles in nonmycobacterial species indicate that rats can be trained to specifically detect M. tuberculosis. PMID:22135255

Mgode, Georgies F; Weetjens, Bart J; Nawrath, Thorben; Cox, Christophe; Jubitana, Maureen; Machang'u, Robert S; Cohen-Bacrie, Stéphan; Bedotto, Marielle; Drancourt, Michel; Schulz, Stefan; Kaufmann, Stefan H E

2012-02-01

340

HIRA-TAN: a real-time PCR-based system for the rapid identification of causative agents in pneumonia.  

PubMed

Identification of the causative pathogen(s) of pneumonia would allow the selection of effective antibiotics and thus reduce the mortality rate and the emergence of drug-resistant pathogens. To identify such pathogens and to obtain these benefits, it is necessary that a clinical test is rapid, accurate, easily performed, and cost-effective. Here, we devised a PCR-based test, named HIRA-TAN, which is able to discriminate therapeutic targets from commensal organisms (e.g. Streptococcus pneumoniae or Haemophilus influenzae) and to detect foreign organisms (e.g. Mycoplasma pneumoniae or Legionella pneumophila) in the sputum. The utility of this system was validated in a prospective study, using sputum samples from patients with pneumonia. 568 patients were enrolled and the HIRA-TAN assay identified the causative pathogens with an accuracy of 96.7% for H. influenzae; 93.2% for Pseudomonas aeruginosa; 80.6% for Klebsiella pneumoniae; 90.9% for Moraxella catarrhalis; 87.5% for Escherichia coli; 78.1% for MRSA and 91.6% for S. pneumoniae. Overall the HIRA-TAN procedure was able to identify the causative pathogens of pneumonia in 60% of the cases. Additionally, this procedure was able to determine when the pneumonia-causing organism was a commensal organism or a foreign organism in a single assay. The HIRA-TAN approach yielded reproducible results and provided valuable information to plan the course of treatment of pneumonia. Through the rapid identification of the causative pathogens, the HIRA-TAN will promote targeted treatments for pneumonias. Clinical Trials Registration: UMIN000001694. PMID:24411834

Hirama, Takashi; Minezaki, Shohei; Yamaguchi, Takefumi; Kishi, Etsuko; Kodama, Keiji; Egashira, Hiroshi; Kobayashi, Kunihiko; Nagata, Makoto; Ishii, Toshiaki; Nemoto, Manabu; Tanaka, Masahiko; Fukunaga, Koichi; Kanazawa, Minoru; Hagiwara, Koichi

2014-02-01

341

Ceftaroline fosamil: a review of its use in the treatment of complicated skin and soft tissue infections and community-acquired pneumonia.  

PubMed

Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil (Zinforo, Teflaro), is an advanced-generation, parenteral cephalosporin with broad-spectrum antibacterial activity in vitro against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and multidrug resistant Streptococcus pneumoniae and Gram-negative bacteria, including Haemophilus influenzae and Moraxella catarrhalis, but not Pseudomonas aeruginosa. Ceftaroline has demonstrated a low potential for the selection of resistance in vitro for drug-resistant Gram-positive organisms, including MRSA, as well as for Gram-negative respiratory pathogens. In pivotal phase III studies, intravenous ceftaroline fosamil demonstrated noninferiority to intravenous vancomycin plus aztreonam in patients hospitalized with complicated skin and soft tissue infections (cSSTIs) and intravenous ceftriaxone in patients hospitalized with community-acquired pneumonia (CAP) [Pneumonia Outcomes Research Team (PORT) risk class III or IV]; however, patients with CAP admitted to the intensive care unit were not evaluated. Ceftaroline fosamil was generally well tolerated in these trials, with an adverse event profile similar to that of other cephalosporins. Diarrhoea was the most commonly reported adverse event; however, the risk of Clostridium difficile-associated diarrhoea with ceftaroline fosamil appeared to be low. Potential limitations of the drug include the lack of an oral formulation and the requirement for twice-daily administration. Nonetheless, ceftaroline fosamil represents an attractive option (either alone or in combination with other agents) for the initial empirical treatment of patients hospitalized with cSSTIs (including those with suspected MRSA infection) or CAP (PORT risk class III or IV) who require intravenous antimicrobial therapy. As with all antibacterial agents, ceftaroline fosamil should be used in accordance with good antimicrobial stewardship. PMID:23801418

Frampton, James E

2013-07-01

342

Nonantibiotic macrolides prevent human neutrophil elastase-induced mucus stasis and airway surface liquid volume depletion.  

PubMed

Mucus clearance is an important component of the lung's innate defense system. A failure of this system brought on by mucus dehydration is common to both cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Mucus clearance rates are regulated by the volume of airway surface liquid (ASL) and by ciliary beat frequency (CBF). Chronic treatment with macrolide antibiotics is known to be beneficial to both CF and COPD patients. However, chronic macrolide usage may induce bacterial resistance. We have developed a novel macrolide, 2'-desoxy-9-(S)-erythromycylamine (GS-459755), that has significantly diminished antibiotic activity against Staphylococcus aureus, Streptococcus pneumonia, Moraxella catarrhalis, and Haemophilus influenzae. Since neutrophilia frequently occurs in chronic lung disease and human neutrophil elastase (HNE) induces mucus stasis by activating the epithelial sodium channel (ENaC), we tested the ability of GS-459755 to protect against HNE-induced mucus stasis. GS-459755 had no effect on HNE activity. However, GS-459755 pretreatment protected against HNE-induced ASL volume depletion in human bronchial epithelial cells (HBECs). The effect of GS-459755 on ASL volume was dose dependent (IC?? ~3.9 ?M) and comparable to the antibacterial macrolide azithromycin (IC?? ~2.4 ?M). Macrolides had no significant effect on CBF or on transepithelial water permeability. However, the amiloride-sensitive transepithelial voltage, a marker of ENaC activity, was diminished by macrolide pretreatment. We conclude that GS-459755 may limit HNE-induced activation of ENaC and may be useful for the treatment of mucus dehydration in CF and COPD without inducing bacterial resistance. PMID:23542952

Tarran, Robert; Sabater, Juan R; Clarke, Tainya C; Tan, Chong D; Davies, Catrin M; Liu, Jia; Yeung, Arthur; Garland, Alaina L; Stutts, M Jackson; Abraham, William M; Phillips, Gary; Baker, William R; Wright, Clifford D; Wilbert, Sibylle

2013-06-01

343

Clinical and bacteriological efficacy of the ketolide telithromycin against isolates of key respiratory pathogens: a pooled analysis of phase III studies.  

PubMed

A pooled analysis of data from 13 phase III studies of telithromycin in the treatment of community-acquired pneumonia, acute exacerbations of chronic bronchitis, acute sinusitis or group A beta-haemolytic streptococcal pharyngitis and tonsillitis was undertaken. Causative key respiratory tract pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Streptococcus pyogenes) were isolated at entry to the studies from cultures of relevant respiratory samples and tested for their susceptibility to telithromycin, penicillin and macrolides (erythromycin A). The combined clinical and bacteriological efficacy of telithromycin at the post-therapy, test-of-cure visit (days 17-24) was assessed in patients from whom a microbiologically evaluable pathogen was isolated at entry. More than 98% of key respiratory pathogens isolated, including penicillin G- and macrolide (erythromycin A)-resistant strains of S. pneumoniae, demonstrated full or intermediate susceptibility to telithromycin in vitro at the breakpoints of < or = 1.0 mg/L (susceptible) and 2.0 mg/L (intermediate) used for the purpose of evaluating the susceptibility of isolates recovered during the clinical trials. Treatment with telithromycin 800 mg once-daily for 5, 7 or 7-10 days resulted in high rates of clinical cure (88.5%) and a satisfactory bacteriological outcome (88.9%), similar to the figures seen with comparator antibacterial agents. Clinical cure and eradication rates were good for all key respiratory pathogens, including penicillin G- and macrolide (erythromycin A)-resistant S. pneumoniae. The results suggest that telithromycin will provide effective empirical therapy for community-acquired upper and lower respiratory tract infections. PMID:14706083

Low, D E; Brown, S; Felmingham, D

2004-01-01

344

Five-day moxifloxacin therapy compared with 7-day co-amoxiclav therapy for the treatment of acute exacerbation of chronic bronchitis.  

PubMed

In this randomized, non-blinded study, the efficacy and safety of a 5-day course of moxifloxacin (one 400 mg tablet daily) was compared with that of co-amoxiclav (one 625 mg tablet every 8h) for 7 days, for the treatment of acute exacerbations of chronic bronchitis (AECB). A total of 162 patients with clear signs of an acute exacerbation of chronic bronchitis were enrolled. Of these, 153 could be studied. Seventy-nine patients were randomized in the moxifloxacin arm and 74 in the co-amoxiclav arm of the study. The primary efficacy parameter was clinical response at 14 days in the evaluable population. A clinical success was classified as resolution or improvement of symptoms. Variables used to assess clinical response included wheeze, cough, dyspnoea, sputum volume, rales and ronchi. The success rate in the moxifloxacin group was 88.6% (70 of 79) and that for co-amoxiclav group was 89.2% (66 of 74). At follow-up (28-35 days post-treatment), the continued clinical cure rates were 90.0% (63 of 70) for moxifloxacin and 89.4% (59 of 66) for co-amoxiclav. No significant differences were detected between the two groups. A total of 78 pathogenic bacteria were isolated from the sputum samples of the patients, with Moraxella catarrhalis, Haemophilus influenzae and Streptococcus pneumoniae being the most frequently isolated pathogens. The eradication rate at 14 days in the valid patients was similar for both groups, 90.9% (20 of 22) for the moxifloxacin group and 90.0% (18 of 20) for the co-amoxiclav group. Both drugs were well tolerated with no differences in the drug-related adverse effects or the patients withdrawing because of an adverse event. These results and the good spectrum of antibacterial activity make moxifloxacin a promising and also safe alternative for the empirical treatment of AECB. PMID:15013037

Starakis, I; Gogos, C A; Bassaris, H

2004-02-01

345

Impact of recent antibiotics on nasopharyngeal carriage and lower airway infection in Indigenous Australian children with non-cystic fibrosis bronchiectasis.  

PubMed

Indigenous Australian children have increased rates of bronchiectasis. Despite a lack of high-level evidence on effectiveness and antibiotic resistance, these children often receive long-term antibiotics. In this study, we determined the impact of recent macrolide (primarily azithromycin) and ?-lactam antibiotic use on nasopharyngeal colonisation, lower airway infection (>10(4) CFU/mL of bronchoalveolar lavage fluid culture) and antibiotic resistance in non-typeable Haemophilus influenzae (NTHi), Streptococcus pneumoniae and Moraxella catarrhalis isolates from 104 Indigenous children with radiographically confirmed bronchiectasis. Recent antibiotic use was associated with significantly reduced nasopharyngeal carriage, especially of S. pneumoniae in 39 children who received macrolides [odds ratio (OR)=0.22, 95% confidence interval (CI) 0.08-0.63] and 26 children who received ?-lactams (OR=0.07, 95% CI 0.01-0.32), but had no significant effect on lower airway infection involving any of the three pathogens. Children given macrolides were significantly more likely to carry (OR=4.58, 95% CI 1.14-21.7) and be infected by (OR=8.13, 95% CI 1.47-81.3) azithromycin-resistant S. pneumoniae. Children who received ?-lactam antibiotics may be more likely to have lower airway infection with ?-lactamase-positive ampicillin-resistant NTHi (OR=4.40, 95% CI 0.85-23.9). The risk of lower airway infection by antibiotic-resistant pathogens in children receiving antibiotics is of concern. Clinical trials to determine the overall benefit of long-term antibiotic therapy are underway. PMID:22819151

Hare, K M; Leach, A J; Morris, P S; Smith-Vaughan, H; Torzillo, P; Bauert, P; Cheng, A C; McDonald, M I; Brown, N; Chang, A B; Grimwood, K

2012-10-01

346

Bacteriological findings and antimicrobial resistance in odontogenic and non-odontogenic chronic maxillary sinusitis.  

