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Sample records for albicans candida spp

  1. Detection of Salmonella spp., Candida albicans, Aspergillus spp., and Antimicrobial Residues in Raw and Processed Cow Milk from Selected Smallholder Farms of Zimbabwe

    PubMed Central

    Mhone, Tryness Anastazia; Matope, Gift; Saidi, Petronella Tapiwa

    2012-01-01

    A cross-sectional study was conducted to detect the presence of Salmonella spp., Candida albicans, Aspergillus spp., and antimicrobial residues in raw milk (n = 120) and processed cow milk (n = 20) from smallholder dairy farms from three sites in Zimbabwe. Culture and isolation of Salmonella spp., C. albicans, and Aspergillus spp. were performed using selective media, while antimicrobial residues were detected by a dye reduction test. No Salmonella, but C. albicans (17.5%; 21/120), Aspergillus spp. (0.8%; 1/120), and antimicrobial residues (2.5%; 3/120) were detected from raw milk. C. albicans was isolated from all three sites, while Aspergillus spp. and antimicrobial residues were detected from sites 1 and 3, respectively. From processed milk, only C. albicans (5%) was isolated while Aspergillus spp. and antimicrobial residues were not detected. These results suggested low prevalence of Salmonella spp. and Aspergillus spp. and a relatively high prevalence of C. albicans in raw milk from the smallholder farms. The potential public health risks of C. albicans and the detected antimicrobial residues need to be considered. Thus, educating farmers on improving milking hygiene and storage of milk and establishing programmes for monitoring antimicrobial residues may help to improve the safety of milk from smallholder farms. PMID:23050199

  2. Disinfection efficacy of chlorine and peracetic acid alone or in combination against Aspergillus spp. and Candida albicans in drinking water.

    PubMed

    Sisti, Maurizio; Brandi, Giorgio; De Santi, Mauro; Rinaldi, Laura; Schiavano, Giuditta F

    2012-03-01

    The aim of the present study was to evaluate the fungicidal activity of chlorine and peracetic acid in drinking water against various pathogenic Aspergillus spp. and Candida albicans strains. A. nidulans exhibited the greatest resistance, requiring 10 ppm of chlorine for 30 min contact time for a complete inactivation. Under the same experimental conditions, peracetic acid was even less fungicidal. In this case, A. niger proved to be the most resistant species (50 ppm for 60 min for complete inactivation). All Aspergillus spp. were insensitive to 10 ppm even with extended exposure (>5 h). The combination of chlorine and peracetic acid against Aspergillus spp. did not show synergistic effects except in the case of A. flavus. Complete growth inhibition of C. albicans was observed after about 3 h contact time with 0.2 ppm. C. albicans was less sensitive to peracetic acid. Hence the concentrations of chlorine that are usually present in drinking water distribution systems are ineffective against several Aspergillus spp. and peracetic acid cannot be considered an alternative to chlorine for disinfecting drinking water. The combination of the two biocides is not very effective in eliminating filamentous fungi at the concentrations permitted for drinking water disinfection.

  3. Candida albicans commensalism in the gastrointestinal tract.

    PubMed

    Neville, B Anne; d'Enfert, Christophe; Bougnoux, Marie-Elisabeth

    2015-11-01

    Candida albicans is a polymorphic yeast species that often forms part of the commensal gastrointestinal mycobiota of healthy humans. It is also an important opportunistic pathogen. A tripartite interaction involving C. albicans, the resident microbiota and host immunity maintains C. albicans in its commensal form. The influence of each of these factors on C. albicans carriage is considered herein, with particular focus on the mycobiota and the approaches used to study it, models of gastrointestinal colonization by C. albicans, the C. albicans genes and phenotypes that are necessary for commensalism and the host factors that influence C. albicans carriage.

  4. Urinary tract infections and Candida albicans

    PubMed Central

    Behzadi, Payam; Behzadi, Elham

    2015-01-01

    Introduction Urinary tract candidiasis is known as the most frequent nosocomial fungal infection worldwide. Candida albicans is the most common cause of nosocomial fungal urinary tract infections; however, a rapid change in the distribution of Candida species is undergoing. Simultaneously, the increase of urinary tract candidiasis has led to the appearance of antifungal resistant Candida species. In this review, we have an in depth look into Candida albicans uropathogenesis and distribution of the three most frequent Candida species contributing to urinary tract candidiasis in different countries around the world. Material and methods For writing this review, Google Scholar –a scholarly search engine– (http://scholar.google.com/) and PubMed database (http://www.ncbi.nlm.nih.gov/pubmed/) were used. The most recently published original articles and reviews of literature relating to the first three Candida species causing urinary tract infections in different countries and the pathogenicity of Candida albicans were selected and studied. Results Although some studies show rapid changes in the uropathogenesis of Candida species causing urinary tract infections in some countries, Candida albicans is still the most important cause of candidal urinary tract infections. Conclusions Despite the ranking of Candida albicans as the dominant species for urinary tract candidiasis, specific changes have occurred in some countries. At this time, it is important to continue the surveillance related to Candida species causing urinary tract infections to prevent, control and treat urinary tract candidiasis in future. PMID:25914847

  5. [Hypersensitivity pneumonitis after exposure to Candida spp].

    PubMed

    Serrano, Carlos; Torrego, Alfonso; Loosli, Alfonso; Valero, Antonio; Picado, César

    2010-05-01

    Hypersensitivity pneumonitis (HP) is a lung disease caused by heavy and recurrent inhalation of antigens. We describe the case of a patient with HP caused by domestic exposure to Candida spp. The diagnosis was made by taking into consideration the, clinical presentation, exposure history, radiological findings, bronchoalveolar lavage, lung function and the immuno-allergy study. The diagnosis was definitively confirmed by performing a specific bronchial provocation test. It has been shown that there is cross-reactivity between different Candida species, and despite making the diagnosis in this case with Candida albicans, we were unable to define exactly which species was responsible for the HP.