PubMed

The main objectives of this study were to estimate the frequency of chronic maxillary sinusitis of dental origin, and to evaluate the microbiology of odontogenic and non-odontogenic chronic maxillary sinusitis. Aspirates from 59 patients with chronic maxillary sinusitis (47 non-odontogenic, 12 odontogenic), collected during a 3-year period, were microbiologically processed for aerobic and anaerobic bacteria. Moreover, antimicrobial susceptibility was evaluated in the isolated bacteria. In this study, 20?% of chronic maxillary sinusitis cases were associated with a dental origin, and sinus lift procedures were the main aetiological factor. Our microbiological findings showed that all specimens from chronic maxillary sinusitis were polymicrobial. Sixty aerobes and 75 anaerobes were recovered from the 47 cases of non-odontogenic sinusitis (2.9 bacteria per specimen); 15 aerobes and 25 anaerobes were isolated from the 12 patients with odontogenic sinusitis (3.3 bacteria per specimen). The predominant aerobes were Staphylococcus aureus (27) and Streptococcus pneumoniae (16), while the more frequent anaerobes were Peptostreptococcus species (31) and Prevotella species (30). Haemophilus influenzae and Moraxella catarrhalis were absent in sinusitis associated with a dental origin. Overall, 22?% of Staphylococcus aureus isolates were oxacillin-resistant, and 75?% of Streptococcus pneumoniae isolates were penicillin-resistant and/or erythromycin-resistant; 21?% of anaerobic Gram-positive bacteria were penicillin-resistant, and 44?% of anaerobic Gram-negative bacteria were ?-lactamase-positive. Vancomycin and quinopristin-dalfopristin had the highest in vitro activity against Staphylococcus aureus and Streptococcus species, respectively; amoxicillin-clavulanate and cefotaxime showed the highest in vitro activity against aerobic Gram-negative bacteria; and moxifloxacin, metronidazole and clindamycin were the most active against anaerobic bacteria. PMID:21498651

Puglisi, Salvatore; Privitera, Salvatore; Maiolino, Luigi; Serra, Agostino; Garotta, Matteo; Blandino, Giovanna; Speciale, Annamaria

2011-09-01

347

[Analysis on the sensitivity to beta-lactam antibiotics of respiratory-infectious isolates on the second survey on the sensitivity of isolates conducted by the Japanese Society of Chemotherapy in 2007--concerning the aspect of PK/PD break points].  

PubMed

Sensitivity to beta-lactam antibiotics of isolates clinically obtained from respiratory infection sites in adults on the second survey on sensitivity of isolates conducted by the Japanese Society of Chemotherapy in 2007 was investigated according to the classification of the "Guideline for treatment for adult nosocomial pneumonia in 2008". Among the primary antibacterial drugs for mild (A) and moderate (B) nosocomial pneumonia in adults, beta-lactam antibiotics; ceftriaxone (CTRX), sulbactam/ampicillin (SBT/ABPC), panipenem/betamipron (PAPM/BP), tazobactam/piperacillin (TAZ/PIPC), imipenem/cilastatin (IPM/CS), meropenem (MEPM), doripenem (DRPM), biapenem (BIPM) were studied to evaluate their clinical efficacy. The covering rate was analyzed using the minimal inhibitory concentration (MIC) and break point of pharmacokinetics/pharmacodynamics (PK/PD). Consequently, the results with methicillin-susceptible Staphylococcus aureus (MSSA), Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Klebsiella pneumoniae revealed the MIC90 of all antibacterial drugs to be at low levels, while almost 100% of isolates were within the range of PK/PD break points except BIPM and SBT/ABPC to H. influenzae, and SBT/ABPC to K. pneumoniae. However, the analysis of P. aeruginosa didn't reach 100% for the covering rates of isolates, indicating that these drugs did not have a complete inhibitory action to restrict bacterial proliferation. The analysis of all 5 carbapenem drugs showed superiority to TAZ/PIPC in MIC90 while covering rates of isolates at PK/PD break points showed inferiority to TAZ/PIPC. This tendency was found to be more significant in covering the rates of isolates on the regular dose with maximal bactericidal action and on the maximum dose. This is because the maximum dose approved in Japan is as low as half that in IPM/CS and 1/3 that in MEPM in Western countries. PMID:19882981

Niki, Yoshihito; Kohno, Shigeru; Watanabe, Akira; Aoki, Nobuki

2009-06-01

348

High detection rates of nucleic acids of a wide range of respiratory viruses in the nasopharynx and the middle ear of children with a history of recurrent acute otitis media.  

PubMed

Both bacteria and viruses play a role in the development of acute otitis media, however, the importance of specific viruses is unclear. In this study molecular methods were used to determine the presence of nucleic acids of human rhinoviruses (HRV; types A, B, and C), respiratory syncytial viruses (RSV; types A and B), bocavirus (HBoV), adenovirus, enterovirus, coronaviruses (229E, HKU1, NL63, and OC43), influenza viruses (types A, B, and C), parainfluenza viruses (types 1, 2, 3, 4A, and 4B), human metapneumovirus, and polyomaviruses (KI and WU) in the nasopharynx of children between 6 and 36 months of age either with (n = 180) or without (n = 66) a history of recurrent acute otitis media and in 238 middle ear effusion samples collected from 143 children with recurrent acute otitis media. The co-detection of these viruses with Streptococcus pneumoniae, nontypeable Haemophilus influenzae, and Moraxella catarrhalis was analyzed. HRV (58.3% vs. 42.4%), HBoV (52.2% vs. 19.7%), polyomaviruses (36.1% vs. 15.2%), parainfluenza viruses (29.4% vs. 9.1%), adenovirus (25.0% vs. 6.1%), and RSV (27.8% vs. 9.1%) were detected significantly more often in the nasopharynx of children with a history of recurrent acute otitis media compared to healthy children. HRV was predominant in the middle ear and detected in middle ear effusion of 46% of children. Since respiratory viruses were detected frequently in the nasopharynx of both children with and without a history of recurrent acute otitis media, the etiological role of specific viruses in recurrent acute otitis media remains uncertain, however, anti-viral therapies may be beneficial in future treatment and prevention strategies for acute otitis media. PMID:21915878

Wiertsema, Selma P; Chidlow, Glenys R; Kirkham, Lea-Ann S; Corscadden, Karli J; Mowe, Eva N; Vijayasekaran, Shyan; Coates, Harvey L; Harnett, Gerald B; Richmond, Peter C

2011-11-01

349

In vitro activity of the tricyclic beta-lactam GV104326.  

PubMed

GV104326 is a novel tricyclic beta-lactam (a trinem or, formerly, tribactam). The in vitro activity of GV104326 was compared with those of cefuroxime, cefixime, amoxicillin, amoxicillin-clavulanic acid, cefpirome, and ciprofloxacin. GV104326 had in vitro activity generally similar to that of cefixime against members of the family Enterobacteriaceae (MIC at which 90% of the isolates are inhibited [MIC90], < or = 2 micrograms/ml), with cefuroxime and amoxicillin-clavulanic acid being 8- to 32-fold less active and with cefpirome being 4- to 8-fold more active against members of this family. The trinem had no activity against Pseudomonas aeruginosa or Stenotrophomonas maltophilia (MIC90, > 128 micrograms/ml) but was the most active agent against Acinetobacter calcoaceticus. GV104326 was particularly active against gram-positive cocci. Ninety percent of methicillin-susceptible Staphylococcus aureus strains were susceptible to 0.03 microgram of GV104326 per ml, making it the most active agent studied. Enterococci and Lancefield group A and B streptococci were generally equally or somewhat more susceptible to GV104326 than they were to amoxicillin. Streptococcus pneumoniae strains were highly susceptible to GV104326, and those strains which showed decreased susceptibility to penicillin were generally twofold more susceptible to the trinem than to amoxicillin. Haemophilus influenzae and Moraxella catarrhalis were highly susceptible to GV104326 (MIC90s, 0.12 and 0.03 microgram/ml, respectively). The anaerobes Clostridium perfringens, Bacteroides fragilis, and Peptostreptococcus spp. were more susceptible to the trinems (formerly tribactams) than to the other agents studied. PMID:8723475

Wise, R; Andrews, J M; Brenwald, N

1996-05-01

350

Results of the Alexander Project: a continuing, multicenter study of the antimicrobial susceptibility of community-acquired lower respiratory tract bacterial pathogens.  

PubMed

In 1992, an ongoing, international multicenter study was established to investigate the antimicrobial susceptibility of community-acquired lower respiratory tract bacterial pathogens: the Alexander Project. Isolates cultured from patients living in geographically separated areas, ten in the European Union (EU) and five in the United States (US), were collected and tested using standard methods in a central laboratory. A total of 4,155 isolates of Haemophilus influenzae was collected during the period 1992-1994. beta-lactamase production was the principal mechanism of resistance observed with overall rates in the US (1992 = 26.3%; 1993 = 28.2%; and 1994 = 30.1%) generally twice those seen in the EU (1992 = 12.3%; 1993 = 14.4%; and 1994 = 15.5%). Chloramphenicol resistance was generally low except in Spanish centers where rates ranging from 4.0 to 15.9% were observed during the study period. One thousand one hundred ninety-three isolates of Moraxella catarrhalis were tested. beta-lactamase production was the only mechanism of resistance of any importance detected, with the vast majority of isolates producing the enzyme. Two thousand eight hundred twenty-nine isolates of Streptococcus pneumoniae were tested. French and Spanish centers provided isolates with the highest rates of either low-level (intermediate) or high-level penicillin resistance, which in 1994 ranged from 10.2 to 31.4% and 30.4 to 40.1% for each resistance category, respectively. With the exception of the fluoroquinolones, rates of resistance to other antimicrobials including the macrolides, doxycycline, chloramphenicol, and trimethoprim/sulfamethoxazole were high, generally, in centers with a high prevalence of penicillin resistance. However, in some centers (Toulouse, France and Genoa, Italy) this association was not complete for the macrolides. PMID:8937841

Grüneberg, R N; Felmingham, D

1996-08-01

351

Antibacterial activities and characterization of novel inhibitors of LpxC.  

PubMed

Lipid A is the hydrophobic anchor of lipopolysaccharide (LPS) and forms the major lipid component of the outer monolayer of the outer membrane of gram-negative bacteria. Lipid A is required for bacterial growth and virulence, and inhibition of its biosynthesis is lethal to bacteria. UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) is a metalloenzyme that catalyzes the second step in the biosynthesis of lipid A. Inhibitors of LpxC have previously been shown to have antibiotic activities. We have screened a metalloenzyme inhibitor library for antibacterial activities against an Escherichia coli strain with reduced LpxC activity. From this screen, a series of sulfonamide derivatives of the alpha-(R)-amino hydroxamic acids, exemplified by BB-78484 and BB-78485, have been identified as having potent inhibitory activities against LpxC in an in vitro assay. Leads from this series showed gram-negative selective activities against members of the Enterobacteriaceae, Serratia marcescens, Morganella morganii, Haemophilus influenzae, Moraxella catarrhalis, and Burkholderia cepacia. BB-78484 was bactericidal against E. coli, achieving 3-log killing in 4 h at a concentration 4 times above the MIC, as would be predicted for an inhibitor of lipid A biosynthesis. E. coli mutants with decreased susceptibility to BB-78484 were selected. Analysis of these mutants revealed that resistance arose as a consequence of mutations in the fabZ or lpxC genes. These data confirm the antibacterial target of BB-78484 and BB-78485 and validate LpxC as a target for gram-negative selective antibacterials. PMID:12019092

Clements, John M; Coignard, Fanny; Johnson, Ian; Chandler, Stephen; Palan, Shilpa; Waller, Andrew; Wijkmans, Jac; Hunter, Michael G

2002-06-01

352

Cefaclor advanced formulation versus cefaclor in the treatment of pneumonia.  

PubMed

The use of cefaclor advanced formulation (cefaclor AF) in the treatment of pneumonia caused by susceptible organisms was investigated in a multi-center trial conducted in the United Kingdom and the United States. A total of 266 patients were enrolled in this double-blind, double-dummy, randomized, parallel study; 132 patients were treated with cefaclor AF and 134 patients received the reference drug cefaclor. Inclusion criteria were a diagnosis of lobar pneumonia or bronchopneumonia, with a positive sputum culture and an infiltrate on chest roentgenogram. Patients received either cefaclor AF (750 mg twice daily) or cefaclor (500 mg three times daily) for 10 to 14 days. Forty patients in the cefaclor AF group and 45 in the cefaclor group were evaluable for efficacy, with 37 (92.5%) and 43 (95.6%), respectively, showing a favorable posttherapy clinical response. Proven or presumed pathogen elimination was achieved in 87.5% and 86.7% of cases, respectively. Both study drugs demonstrated high levels of activity against Streptococcus pneumoniae, Haemophilus influenzae (including beta-lactamase-producing strains), and Moraxella catarrhalis (including beta-lactamase-producing strains). There were no statistically significant differences between drugs in efficacy results. One or more side effects were reported by 42.4% of the patients treated with cefaclor AF and by 44.0% of those treated with cefaclor; diarrhea, nausea, headache, and respiratory disorders were the most common adverse events. No drug-related side effects were seen with a frequency or severity that would be unexpected with the use of oral cephalosporins. Cefaclor AF and cefaclor performed equally well with respect to clinical and bacteriologic response rates in the treatment of pneumonia. PMID:1525791

Casali, L; Voi, M; Janssen, C J; Olovich, K G; Dere, W H

1992-01-01

353

Diagnosis of Tuberculosis by Trained African Giant Pouched Rats and Confounding Impact of Pathogens and Microflora of the Respiratory Tract  

PubMed Central

Trained African giant-pouched rats (Cricetomys gambianus) can detect Mycobacterium tuberculosis and show potential for the diagnosis of tuberculosis (TB). However, rats' ability to discriminate between clinical sputum containing other Mycobacterium spp. and nonmycobacterial species of the respiratory tract is unknown. It is also unknown whether nonmycobacterial species produce odor similar to M. tuberculosis and thereby cause the detection of smear-negative sputum. Sputum samples from 289 subjects were analyzed by smear microscopy, culture, and rats. Mycobacterium spp. were isolated on Lowenstein-Jensen medium, and nonmycobacterial species were isolated on four different media. The odor from nonmycobacterial species from smear- and M. tuberculosis culture-negative sputa detected by ?2 rats (“rat positive”) was analyzed by gas chromatography-mass spectrometry and compared to the M. tuberculosis odor. Rats detected 45 of 56 confirmed cases of TB, 4 of 5 suspected cases of TB, and 63 of 228 TB-negative subjects (sensitivity, 80.4%; specificity, 72.4%; accuracy, 73.9%; positive predictive value, 41.7%; negative predictive value, 93.8%). A total of 37 (78.7%) of 47 mycobacterial isolates were M. tuberculosis complex, with 75.7% from rat-positive sputa. Ten isolates were nontuberculous mycobacteria, one was M. intracellulare, one was M. avium subsp. hominissuis, and eight were unidentified. Rat-positive sputa with Moraxella catarrhalis, Streptococcus pneumoniae, Staphylococcus spp., and Enterococcus spp. were associated with TB. Rhodococcus, Nocardia, Streptomyces, Staphylococcus, and Candida spp. from rat-positive sputa did not produce M. tuberculosis-specific volatiles (methyl nicotinate, methyl para-anisate, and ortho-phenylanisole). Prevalence of Mycobacterium-related Nocardia and Rhodococcus in smear-negative sputa did not equal that of smear-negative mycobacteria (44.7%), of which 28.6% were rat positive. These findings and the absence of M. tuberculosis-specific volatiles in nonmycobacterial species indicate that rats can be trained to specifically detect M. tuberculosis.

Mgode, Georgies F.; Weetjens, Bart J.; Nawrath, Thorben; Cox, Christophe; Jubitana, Maureen; Machang'u, Robert S.; Cohen-Bacrie, Stephan; Bedotto, Marielle; Drancourt, Michel; Schulz, Stefan

2012-01-01

354

Fulminant pertussis: a multi-center study with new insights into the clinico-pathological mechanisms.  

PubMed

Pertussis carries a high risk of mortality in very young infants. The mechanism of refractory cardio-respiratory failure is complex and not clearly delineated. We aimed to examine the clinico-pathological features and suggest how they may be related to outcome, by multi-center review of clinical records and post-mortem findings of 10 patients with fulminant pertussis (FP). All cases were less than 8 weeks of age, and required ventilation for worsening respiratory symptoms and inotropic support for severe hemodynamic compromise. All died or underwent extra corporeal membrane oxygenation (ECMO) within 1 week. All had increased leukocyte counts (from 54 to 132 x 10(9)/L) with prominent neutrophilia in 9/10. The post-mortem demonstrated necrotizing bronchitis and bronchiolitis with extensive areas of necrosis of the alveolar epithelium. Hyaline membranes were present in those cases with viral co-infection. Pulmonary blood vessels were filled with leukocytes without well-organized thrombi. Immunodepletion of the thymus, spleen, and lymph nodes was a common feature. Other organisms were isolated as follows; 2/10 cases Para influenza type 3, 2/10 Moraxella catarrhalis, 1/10 each with respiratory syncytial virus (RSV), a coliform organism, methicillin-resistant Staphylococcus aureus (MRSA), Haemophilus influenzae, Stenotrophomonas maltophilia, methicillin-sensitive Staphylococcus aureus (MSSA), and candida tropicalis. We postulate that severe hypoxemia and intractable cardiac failure may be due to the effects of pertussis toxin, necrotizing bronchiolitis, extensive damage to the alveolar epithelium, tenacious airway secretions, and possibly leukostasis with activation of the immunological cascade, all contributing to increased pulmonary vascular resistance. Cellular apoptosis appeared to underlay much of these changes. The secondary immuno-compromise may facilitate co-infection. PMID:19725100

Sawal, Mohammad; Cohen, Marta; Irazuzta, Jose E; Kumar, Ramani; Kirton, Christine; Brundler, Marie-Anne; Evans, Clair Anne; Wilson, John Andrew; Raffeeq, Parakkal; Azaz, Amer; Rotta, Alexandre T; Vora, Ajay; Vohra, Amit; Abboud, Patricia; Mirkin, L David; Cooper, Mehrengise; Dishop, Megan K; Graf, Jeanine M; Petros, Andy; Klonin, Hilary

2009-10-01

355

Nonantibiotic macrolides prevent human neutrophil elastase-induced mucus stasis and airway surface liquid volume depletion  

PubMed Central

Mucus clearance is an important component of the lung's innate defense system. A failure of this system brought on by mucus dehydration is common to both cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Mucus clearance rates are regulated by the volume of airway surface liquid (ASL) and by ciliary beat frequency (CBF). Chronic treatment with macrolide antibiotics is known to be beneficial to both CF and COPD patients. However, chronic macrolide usage may induce bacterial resistance. We have developed a novel macrolide, 2?-desoxy-9-(S)-erythromycylamine (GS-459755), that has significantly diminished antibiotic activity against Staphylococcus aureus, Streptococcus pneumonia, Moraxella catarrhalis, and Haemophilus influenzae. Since neutrophilia frequently occurs in chronic lung disease and human neutrophil elastase (HNE) induces mucus stasis by activating the epithelial sodium channel (ENaC), we tested the ability of GS-459755 to protect against HNE-induced mucus stasis. GS-459755 had no effect on HNE activity. However, GS-459755 pretreatment protected against HNE-induced ASL volume depletion in human bronchial epithelial cells (HBECs). The effect of GS-459755 on ASL volume was dose dependent (IC50 ?3.9 ?M) and comparable to the antibacterial macrolide azithromycin (IC50 ?2.4 ?M). Macrolides had no significant effect on CBF or on transepithelial water permeability. However, the amiloride-sensitive transepithelial voltage, a marker of ENaC activity, was diminished by macrolide pretreatment. We conclude that GS-459755 may limit HNE-induced activation of ENaC and may be useful for the treatment of mucus dehydration in CF and COPD without inducing bacterial resistance.

Sabater, Juan R.; Clarke, Tainya C.; Tan, Chong D.; Davies, Catrin M.; Liu, Jia; Yeung, Arthur; Garland, Alaina L.; Stutts, M. Jackson; Abraham, William M.; Phillips, Gary; Baker, William R.; Wright, Clifford D.; Wilbert, Sibylle

2013-01-01

356

In vitro activity of the tricyclic beta-lactam GV104326.  

PubMed Central

GV104326 is a novel tricyclic beta-lactam (a trinem or, formerly, tribactam). The in vitro activity of GV104326 was compared with those of cefuroxime, cefixime, amoxicillin, amoxicillin-clavulanic acid, cefpirome, and ciprofloxacin. GV104326 had in vitro activity generally similar to that of cefixime against members of the family Enterobacteriaceae (MIC at which 90% of the isolates are inhibited [MIC90], < or = 2 micrograms/ml), with cefuroxime and amoxicillin-clavulanic acid being 8- to 32-fold less active and with cefpirome being 4- to 8-fold more active against members of this family. The trinem had no activity against Pseudomonas aeruginosa or Stenotrophomonas maltophilia (MIC90, > 128 micrograms/ml) but was the most active agent against Acinetobacter calcoaceticus. GV104326 was particularly active against gram-positive cocci. Ninety percent of methicillin-susceptible Staphylococcus aureus strains were susceptible to 0.03 microgram of GV104326 per ml, making it the most active agent studied. Enterococci and Lancefield group A and B streptococci were generally equally or somewhat more susceptible to GV104326 than they were to amoxicillin. Streptococcus pneumoniae strains were highly susceptible to GV104326, and those strains which showed decreased susceptibility to penicillin were generally twofold more susceptible to the trinem than to amoxicillin. Haemophilus influenzae and Moraxella catarrhalis were highly susceptible to GV104326 (MIC90s, 0.12 and 0.03 microgram/ml, respectively). The anaerobes Clostridium perfringens, Bacteroides fragilis, and Peptostreptococcus spp. were more susceptible to the trinems (formerly tribactams) than to the other agents studied.

Wise, R; Andrews, J M; Brenwald, N

1996-01-01

357

Panel 6: Vaccines  

PubMed Central

Objective To update progress on the effectiveness of vaccine for prevention of acute otitis media (AOM) and identification of promising candidate antigens against Streptococcus pneumoniae, nontypeable Haemophilus influenzae, and Moraxella catarrhalis. Review Methods Literature searches were performed in OvidSP and PubMed restricted to articles published between June 2007 and September 2011. Search terms included otitis media, vaccines, vaccine antigens, and each of the otitis pathogens and candidate antigens identified in the ninth conference report. Conclusions The current report provides further evidence for the effectiveness of pneumococcal conjugate vaccines (PCVs) in the prevention of otitis media. Observational studies demonstrate a greater decline in AOM episodes than reported in clinical efficacy trials. Unmet challenges include extending protection to additional serotypes and additional pathogens, the need to prevent early episodes, the development of correlates of protection for protein antigens, and the need to define where an otitis media vaccine strategy fits with priorities for child health. Implications for Practice Acute otitis media continues to be a burden on children and families, especially those who suffer from frequent recurrences. The 7-valent PCV (PCV7) has reduced the burden of disease as well as shifted the pneumococcal serotypes and the distribution of otopathogens currently reported in children with AOM. Antibiotic resistance remains an ongoing challenge. Multiple candidate antigens have demonstrated the necessary requirements of conservation, surface exposure, immunogenicity, and protection in animal models. Further research on the role of each antigen in pathogenesis, in the development of correlates of protection in animal models, and in new adjuvants to elicit responses in the youngest infants is likely to be productive and permit more antigens to move into human clinical trials.

Pelton, Stephen I.; Pettigrew, Melinda M.; Barenkamp, Stephen J.; Godfroid, Fabrice; Grijalva, Carlos G.; Leach, Amanda; Patel, Janak; Murphy, Timothy F.; Selak, Sanja; Bakaletz, Lauren O.

2014-01-01

358

Efficacy and safety of levofloxacin in patients with bacterial pneumonia evaluated according to the new "Clinical Evaluation Methods for New Antimicrobial Agents to Treat Respiratory Infections (Second Version)".  

PubMed

The guideline for the "Clinical Evaluation Methods for New Antimicrobial Agents to Treat Respiratory Infections (Second Version)," published by the Japanese Society of Chemotherapy in January 2012, was proposed to achieve consistency with FDA guidelines based on the concept of clinical evaluation used in Japan. We assessed the clinical efficacy of levofloxacin (LVFX) in patients with bacterial pneumonia according to this new set of guidelines for the first time. The clinical efficacy of LVFX in patients with community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) at the test of cure (TOC) was 87.5% (56/64) and 85.7% (6/7), respectively, with an overall efficacy of 87.3% (62/71). The clinical efficacy of LVFX at TOC was as follows: intravenous 81.5% (22/27), oral 88.9% (24/27), switchover from intravenous to oral administration 100% (10/10), respectively. The bacterial eradication rate in the patients with CAP and HCAP and overall efficacy at the end of therapy (EOT) was 95.3% (41/43), 100.0% (4/4) and 95.7% (45/47), respectively. The frequent causative bacterial strains included Streptococcus pneumoniae (18), Haemophilus influenzae (14) and Moraxella catarrhalis (6). The incidence of adverse reactions in the patients whose safety was evaluated was 15.7% (14/89), similar to that previously reported. The clinical efficacy of LVFX at the early phase, EOT and TOC of CAP, as assessed according to the new and former guidelines, was 70.4% (38/54) and 27.8% (15/54), 87.0% (60/69) and 79.1% (53/67), 87.5% (56/64) and 88.1% (59/67), respectively, with no significant differences. Therefore, the new efficacy evaluation method can be used in exchange for the former evaluation method. PMID:24787737

Mukae, Hiroshi; Kawanami, Toshinori; Yatera, Kazuhiro; Yanagihara, Katsunori; Yamamoto, Yoshihiro; Kakeya, Hiroshi; Tokimatsu, Issei; Kadota, Junichi; Kohno, Shigeru

2014-07-01

359

Novel Carbapenem Antibiotics for Parenteral and Oral Applications: In Vitro and In Vivo Activities of 2-Aryl Carbapenems and Their Pharmacokinetics in Laboratory Animals  

PubMed Central

SM-295291 and SM-369926 are new parenteral 2-aryl carbapenems with strong activity against major causative pathogens of community-acquired infections such as methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including penicillin-resistant strains), Streptococcus pyogenes, Enterococcus faecalis, Klebsiella pneumoniae, Moraxella catarrhalis, Haemophilus influenzae (including ?-lactamase-negative ampicillin-resistant strains), and Neisseria gonorrhoeae (including ciprofloxacin-resistant strains), with MIC90s of ?1 ?g/ml. Unlike tebipenem (MIC50, 8 ?g/ml), SM-295291 and SM-369926 had no activity against hospital pathogens such as Pseudomonas aeruginosa (MIC50, ?128 ?g/ml). The bactericidal activities of SM-295291 and SM-369926 against penicillin-resistant S. pneumoniae and ?-lactamase-negative ampicillin-resistant H. influenzae were equal or superior to that of tebipenem and greater than that of cefditoren. The therapeutic efficacies of intravenous administrations of SM-295291 and SM-369926 against experimentally induced infections in mice caused by penicillin-resistant S. pneumoniae and ?-lactamase-negative ampicillin-resistant H. influenzae were equal or superior to that of tebipenem and greater than that of cefditoren, respectively, reflecting their in vitro activities. SM-295291 and SM-369926 showed intravenous pharmacokinetics similar to those of meropenem in terms of half-life in monkeys (0.4 h) and were stable against human dehydropeptidase I. SM-368589 and SM-375769, which are medoxomil esters of SM-295291 and SM-369926, respectively, showed good oral bioavailability in rats, dogs, and monkeys (4.2 to 62.3%). Thus, 2-aryl carbapenems are promising candidates that show an ideal broad spectrum for the treatment of community-acquired infections, including infections caused by penicillin-resistant S. pneumoniae and ?-lactamase-negative ampicillin-resistant H. influenzae, have low selective pressure on antipseudomonal carbapenem-resistant nosocomial pathogens, and allow parenteral, oral, and switch therapies.

Fujimoto, Koichi; Hatano, Kazuo; Nakai, Toru; Terashita, Shigeyuki; Matsumoto, Masahiro; Eriguchi, Yoshiro; Eguchi, Ken; Shimizudani, Takeshi; Sato, Kimihiko; Kanazawa, Katsunori; Sunagawa, Makoto; Ueda, Yutaka

2013-01-01

360

Cefpodoxime proxetil in the treatment of lower respiratory tract infections.  

PubMed

Cefpodoxime proxetil is the orally absorbed ester of cefpodoxime, a new third generation cephalosporin. In the gastrointestinal tract, cefpodoxime proxetil is hydrolysed to cefpodoxime, which has potent antibacterial activity against the major bacterial pathogens involved in lower respiratory tract infections: Haemophilus influenzae, Moraxella (Branhamella) catarrhalis (including beta-lactamase-producing strains), and Streptococcus pneumoniae (including amoxicillin-resistant strains). Six randomised comparative studies in patients with lower respiratory tract infections, 5 of which were large (enrollment of more than 200 patients) and double-blind, examined the efficacy and safety of cefpodoxime proxetil. Cefpodoxime proxetil (at a dosage equivalent to 200mg of cefpodoxime) administered twice daily for 5 to 10 days was similar in clinical and bacteriological efficacy to the following: amoxicillin 500mg 3 times daily in the treatment of community-acquired pneumonia; intramuscular ceftriaxone Ig once daily in the treatment of pulmonary infections in hospitalised patients; and to amoxicillin/clavulanic acid 500/125mg 3 times daily in the treatment of acute exacerbations of chronic bronchitis (AECB). Additionally, a dosage equivalent to 100mg or 200mg of cefpodoxime twice daily was similar in clinical and bacteriological efficacy to amoxicillin 250mg 3 times daily in the treatment of bronchitis (acute or AECB). The adverse events noted with cefpodoxime proxetil administration were similar to those associated with other beta-lactam antibacterials and most commonly involved the gastrointestinal tract and skin or mucous membranes. Thus, cefpodoxime proxetil is a useful addition to the antibacterials available for the treatment of infections of the lower respiratory tract. PMID:1726206

Geddes, A M

1991-01-01

361

In Vitro and In Vivo Antimicrobial Activities of T-3811ME, a Novel Des-F(6)-Quinolone  

PubMed Central

The in vitro and in vivo activities of T-3811ME, a novel des-F(6)-quinolone, were evaluated in comparison with those of some fluoroquinolones, including a newly developed one, trovafloxacin. T-3811, a free base of T-3811ME, showed a wide range of antimicrobial spectra, including activities against Chlamydia trachomatis, Mycoplasma pneumoniae, and Mycobacterium tuberculosis. In particular, T-3811 exhibited potent activity against various gram-positive cocci, with MICs at which 90% of the isolates are inhibited (MIC90s) of 0.025 to 6.25 ?g/ml. T-3811 was the most active agent against methicillin-resistant Staphylococcus aureus and streptococci, including penicillin-resistant Streptococcus pneumoniae (PRSP). T-3811 also showed potent activity against quinolone-resistant gram-positive cocci with GyrA and ParC (GrlA) mutations. The activity of T-3811 against members of the family Enterobacteriaceae and nonfermentative gram-negative rods was comparable to that of trovafloxacin. In common with other fluoroquinolones, T-3811 was highly active against Haemophilus influenzae, Moraxella catarrhalis, and Legionella sp., with MIC90s of 0.0125 to 0.1 ?g/ml. T-3811 showed a potent activity against anaerobic bacteria, such as Bacteroides fragilis and Clostridium difficile. T-3811 was the most active agent against C. trachomatis (MIC, 0.008 ?g/ml) and M. pneumoniae (MIC90, 0.0313 ?g/ml). The activity of T-3811 against M. tuberculosis (MIC90, 0.0625 ?g/ml) was potent and superior to that of trovafloxacin. In experimental systemic infection with a GrlA mutant of S. aureus and experimental pneumonia with PRSP in mice, T-3811ME showed excellent therapeutic efficacy in oral and subcutaneous administrations.

Takahata, Masahiro; Mitsuyama, Junichi; Yamashiro, Yoshiko; Yonezawa, Minoru; Araki, Harumi; Todo, Yozo; Minami, Shinzaburo; Watanabe, Yasuo; Narita, Hirokazu

1999-01-01

362

Structures of Staphylococcus aureus peptide deformylase in complex with two classes of new inhibitors.  

PubMed

Peptide deformylase (PDF) catalyzes the removal of the formyl group from the N-terminal methionine residue in newly synthesized polypeptides, which is an essential process in bacteria. Four new inhibitors of PDF that belong to two different classes, hydroxamate/pseudopeptide compounds [PMT387 (7a) and PMT497] and reverse-hydroxamate/nonpeptide compounds [PMT1039 (15e) and PMT1067], have been developed. These compounds inhibited the growth of several pathogens involved in respiratory-tract infections, such as Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae, and leading nosocomial pathogens such as Staphylococcus aureus and Klebsiella pneumoniae with a minimum inhibitory concentration (MIC) in the range 0.1-0.8?mg?ml(-1). Interestingly, the reverse-hydroxamate/nonpeptide compounds showed a 250-fold higher antimicrobial activity towards S. aureus, although the four compounds showed similar K(i) values against S. aureus PDF enzymes, with K(i) values in the 11-85?nM range. To provide a structural basis for the discovery of additional PDF inhibitors, the crystal structures of S. aureus PDF in complex with the four inhibitors were determined at resolutions of 1.90-2.30?Å. The inhibitor-bound structures displayed distinct deviations depending on the inhibitor class. The distance between the Zn(2+) ion and the carbonyl O atom of the hydroxamate inhibitors (or the hydroxyl O atom of the reverse-hydroxamate inhibitors) appears to be correlated to S. aureus inhibition activity. The structural information reported in this study should aid in the discovery of new PDF inhibitors that can be used as novel antibacterial drugs. PMID:22751663

Lee, Sang Jae; Lee, Seung-Jae; Lee, Seung Kyu; Yoon, Hye-Jin; Lee, Hyung Ho; Kim, Kyeong Kyu; Lee, Bong Jin; Lee, Byung Il; Suh, Se Won

2012-07-01

363

Association between Ocular Bacterial Carriage and Follicular Trachoma Following Mass Azithromycin Distribution in The Gambia  

PubMed Central

Background Trachoma, caused by ocular Chlamydia trachomatis infection, is the leading infectious cause of blindess, but its prevalence is now falling in many countries. As the prevalence falls, an increasing proportion of individuals with clinical signs of follicular trachoma (TF) is not infected with C. trachomatis. A recent study in Tanzania suggested that other bacteria may play a role in the persistence of these clinical signs. Methodology/Principal Findings We examined associations between clinical signs of TF and ocular colonization with four pathogens commonly found in the nasopharnyx, three years after the initiation of mass azithromycin distribution. Children aged 0 to 5 years were randomly selected from 16 Gambian communitites. Both eyes of each child were examined and graded for trachoma according to the World Health Organization (WHO) simplified system. Two swabs were taken from the right eye: one swab was processed for polymerase chain reaction (PCR) using the Amplicor test for detection of C. trachomatis DNA and the second swab was processed by routine bacteriology to assay for the presence of viable Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and Moraxella catarrhalis. Prevalence of TF was 6.2% (96/1538) while prevalence of ocular C. trachomatis infection was 1.0% (16/1538). After adjustment, increased odds of TF were observed in the presence of C. trachomatis (OR?=?10.4, 95%CI 1.32–81.2, p?=?0.03), S. pneumoniae (OR?=?2.14, 95%CI 1.03–4.44, p?=?0.04) and H. influenzae (OR?=?4.72, 95% CI 1.53–14.5, p?=?0.01). Conclusions/Significance Clinical signs of TF can persist in communities even when ocular C. trachomatis infection has been controlled through mass azithromycin distribution. In these settings, TF may be associated with ocular colonization with bacteria commonly carried in the nasopharnyx. This may affect the interpretation of impact surveys and the determinations of thresholds for discontinuing mass drug administration.

Burr, Sarah E.; Hart, John D.; Edwards, Tansy; Baldeh, Ignatius; Bojang, Ebrima; Harding-Esch, Emma M.; Holland, Martin J.; Lietman, Thomas M.; West, Sheila K.; Mabey, David C. W.; Sillah, Ansumana; Bailey, Robin L.

2013-01-01

364

Haemophilus influenzae type b as an important cause of culture-positive acute otitis media in young children in Thailand: a tympanocentesis-based, multi-center, cross-sectional study  

PubMed Central

Background Streptococcus pneumoniae (S. pneumoniae) and Haemophilus influenzae (H. influenzae) are considered major causes of bacterial acute otitis media (AOM) worldwide, but data from Asia on primary causes of AOM are limited. This tympanocentesis-based, multi-center, cross-sectional study assessed bacterial etiology and antimicrobial susceptibility of AOM in Thailand. Methods Children 3 to 59 months presenting with AOM (Moraxella catarrhalis (6% (7/118)) or Streptococcus pyogenes (3% (4/118)). The most common pneumococcal serotypes were 19F (26%) and 14 (22%). The majority of H. influenzae isolates were encapsulated (18/21), with 13 type b (Hib) representing 62% of all H. influenzae isolate or 11% of all samples (13/118), and there were only 3 non-typeable isolates. Despite high antibiotic resistance, amoxicillin/clavulanate susceptibility was high. No pneumococcal vaccine use was reported. Conclusions S. pneumoniae and H. influenzae, both frequently antibiotic resistant, were leading causes of bacterial AOM and there was an unexpectedly high burden of Hib in this population unvaccinated by any Hib conjugate vaccine. Conjugate vaccines effective against pneumococcus and H. influenzae could potentially reduce the burden of AOM in this population.

2014-01-01

365

Potentially Pathogenic Airway Bacteria and Neutrophilic Inflammation in Treatment Resistant Severe Asthma  

PubMed Central

Background Molecular microbiological analysis of airway samples in asthma has demonstrated an altered microbiome in comparison to healthy controls. Such changes may have relevance to treatment-resistant severe asthma, particularly those with neutrophilic airway inflammation, as bacteria might be anticipated to activate the innate immune response, a process that is poorly steroid responsive. An understanding of the relationship between airway bacterial presence and dominance in severe asthma may help direct alternative treatment approaches. Objective We aimed to use a culture independent analysis strategy to describe the presence, dominance and abundance of bacterial taxa in induced sputum from treatment resistant severe asthmatics and correlate findings with clinical characteristics and airway inflammatory markers. Methods Induced sputum was obtained from 28 stable treatment-resistant severe asthmatics. The samples were divided for supernatant IL-8 measurement, cytospin preparation for differential cell count and Terminal Restriction Fragment Length Polymorphism (T-RFLP) profiling for bacterial community analysis. Results In 17/28 patients, the dominant species within the airway bacterial community was Moraxella catarrhalis or a member of the Haemophilus or Streptococcus genera. Colonisation with these species was associated with longer asthma disease duration (mean (SD) 31.8 years (16.7) vs 15.6 years (8.0), p?=?0.008), worse post-bronchodilator percent predicted FEV1 (68.0% (24.0) vs 85.5% (19.7), p?=?0.025) and higher sputum neutrophil differential cell counts (median (IQR) 80% (67–83) vs 43% (29–67), p?=?0.001). Total abundance of these organisms significantly and positively correlated with sputum IL-8 concentration and neutrophil count. Conclusions Airway colonisation with potentially pathogenic micro-organisms in asthma is associated with more severe airways obstruction and neutrophilic airway inflammation. This altered colonisation may have a role in the development of an asthma phenotype that responds less well to current asthma therapies.

Grainge, Christopher; Rogers, Geraint B.; Kehagia, Valia; Lau, Laurie; Carroll, Mary P.; Bruce, Kenneth D.; Howarth, Peter H.

2014-01-01

366

Novel Bacterial NAD+-Dependent DNA Ligase Inhibitors with Broad-Spectrum Activity and Antibacterial Efficacy In Vivo? †  

PubMed Central

DNA ligases are indispensable enzymes playing a critical role in DNA replication, recombination, and repair in all living organisms. Bacterial NAD+-dependent DNA ligase (LigA) was evaluated for its potential as a broad-spectrum antibacterial target. A novel class of substituted adenosine analogs was discovered by target-based high-throughput screening (HTS), and these compounds were optimized to render them more effective and selective inhibitors of LigA. The adenosine analogs inhibited the LigA activities of Escherichia coli, Haemophilus influenzae, Mycoplasma pneumoniae, Streptococcus pneumoniae, and Staphylococcus aureus, with inhibitory activities in the nanomolar range. They were selective for bacterial NAD+-dependent DNA ligases, showing no inhibitory activity against ATP-dependent human DNA ligase 1 or bacteriophage T4 ligase. Enzyme kinetic measurements demonstrated that the compounds bind competitively with NAD+. X-ray crystallography demonstrated that the adenosine analogs bind in the AMP-binding pocket of the LigA adenylation domain. Antibacterial activity was observed against pathogenic Gram-positive and atypical bacteria, such as S. aureus, S. pneumoniae, Streptococcus pyogenes, and M. pneumoniae, as well as against Gram-negative pathogens, such as H. influenzae and Moraxella catarrhalis. The mode of action was verified using recombinant strains with altered LigA expression, an Okazaki fragment accumulation assay, and the isolation of resistant strains with ligA mutations. In vivo efficacy was demonstrated in a murine S. aureus thigh infection model and a murine S. pneumoniae lung infection model. Treatment with the adenosine analogs reduced the bacterial burden (expressed in CFU) in the corresponding infected organ tissue as much as 1,000-fold, thus validating LigA as a target for antibacterial therapy.

Mills, Scott D.; Eakin, Ann E.; Buurman, Ed T.; Newman, Joseph V.; Gao, Ning; Huynh, Hoan; Johnson, Kenneth D.; Lahiri, Sushmita; Shapiro, Adam B.; Walkup, Grant K.; Yang, Wei; Stokes, Suzanne S.

2011-01-01

367

Influence of Various Polymorphic Variants of Cytochrome P450 Oxidoreductase (POR) on Drug Metabolic Activity of CYP3A4 and CYP2B6  

PubMed Central

Cytochrome P450 oxidoreductase (POR) is known as the sole electron donor in the metabolism of drugs by cytochrome P450 (CYP) enzymes in human. However, little is known about the effect of polymorphic variants of POR on drug metabolic activities of CYP3A4 and CYP2B6. In order to better understand the mechanism of the activity of CYPs affected by polymorphic variants of POR, six full-length mutants of POR (e.g., Y181D, A287P, K49N, A115V, S244C and G413S) were designed and then co-expressed with CYP3A4 and CYP2B6 in the baculovirus-Sf9 insect cells to determine their kinetic parameters. Surprisingly, both mutants, Y181D and A287P in POR completely inhibited the CYP3A4 activity with testosterone, while the catalytic activity of CYP2B6 with bupropion was reduced to approximately ?70% of wild-type activity by Y181D and A287P mutations. In addition, the mutant K49N of POR increased the CLint (Vmax/Km) of CYP3A4 up to more than 31% of wild-type, while it reduced the catalytic efficiency of CYP2B6 to 74% of wild-type. Moreover, CLint values of CYP3A4-POR (A115V, G413S) were increased up to 36% and 65% of wild-type respectively. However, there were no appreciable effects observed by the remaining two mutants of POR (i.e., A115V and G413S) on activities of CYP2B6. In conclusion, the extent to which the catalytic activities of CYP were altered did not only depend on the specific POR mutations but also on the isoforms of different CYP redox partners. Thereby, we proposed that the POR-mutant patients should be carefully monitored for the activity of CYP3A4 and CYP2B6 on the prescribed medication.

Naranmandura, Hua; Zeng, Su; Chen, Shu Qing

2012-01-01

368

[Investigation of bacterial etiology with conventional and multiplex PCR methods in adult patients with community-acquired pneumonia].  

PubMed

Community-acquired pneumonia (CAP) is still a serious life-threatening disease, in which the etiologic agent cannot be identified in more than 50% of patients despite advanced diagnostic methods. The most commonly used methods in the determination of CAP etiology are culture and serological tests. Since early and accurate therapy reduces the mortality in CAP cases, rapid and reliable diagnostic methods are needed. The aim of this study was to determine the bacterial etiology in adult patients with CAP by implementing multiplex polymerase chain reaction/reverse line blot hybridization (M-PCR/RLBH) assay combined with conventional methods. A total of 128 cases (94 were male; age range: 19-81 years, mean age: 58) who were admitted to our hospital and clinically diagnosed as CAP between November 2008 - November 2010, were included in the study. Respiratory samples (sputum and/or bronchoalveolar lavage) obtained from patients were searched by M-PCR/RLBH method (Gen ID®, Autoimmun Diagnostika GmbH, Germany) in terms of the presence of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella pneumophila nucleic acids. The samples were simultaneously inoculated onto 5% sheep blood agar, chocolate agar, haemophilus isolation agar, buffered charcoal yeast extract-selective agar and EMB agar media for cultivation. Serum samples obtained from the cases were tested for IgM and IgG antibodies against C.pneumoniae by microimmunofluorescence (Focus Diagnostic, USA) and against L.pneumophila and M.pneumoniae by indirect immunofluorescence (Euroimmun, Germany) methods. The bacterial etiology was identified in 59 (46.1%) of 128 patients with CAP and a total of 73 pathogens were detected. The leading organism was S.pneumoniae (n= 32, 25%), followed by H.influenzae and M.pneumoniae (n= 9, 7%), gram-negative bacilli (n= 10, 7.8%), M.catarrhalis (n= 6, 4.7%), C.pneumoniae (n= 4, 3.2%), L.pneumophila (n= 2, 1.6%) and Staphylococcus aureus (n= 1, 1.4%). Infection with atypical pathogens were detected in 15 (11.7%), and mixed infections in 14 (10.9%) patients. The detection rate of microorganisms (S.pneumoniae, H.influenzae, M.catarrhalis, C.pneumoniae, L.pneumophilia, M.pneumoniae) searched by M-PCR/RLBH method was 41.4% (53/128), while those microorganisms were detected in 23.4% (30/128) of the patients by conventional methods, representing a significant difference (p< 0.05). It was concluded that M-PCR/RLBH method supplemented the determination of bacterial etiology in CAP cases by increasing the rate of detection from 23.4% to 41.4%. The results indicated that empirical treatment of CAP should primarily include antibiotics against S.pneumoniae, M.pneumoniae and H.influenzae in our region. PMID:23188566

Kurutepe, Semra; Ecemi?, Talat; Ozgen, Aylin; Biçmen, Can; Celik, P?nar; Akto?u Özkan, Serir; Sürücüo?lu, Süheyla

2012-10-01

369

SIMULTANEOUS DEGRADATION OF ORGANOPHOSPHORUS PESTICIDES AND P-NITROPHENOL BY A GENETICALLY ENGINEERED MORAXELLA SP. WITH SURFACE-EXPRESSED ORGANOPHOSPHORUS HYDROLASE. (R827227)  

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

370

AMPEROMETRIC MICROBIAL BIOSENSOR FOR DIRECT DETERMINATION OF ORGANOPHOSPHATE NERVE AGENTS USING RECOMBINANT MORAXELLA SP. WITH SURFACE EXPRESSED ORGANOPHOSPHORUS HYDROLASE. (R828160)  

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

371

Estudio teórico de la desorción de Na y K de SiO2 estimulada por la acción de fotones o electrones  

NASA Astrophysics Data System (ADS)

Se ha estudiado el mecanismo de generación de sodio y potasio atómico a partir de muestras de SiO2 utilizando cálculos basados tanto en la teoría del funcional de la densidad como en métodos post-Hartree Fock, así como en el método de cluster para modelar el sólido. Como consecuencia del estudio se han propuesto distintos caminos posibles para la desorción, estimulada por la acción de fotones o electrones, de sodio y potasio desde el óxido de silicio, proporcionando por lo tanto una explicación a la atmósfera tenue de sodio y potasio de La Luna.

Domínguez Ariza, D.; López, N.; Illas, F.; Pacchioni, G.; Madey, T. E.

372

Vasculitis retiniana por VIH  

Microsoft Academic Search

Case reportWe present a case of a 47 year-old woman, infected with human immunodeficiency virus (HIV) diagnosed 5 years ago without receiving any treatment, who had floaters in her left eye. A peripheral retinal vasculitis was discovered and confirmed by an angiography. No source of infection was found, antiretroviral and corticosteroid treatment was given, with a complete resolution of the

P. Drake-Casanova; J. Paz Moreno-Arrones; M. Gorroño Echebarría; I. Dapena-Sevilla; J. Pareja-Esteban; E. Vleming-Pinilla

2010-01-01

373

Double-locus sequence typing using porA and peb1A for epidemiological studies of Campylobacter jejuni.  

PubMed

Campylobacter jejuni is the leading cause of foodborne bacterial gastroenteritis worldwide. Bacterial typing schemes play an important role in epidemiological investigations to trace the source and route of transmission of the infectious agent by identifying outbreak and differentiating among sporadic infections. In this study, a double-locus sequence typing (DLST) scheme for C. jejuni based on concatenated partial sequences of porA and peb1A genes is proposed. The DLST scheme was validated using 50 clinical and environmental C. jejuni strains isolated from human (C5, H, H15-H19), chicken (CH1-CH15), water (W2-W17), and ovine samples (OV1-OV6). The scheme was found to be highly discriminatory (discrimination index [DI]=0.964) and epidemiologically concordant based on C. jejuni strains studied. The DLST showed discriminatory power above 0.95 and excellent congruence to multilocus sequence typing and can be recommended as a rapid and low-cost typing scheme for epidemiological investigation of C. jejuni. It is suggested that the DLST scheme is suitable for identification of outbreak strains and differentiation of the sporadic infection strains. PMID:24404778

Ahmed, Monir U; Dunn, Louise; Valcanis, Mary; Hogg, Geoff; Ivanova, Elena P

2014-03-01

374

Timectomia estendida por cirurgia torácica videoassistida e cervicotomia no tratamento da miastenia * Extended thymectomy through video assisted thoracic surgery and cervicotomy in the treatment of myasthenia  

Microsoft Academic Search

Introdução: A relação entre a miastenia e o timo é evidente e o tratamento atual desta condição inclui a timectomia. No entanto, uma revisão de nossa experiência com a timectomia revelou a necessidade do uso de uma técnica mais radical. Objetivo: Analisar retrospectivamente pacientes portado- res de miastenia gravis que foram submetidos a timectomia radical por videotoracoscopia, ressaltando vantagens do

EDUARDO HARUO SAITO; GÉRSON C. MAGALHÃES; LUIZ CARLOS; AGUIAR VAZ; VICENTE FARIA CERVANTE

2003-01-01

375

Nuevo sitio web en español del Instituto Nacional del Cáncer, (NCI, por sus siglas en inglés) Cancer.gov en español - Silvia Inéz Salazar - transcript  

Cancer.gov

Transmisiones de radio para promover Cancer.gov en espa%XF1ol | Nuevo sitio web en espa%XF1ol del Instituto Nacional del C%XE1ncer, (NCI, por sus siglas en ingl%XE9s) Cancer.gov en espa%XF1ol | Transcripci%XF3n Transmisiones de radio para promover

376

Modelos teóricos que nos ayudan a comprender el gobierno de las sociedades cooperativas, una apuesta por el enfoque de los stakeholders  

Microsoft Academic Search

En la actualidad, el entorno competitivo es cada vez más incierto y complejo. Las características de los mercados actuales hacen que sea cada vez más difícil conseguir una ventaja competitiva sostenible en el tiempo para la empresa, por lo que hay que innovar en formas de gestión y de gobierno para ser competitivo. De esta manera, se está produciendo un

Cristina Pedrosa Ortega

2009-01-01

377

GERENCIAMENTO POR PROCESSO: UM ESTUDO DE CASO NO SETOR SUCROALCOOLEIRO BRASILEIRO PROCESS MANAGEMENT: A CASE STUDY OF THE BRAZILIAN SUGAR ALCOHOL SECTOR  

Microsoft Academic Search

Resumo: O objetivo deste trabalho é analisar os resultados da mudança na estrutura funcional de uma empresa sucroalcooleira, realizada por uma empresa de consultoria especializada em gestão empresarial. Assim, para a realização deste trabalho foi usado o método de estudo de caso único, baseado em relatórios de consultoria. Os principais resultados encontrados foram: (1) o retorno financeiro devido à mudança

Ricardo Alexandre Feliciano; Roberto Gilioli Rotondaro

378

El proceso hacia la integracion de la equidad por genero al curriculo.(The Process of the Integration of Gender Equity in the Curriculum.)  

ERIC Educational Resources Information Center

"El Proyecto Colaborativo de Equidad por Genero en la Educacion," or the Collaborative Project for Gender Equity in Education, was undertaken in Puerto Rico between 1990 and 1992 to study how to facilitate the integration of gender equity themes in the curriculum through the direct action of participating teachers. A study examined the attitudes…

Rivera-Bermudez, Carmen D.

379

Corynebacterium jeikeium jk0268 Constitutes for the 40 Amino Acid Long PorACj, Which Forms a Homooligomeric and Anion-Selective Cell Wall Channel  

PubMed Central

Corynebacterium jeikeium, a resident of human skin, is often associated with multidrug resistant nosocomial infections in immunodepressed patients. C. jeikeium K411 belongs to mycolic acid-containing actinomycetes, the mycolata and contains a channel-forming protein as judged from reconstitution experiments with artificial lipid bilayer experiments. The channel-forming protein was present in detergent treated cell walls and in extracts of whole cells using organic solvents. A gene coding for a 40 amino acid long polypeptide possibly responsible for the pore-forming activity was identified in the known genome of C. jeikeium by its similar chromosomal localization to known porH and porA genes of other Corynebacterium strains. The gene jk0268 was expressed in a porin deficient Corynebacterium glutamicum strain. For purification temporarily histidine-tailed or with a GST-tag at the N-terminus, the homogeneous protein caused channel-forming activity with an average conductance of 1.25 nS in 1M KCl identical to the channels formed by the detergent extracts. Zero-current membrane potential measurements of the voltage dependent channel implied selectivity for anions. This preference is according to single-channel analysis caused by some excess of cationic charges located in the channel lumen formed by oligomeric alpha-helical wheels. The channel has a suggested diameter of 1.4 nm as judged from the permeability of different sized hydrated anions using the Renkin correction factor. Surprisingly, the genome of C. jeikeium contained only one gene coding for a cell wall channel of the PorA/PorH type found in other Corynebacterium species. The possible evolutionary relationship between the heterooligomeric channels formed by certain Corynebacterium strains and the homooligomeric pore of C. jeikeium is discussed.

Norouzy, Amir; Schulz, Robert; Nau, Werner M.; Kleinekathofer, Ulrich; Tauch, Andreas; Benz, Roland

2013-01-01

380

ALTERAÇÃO POPULACIONAL DE CÉLULAS NA CAMADA INTRAEPITELIAL E ALTERAÇÕES MORFOLÓGICAS DA PAREDE INTESTINAL CAUSADA PELA INFECÇÃO POR Toxocara vitulorum EM BEZERROS BÚFALOS (Bubalus Bubalis)  

Microsoft Academic Search

NEVES, M.F.; STARKE-BUZETTI, W.A. (Populational alteration of cells in the intestinal intraepithelial layer and morphological changes of the intestinal wall elicited by Toxocara vitulorum infection in buffalo calves (Bubalus bubalis)). Alteração populacional de células na camada intraepitelial e alterações morfológicas da parede intestinal causada pela infecção por Toxocara vitulorum em bezerros búfalos (Bubalus Bubalis). Revista Brasileira de Parasitologia Veterinária, v.

MARIA FRANCISCA NEVES; WILMA A. STARKE-BUZETTI

2005-01-01

381

Neisseria meningitidis PorB, a Toll-Like Receptor 2 Ligand, Improves the Capacity of Francisella tularensis Lipopolysaccharide To Protect Mice against Experimental Tularemia  

Microsoft Academic Search

Francisella tularensis causes severe pneumonia that can be fatal if it is left untreated. Due to its potential use as a biological weapon, research is being conducted to develop an effective vaccine and to select and study adjuvant molecules able to generate a better and long-lasting protective effect. PorB, a porin from Neisseria meningitidis, is a well-established Toll-like receptor 2

Damiana Chiavolini; Susan Weir; John R. Murphy; Lee M. Wetzler

2008-01-01

382

Los índices de mortalidad por cáncer de pulmón siguen bajando y contribuyen a reducción de índices generales de muertes por cáncer; Informe Anual a la Nación tiene una sección especial de los efectos de otras enfermedades en la supervivencia de pacientes  

Cancer.gov

El Informe Anual a la Nación sobre el Estado del Cáncer (1975 a 2010), mostró un descenso más acelerado que en años anteriores de los índices de mortalidad por cáncer de pulmón. También contiene una sección especial que destaca los efectos significativos que tienen otras enfermedades en la supervivencia de pacientes con cáncer.

383

El Informe Anual a la Nación indica que las tasas de mortalidad por cáncer continúan declinando. Se observan tasas menores de cáncer en las poblaciones latinas de los Estados Unidos.  

Cancer.gov

Un informe nuevo de las principales organizaciones oncológicas de la nación informa que el riesgo de los estadounidenses de morir por cáncer continúa descendiendo, y que mantiene una tendencia que comenzó a principios de los años noventa. Preguntas y respuestas

384

Population pharmacokinetics and pharmacodynamics of garenoxacin in patients with community-acquired respiratory tract infections.  

PubMed

Garenoxacin (T-3811ME, BMS-284756) is a novel, broad-spectrum des-F(6) quinolone currently under study for the treatment of community-acquired respiratory tract infections. This analysis assessed garenoxacin population pharmacokinetics and exposure-response relationships for safety (adverse effects [AE]) and antimicrobial activity (clinical cure and bacteriologic eradication of Streptococcus pneumoniae and the grouping of Haemophilus influenzae, Haemophilus parainfluenzae, and Moraxella catarrhalis). Data were obtained from three phase II clinical trials of garenoxacin administered orally as 400 mg once daily for 5 to 10 days for the treatment of community-acquired pneumonia, acute exacerbation of chronic bronchitis, and sinusitis. Samples were taken from each patient before drug administration, 2 h following administration of the first dose, and on the day 3 to 5 visit. Individual Bayesian estimates of the fu (fraction unbound), the Cmax, and the fu for the area under the concentration-time curve from 0 to 24 h (fu AUC(0-24)) were calculated as measurements of drug exposure by using an ex vivo assessment of average protein binding. Regression analysis was performed to examine the following relationships: treatment-emergent AE incidence and AUC(0-24), Cmax, or patient factors; clinical response or bacterial eradication and drug exposure (fu Cmax/MIC, fu AUC(0-24)/MIC, and other exposure covariates); or disease and patient factors. Garenoxacin pharmacokinetics were described by a one-compartment model with first-order absorption and elimination. Clearance was dependent on creatinine clearance, ideal body weight, age, obesity, and concomitant use of pseudoephedrine. The volume of distribution was dependent on weight and gender. Patients with mild or moderate renal dysfunction had, on average, approximately a 16 or 26% decrease in clearance, respectively, compared to patients of the same gender and obesity classification with normal renal function. AE occurrence was not related to garenoxacin exposure. Overall, clinical cure and bacterial eradication rates were 91 and 90%, respectively, for S. pneumoniae and 93 and 92%, respectively, for the grouping of H. influenzae, H. parainfluenzae, and M. catarrhalis. The fu AUC(0-24)/MIC ratios were high (>90% were >200), and none of the pharmacokinetic-pharmacodynamic exposure measurements indexed to the MIC or other factors were significant predictors of clinical or bacteriologic response. Garenoxacin clearance was primarily related to creatinine clearance and ideal body weight. Although garenoxacin exposure was approximately 25% higher for patients with moderate renal dysfunction, this increase does not appear to be clinically significant as exposures in this patient population were not significant predictors of AE occurrence. Garenoxacin exposures were at the upper end of the exposure-response curves for measurements of antimicrobial activity, suggesting that 400 mg of garenoxacin once daily is a safe and adequate dose for the treatment of the specified community-acquired respiratory tract infections. PMID:15561855

Van Wart, Scott; Phillips, Luann; Ludwig, Elizabeth A; Russo, Rene; Gajjar, Diptee A; Bello, Akintunde; Ambrose, Paul G; Costanzo, Christopher; Grasela, Thaddeus H; Echols, Roger; Grasela, Dennis M

2004-12-01

385

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2006)].  

PubMed

From October 2006 to September 2007, we collected the specimen from 356 patients with lower respiratory tract infections in 14 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 414 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in infection, 407 strains were examined. The isolated bacteria were: Staphylococcus aureus 64, Streptococcus pneumoniae 96, Haemophilus influenzae 87, Pseudomonas aeruginosa (non-mucoid) 52, P. aeruginosa (mucoid) 11, Klebsiella pneumoniae 20, and Moraxella catarrhalis 44. Of 64 S. aureus strains, those with 2 microg/ml or less of MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4 microg/ml or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 27 (42.2%) and 37 (57.8%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all strains at 0.063 microg/ml or less. Against MRSA, vancomycin and linezolid showed the most potent activity and inhibited the growth of all the strains at 1 microg/ml. Carbapenems showed the most potent activities against S. pneumoniae and in particular, panipenem inhibited the growth of all the strains at 0.063 microg/ml or less. Imipenem and faropenem also had a preferable activity and inhibited the growth of all the strains at 0.125 and 0.5 microg/ml, respectively. In contrast, there were high-resistant strains (MIC: over 128 microg/ml) for erythromycin (45.8%) and clindamycin (20.8%). Against H. influenzae, levofloxacin showed the most potent activity and its MIC90 was 0.063 microg/ml or less. Meropenem showed the most potent activity against P. aeruginosa (mucoid) and its MIC90 was 0.5 microg/ml. Against P. aeruginosa (non-mucoid), tobramycin had the most potent activity and its MIC90 was 2 microg/ml. Against K. pneumoniae, cefozopran was the most potent activity and inhibited the growth of all the strains at 0.063 microg/ml or less. Also, all the antibacterial agents except ampicillin generally showed a potent activity against M. catarrhalis and the MIC90 of them were 2 microg/ml or less. The approximately half the number (50.6%) of the patients with respiratory infection were aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 49.2% and 28.1% of all the respiratory infections, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. pneumoniae (29.2%), S. aureus (20.8%), and H. influenzae (12.9%). H. influenzae (25.0%) and P. aeruginosa (21.7%) also were frequently isolated from the patients with chronic bronchitis. Before the antibacterial agent administration, the bacteria frequently isolated from the patients were S. pneumoniae (27.5%) and H. influenzae (22.5%). The bacteria frequently isolated from the patients treated with macrolides was P. aeruginosa, and its isolation frequently was 39.4%. PMID:24649798

Goto, Hajime; Takeda, Hideki; Kawai, Shin; Suwabe, Akira; Watanabe, Suguru; Okazaki, Mitsuhiro; Ashino, Yugo; Shimada, Kaoru; Aoki, Nobuki; Sato, Tetsuo; Honma, Yasuo; Mori, Takeshi; Kudo, Kouichiro; Sugiyama, Haruhito; Kondo, Shigemi; Tanaka, Tsukasa; Kido, Kenji; Yoshimura, Kunihiko; Oguri, Toyoko; Yamamoto, Makoto; Nakamori, Yoshitaka; Inoue, Hiroshi; Yamauchi, Kohei; Sumitomo, Midori; Endo, Shigeatsu; Nakadate, Toshihide; Oka, Mikio; Kobashi, Yoshihiro; Saita, Naoki; Yanagihara, Katsunori; Kondou, Akira; Matsuda, Junichi; Nakano, Michiko; Kohno, Shigeru; Oikawa, Satoru

2013-12-01

386

Variation in P450 oxidoreductase (POR) A503V and flavin-containing monooxygenase (FMO)-3 E158K is associated with minor alterations in nicotine metabolism, but does not alter cigarette consumption.  

PubMed

The rates of nicotine metabolism differ widely, even after controlling for genetic variation in the major nicotine-metabolizing enzyme, CYP2A6. Genetic variants in an additional nicotine-metabolizing enzyme, flavin-containing monooxygenase (FMO)-3, and an obligate microsomal CYP-supportive enzyme, cytochrome P450 oxidoreductase (POR), were investigated. We examined the impact of FMO3 E158K and POR A503V before and after stratifying by CYP2A6 metabolism group. In 130 nonsmokers of African descent who received 4 mg oral nicotine, FMO3 158K trended toward slower nicotine metabolism in reduced CYP2A6 metabolizers (P=0.07) only, whereas POR 503V was associated with faster CYP2A6 activity (nicotine metabolite ratio) in normal (P=0.03), but not reduced, CYP2A6 metabolizers. Neither FMO3 158K nor POR 503V significantly altered the nicotine metabolic ratio (N=659), cigarette consumption (N=667), or urine total nicotine equivalents (N=418) in smokers of African descent. Thus, FMO3 E158K and POR A503V are minor sources of nicotine metabolism variation, insufficient to appreciably alter smoking. PMID:24448396

Chenoweth, Meghan J; Zhu, Andy Z X; Sanderson Cox, Lisa; Ahluwalia, Jasjit S; Benowitz, Neal L; Tyndale, Rachel F

2014-03-01

387

Antimicrobial activity of the pleuromutilin antibiotic BC-3781 against bacterial pathogens isolated in the SENTRY antimicrobial surveillance program in 2010.  

PubMed

BC-3781 is a novel semisynthetic pleuromutilin antibiotic inhibiting bacterial protein synthesis. BC-3781 has completed a phase 2 clinical trial in acute bacterial skin and skin structure infections (ABSSSI). Its antibacterial spectrum additionally covers the predominant pathogens causing community-acquired bacterial pneumonia (CABP). In this study, the antibacterial activity of BC-3781 was evaluated against a contemporary collection of 10,035 bacterial isolates predominately causing ABSSSI and CABP, among other infections, collected within the SENTRY Antimicrobial Surveillance Program worldwide in 2010. BC-3781 exhibited potent activity against organisms commonly isolated from ABSSSI such as Staphylococcus aureus (MIC50/90, 0.12/0.12 ?g/ml; 99.8% inhibited at ?0.5 ?g/ml), beta-hemolytic streptococci (MIC50/90, 0.03/0.03 ?g/ml; 99.3% inhibited at ?0.5 ?g/ml), and coagulase-negative staphylococci (CoNS; MIC50/90, 0.06/0.12 ?g/ml; 97.8% inhibited at ?1 ?g/ml). BC-3781 displayed similar MIC distributions among methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) S. aureus strains. BC-3781 was also active against Enterococcus faecium, with 76.3% of vancomycin-susceptible and 97.0% of vancomycin-resistant isolates being inhibited at BC-3781 concentrations of ?1 ?g/ml. Beta-hemolytic and viridans group streptococci were highly susceptible to BC-3781, with 99.3% and 96.7% of isolates inhibited at ?0.5 ?g/ml, respectively. Further, activity of BC-3781 against Streptococcus pneumoniae (MIC50/90, 0.12/0.25 ?g/ml), Haemophilus influenzae (MIC50/90, 1/2 ?g/ml), and Moraxella catarrhalis (MIC50/90, 0.12/0.25 ?g/ml) was not negatively influenced by ?-lactamase production or resistance to other antimicrobial classes tested. In all, BC-3781 displayed a very potent antibacterial profile including the most prevalent bacterial pathogens causing ABSSSI and CABP, thus warranting further clinical development of this antibiotic in these and possibly other indications. PMID:23836172

Paukner, Susanne; Sader, Helio S; Ivezic-Schoenfeld, Zrinka; Jones, Ronald N

2013-09-01

388

Diagnosis of atypical pathogens in patients hospitalized with community-acquired respiratory infection.  

PubMed

The object of our study was to determine the proportion of atypical respiratory pathogens among patients hospitalized with a community-acquired respiratory infection. From September 1997 to May 1999, 159 patients (57% male, median age 55, range 1-88 y) admitted to 3 regional hospitals for a community acquired respiratory infection, were enrolled in the study. Microbiological diagnosis for the atypical pathogens Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila was performed with PCR on a throat swab, sputum and/or broncho alveolar lavage (BAL). In addition, Legionella species other than L. pneumophila (L. non-pneumophila species) were detected by PCR. Two serum samples were collected and processed for M. pneumoniae and C. pneumoniae serology. In total, 27 patients (17%) were diagnosed with an atypical pathogen. Infection with M. pneumoniae was detected in 19 patients (12%) (PCR positive n = 7), with C. pneumoniae in 5 patients (3%) (PCR positive n = 0) and with L. pneumophila in 4 patients (2.5%) (PCR positive n = 4). In 54 (34%) patients routine microbiological investigations revealed aetiological agents other than the 3 atypical pathogens, the most frequently diagnosed pathogens being Streptococcus pneumoniae (n = 18), Haemophilus influenzae (n = 17), Gram-negative rods (n = 13), Moraxella catarrhalis (n = 6) and Staphylococcus aureus (n = 6). More than 1 pathogen was found in 13 patients. Atypical pathogens were found more often in the young age group (0-18 y), in contrast to bacterial pathogens that were found more often in the older age groups (> or = 65 y). Atypical pathogens were found less often in patients with a clinical presentation of atypical pneumonia. Legionella species other than L. pneumophila were found by PCR in 13 patients (8%), and in 6 patients in combination with another pathogen. An atypical pathogen (M. pneumoniae, C. pneumoniae or L. pneumophila) was found in 17% of the patients hospitalized with a community acquired respiratory infection, predominantly in the young age group. The role of Legionella non-pneumophila species as pathogen in community acquired respiratory infection needs to be determined. The clinical presentation does not predict the type of pathogen found. PMID:15198183

Schneeberger, Peter M; Dorigo-Zetsma, J Wendeline; van der Zee, Anneke; van Bon, Marion; van Opstal, Jean-Louis

2004-01-01

389

In vitro activity of tigecycline (GAR-936) tested against 11,859 recent clinical isolates associated with community-acquired respiratory tract and gram-positive cutaneous infections.  

PubMed

Tigecycline is a novel 9-t-butylglycylamido derivative of minocycline that has demonstrated activity against a variety of bacterial pathogens, including resistant isolates, during preclinical studies. In vitro activities of tigecycline and comparators were tested against 11,859 recent (2000 and 2002) bacterial strains recovered from patients in 29 countries with community-acquired respiratory tract disease (3,317 gram-positive and -negative strains) and skin and soft tissue infections (8,542 gram-positive strains). All oxacillin-susceptible and -resistant Staphylococcus aureus (5,077 strains; tigecycline MIC(90), 0.5 microg/mL) and coagulase-negative staphylococci (1,432 strains; MIC(90), 0.5 microg/mL), penicillin-susceptible and -resistant Streptococcus pneumoniae (1,585 strains; MIC(90), < or =0.25 microg/mL), viridans group streptococci (212 strains; MIC(90), < or =0.25-0.5 microg/mL), vancomycin-susceptible and -resistant enterococci (1,416 strains; MIC(90), 0.25-0.5 microg/mL), beta-haemolytic streptococci (405 strains; MIC(90), < or =0.25 microg/mL), beta-lactamase positive and negative Haemophilus influenzae (1,220 strains; MIC(90), 1 microg/mL), Moraxella catarrhalis (495 strains; MIC(90), 0.25 microg/mL), and Neisseria meningitidis (17 strains; MIC(90), < or =0.12 microg/mL) were inhibited by 2 microg/mL or less of tigecycline. Whereas potency of tetracycline and doxycycline markedly dropped in various resistant organism subsets, tigecycline was unaffected with an overall MIC(90) of 0.5 microg/mL. These findings confirm that tigecycline maintains a truly broad spectrum like the tetracycline class while enhancing potency. It also incorporates stability to the commonly occurring tetracycline resistance mechanisms, making it an attractive candidate for continued clinical development against pathogens causing serious community-acquired respiratory tract infections, as well as cutaneous infections. PMID:15246511

Fritsche, Thomas R; Kirby, Jeffrey T; Jones, Ronald N

2004-07-01

390

Antibacterial activity of 41 antimicrobials tested against over 2773 bacterial isolates from hospitalized patients with pneumonia: I--results from the SENTRY Antimicrobial Surveillance Program (North America, 1998).  

PubMed

Pneumonia is the second most frequent cause of nosocomial infection, and hospitalization frequently is needed for community-acquired pneumonia. Knowledge of causative pathogens through periodic surveillance, and their prevailing antimicrobial susceptibility patterns becomes paramount in choosing appropriate empiric therapy. The SENTRY Antimicrobial Surveillance Program, tracks pathogen distribution worldwide since 1997 and documents emerging resistance to a wide range of antimicrobial agents. During the respiratory disease season in 1998, each of 30 medical centers (25 in the United States [US], and five in Canada [CAN]) contributed 100 consecutive isolates obtained from hospitalized patients with suspected pneumonia. The 2773 organisms, processed by the monitor consisted of a total of 35 species, with Staphylococcus aureus comprising 25.6% of all isolates and five other species (Pseudomonas aeruginosa 18.7%, Haemophilus influenzae 9.4%, Streptococcus pneumoniae 7.8%, Klebsiella spp. 7.0%, and Enterobacter spp. 6.7%) making up almost 50% of the total. In the US, pneumococci (8.5%) were more prevalent than in CAN (4.1%; p = 0.001). The US isolates of S. pneumoniae were variably susceptible to penicillin (76.8%), with non-susceptible strains demonstrating greater levels of cross resistance to macrolides (31.8%), cefepime (9.0%) and cefotaxime (6.8%), but remaining susceptible to gatifloxacin and quinupristin/dalfopristin. H. influenzae and Moraxella catarrhalis were generally ampicillin-resistant, 40.4-44.4% and 93.7-95.7%, respectively. P. aeruginosa remained very susceptible to amikacin (91.3-93.8%) > tobramycin > meropenem > piperacillin/tazobactam > gentamicin > piperacillin > cefepime (80.0-81.8%). Extended spectrum beta-lactamase phenotypes among the Klebsiella spp. were isolated from five medical centers in the US and were 4.8-6.0% overall; a rate similar to the previous year. Among the US isolates of Enterobacter spp., only 77.6% and 79.6% were susceptible to ceftazidime and cefotaxime, respectively, but >90% were inhibited by cefepime, imipenem, meropenem, aminoglycosides, and fluoroquinolones. Isolates from CAN were generally more susceptible, except for Pseudomonas isolates, where resistance to aminoglycosides, fluoroquinolones and imipenem was greater. The SENTRY Program results outline important national differences in the frequencies of pathogen occurrence, but more importantly, identify unstable patterns of resistance to available antimicrobial drugs, and serves as a reference for results of other local, national or international investigations. PMID:11248523

Mathai, D; Lewis, M T; Kugler, K C; Pfaller, M A; Jones, R N

2001-02-01

391

The incidence and aetiology of hospitalised community-acquired pneumonia among Vietnamese adults: a prospective surveillance in Central Vietnam  

PubMed Central

Background Lower respiratory tract infection (LRTI) including Community-acquired pneumonia (CAP) is a common infectious disease that is associated with significant morbidity and mortality. The patterns of aetiological pathogens differ by region and country. Special attention must be paid to CAP in Southeast Asia (SEA), a region facing rapid demographic transition. Estimates burden and aetiological patterns of CAP are essential for the clinical and public health management. The purposes of the study are to determine the incidence, aetiological pathogens, clinical pictures and risk factors of community-acquired pneumonia (CAP) in the Vietnamese adult population. Methods A prospective surveillance for hospitalised adult CAP was conducted in Khanh Hoa Province, Central Vietnam. All adults aged ?15 years with lower respiratory tract infections (LRTI) admitted to a provincial hospital from September 2009 to August 2010 were enrolled in the study. Patients were classified into CAP and non-pneumonic LRTI (NPLRTI) according to the radiological findings. Bacterial pathogens were identified from sputum samples by the conventional culture and polymerase chain reaction (PCR) for Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis; 13 respiratory viruses were identified from nasopharyngeal specimens by PCR. Results Of all 367 LRTI episodes examined, 174 (47%) were CAP. Older age, the presence of underlying respiratory conditions, and higher index score of smoking were associated with CAP. The one-year estimated incidence of hospitalised adult CAP in our study population was 0.81 per 1,000 person years. The incidence increased considerably with age and was highest among the elderly. The case fatality proportion of hospitalised CAP patients was 9.8%. Among 286 sputum samples tested for bacterial PCR, 79 (28%) were positive for H. influenzae, and 65 (23%) were positive for S. pneumoniae. Among 357 samples tested for viral PCR, 73 (21%) were positive for respiratory viruses; influenza A (n?=?32, 9%) was the most common. Conclusions The current adult CAP incidence in Vietnam was relatively low; this result was mainly attributed to the young age of our study population.

2013-01-01

392

Association between early bacterial carriage and otitis media in Aboriginal and non-Aboriginal children in a semi-arid area of Western Australia: a cohort study  

PubMed Central

Background Streptococcus pneumoniae (Pnc), nontypeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) are the most important bacterial pathogens associated with otitis media (OM). Previous studies have suggested that early upper respiratory tract (URT) bacterial carriage may increase risk of subsequent OM. We investigated associations between early onset of URT bacterial carriage and subsequent diagnosis of OM in Aboriginal and non-Aboriginal children living in the Kalgoorlie-Boulder region located in a semi-arid zone of Western Australia. Methods Aboriginal and non-Aboriginal children who had nasopharyngeal aspirates collected at age 1-?

2012-01-01

393

Guide to selection of fluoroquinolones in patients with lower respiratory tract infections.  

PubMed

Newer fluoroquinolones such as levofloxacin, moxifloxacin, gatifloxacin and gemifloxacin have several attributes that make them excellent choices for the therapy of lower respiratory tract infections. In particular, they have excellent intrinsic activity against Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and the atypical respiratory pathogens. Fluoroquinolones may be used as monotherapy to treat high-risk patients with acute exacerbation of chronic bronchitis, and for patients with community-acquired pneumonia requiring hospitalisation, but not admission to intensive care. Overall, the newer fluoroquinolones often achieve clinical cure rates in > or =90% of these patients. However, rates may be lower in hospital-acquired pneumonia, and this infection should be treated on the basis of anticipated organisms and evaluation of risk factors for specific pathogens such as Pseudomonas aeruginosa. In this setting, an antipseudomonal fluoroquinolone may be used in combination with an antipseudomonalbeta-lactam. Concerns are now being raised about the widespread use, and possibly misuse, of fluoroquinolones and the emergence of resistance among S. pneumoniae, Enterobacteriaceae and P. aeruginosa. A number of pharmacokinetic parameters such as the peak concentration of the antibacterial after a dose (C(max)), and the 24-hour area under the concentration-time curve (AUC24) and their relationship to pharmacodynamic parameters such as the minimum inhibitory and the mutant prevention concentrations (MIC and MPC, respectively) have been proposed to predict the effect of fluoroquinolones on bacterial killing and the emergence of resistance. Higher C(max)/MIC or AUC24/MIC and C(max)/MPC or AUC24/MPC ratios, either as a result of dose administration or the susceptibility of the organism, may lead to a better clinical outcome and decrease the emergence of resistance, respectively. Pharmacokinetic profiles that are optimised to target low-level resistant minor subpopulations of bacteria that often exist in infections may help preserve fluoroquinolones as a class. To this end, optimising the AUC24/MPC or C(max)/MPC ratios is important, particularly against S. pneumoniae, in the setting of lower respiratory tract infections. Agents such as moxifloxacin and gemifloxacin with high ratios against this organism are preferred, and agents such as ciprofloxacin with low ratios should be avoided. For agents such as levofloxacin and gatifloxacin, with intermediate ratios against S. pneumoniae, it may be worthwhile considering alternative dose administration strategies, such as using higher dosages, to eradicate low-level resistant variants. This must, of course, be balanced against the potential of toxicity. Innovative approaches to the use of fluoroquinolones are worth testing in further in vitro experiments as well as in clinical trials. PMID:15892589

Shams, Wael E; Evans, Martin E

2005-01-01

394

In vitro activity of BAY 12-8039, a new fluoroquinolone.  

PubMed

The in vitro activity of BAY 12-8039, a new fluoroquinolone, was studied in comparison with those of ciprofloxacin, trovafloxacin (CP 99,219), cefpodoxime, and amoxicillin-clavulanate against gram-negative, gram-positive, and anaerobic bacteria. Its activity against mycobacteria and chlamydia was also investigated. BAY 12-8039 was active against members of the family Enterobacteriaceae (MIC at which 90% of strains tested were inhibited [MIC90S] < or = 1 microgram/ml, except for Serratia spp. MIC90 2 microgram/ml), Neisseria spp. (MIC90S, 0.015 microgram/ml), Haemophilus influenzae (MIC90, 0.03 microgram/ml), and Moraxella catarrhalis (MIC90, 0.12 micrgram/ml), and these results were comparable to those obtained for ciprofloxacin and trovafloxacin. Against Pseudomonas aeruginosa, the quinolones were more active than the beta-lactam agents but BAY 12-8039 was less active than ciprofloxacin. Strains of Stenotrophomonas maltophilia were fourfold more susceptible to BAY 12-8039 and trovafloxacin (MIC90S, 2 micrograms/ml) than to ciprofloxacin. BAY 12-8039 was as active as trovafloxacin but more active than ciprofloxacin against Streptococcus pneumoniae (MIC90, 0.25 microgram/ml) and methicillin-susceptible Staphylococcus auerus (MIC90S, 0.12 micrograms/ml). The activity of BAY 12-8039 against meth