  6. In vitro modification of Candida albicans invasiveness.

    PubMed

    Fontenla de Petrino, S E; de Jorrat, M E; Sirena, A; Valdez, J C; Mesón, O

    1986-05-01

    Candida albicans produces germ-tubes (GT) when it is incubated in animal or human serum. This dimorphism is responsible for its invasive ability. The purpose of the present paper is (1) to evaluate the ability of rat peritoneal macrophages to inhibit GT production of ingested Candida albicans, obtained from immunized rats and then activated in vitro with Candida-induced lymphokines; (2) to determinate any possible alteration of phagocytic and candidacidal activities. The phagocytes were obtained from rats immunized with viable C. albicans. Some of them were exposed to Candida-induced lymphokines in order to activate the macrophages in vitro. The monolayers of activated, immune and normal macrophages were infected with a C. albicans suspension during 4 hr. Activated macrophages presented not only the highest phagocytic and candidacidal activities but a noticeable inhibition of GT formation and incremented candidacidal activity.

  7. In vitro modification of Candida albicans invasiveness.

    PubMed

    Fontenla de Petrino, S E; de Jorrat, M E; Sirena, A; Valdez, J C; Mesón, O

    1986-05-01

    Candida albicans produces germ-tubes (GT) when it is incubated in animal or human serum. This dimorphism is responsible for its invasive ability. The purpose of the present paper is (1) to evaluate the ability of rat peritoneal macrophages to inhibit GT production of ingested Candida albicans, obtained from immunized rats and then activated in vitro with Candida-induced lymphokines; (2) to determinate any possible alteration of phagocytic and candidacidal activities. The phagocytes were obtained from rats immunized with viable C. albicans. Some of them were exposed to Candida-induced lymphokines in order to activate the macrophages in vitro. The monolayers of activated, immune and normal macrophages were infected with a C. albicans suspension during 4 hr. Activated macrophages presented not only the highest phagocytic and candidacidal activities but a noticeable inhibition of GT formation and incremented candidacidal activity. PMID:3523254

  8. GENETIC CONTROL OF CANDIDA ALBICANS BIOFILM DEVELOPMENT

    PubMed Central

    Finkel, Jonathan S.; Mitchell, Aaron P.

    2014-01-01

    Preface Candida species cause frequent infections due to their ability to form biofilms – surface-associated microbial communities – primarily on implanted medical devices. Increasingly, mechanistic studies have identified the gene products that participate directly in Candida albicans biofilm formation, as well as the regulatory circuitry and networks that control their expression and activity. These studies have revealed new mechanisms and signals that govern C. albicans biofilm formation and associated drug resistance, thus providing biological insight and therapeutic foresight. PMID:21189476

  9. Beyond Candida albicans: Mechanisms of immunity to non-albicans Candida species.

    PubMed

    Whibley, Natasha; Gaffen, Sarah L

    2015-11-01

    The fungal genus Candida encompasses numerous species that inhabit a variety of hosts, either as commensal microbes and/or pathogens. Candida species are a major cause of fungal infections, yet to date there are no vaccines against Candida or indeed any other fungal pathogen. Our knowledge of immunity to Candida mainly comes from studies on Candida albicans, the most frequent species associated with disease. However, non-albicans Candida (NAC) species also cause disease and their prevalence is increasing. Although research into immunity to NAC species is still at an early stage, it is becoming apparent that immunity to C. albicans differs in important ways from non-albicans species, with important implications for treatment, therapy and predicted demographic susceptibility. This review will discuss the current understanding of immunity to NAC species in the context of immunity to C. albicans, and highlight as-yet unanswered questions.

  10. Candida/Candida biofilms. First description of dual-species Candida albicans/C. rugosa biofilm.

    PubMed

    Martins, Carlos Henrique Gomes; Pires, Regina Helena; Cunha, Aline Oliveira; Pereira, Cristiane Aparecida Martins; Singulani, Junya de Lacorte; Abrão, Fariza; Moraes, Thais de; Mendes-Giannini, Maria José Soares

    2016-04-01

    Denture liners have physical properties that favour plaque accumulation and colonization by Candida species, irritating oral tissues and causing denture stomatitis. To isolate and determine the incidence of oral Candida species in dental prostheses, oral swabs were collected from the dental prostheses of 66 patients. All the strains were screened for their ability to form biofilms; both monospecies and dual-species combinations were tested. Candida albicans (63 %) was the most frequently isolated microorganism; Candida tropicalis (14 %), Candida glabrata (13 %), Candida rugosa (5 %), Candida parapsilosis (3 %), and Candida krusei (2 %) were also detected. The XTT assay showed that C. albicans SC5314 possessed a biofilm-forming ability significantly higher (p < 0.001) than non-albicans Candida strains, after 6 h 37 °C. The total C. albicans CFU from a dual-species biofilm was less than the total CFU of a monospecies C. albicans biofilm. In contrast to the profuse hyphae verified in monospecies C. albicans biofilms, micrographies showed that the C. albicans/non-albicans Candida biofilms consisted of sparse yeast forms and profuse budding yeast cells that generated a network. These results suggested that C. albicans and the tested Candida species could co-exist in biofilms displaying apparent antagonism. The study provide the first description of C. albicans/C. rugosa mixed biofilm.

  11. Neutrophil activation by Candida glabrata but not Candida albicans promotes fungal uptake by monocytes.

    PubMed

    Duggan, Seána; Essig, Fabian; Hünniger, Kerstin; Mokhtari, Zeinab; Bauer, Laura; Lehnert, Teresa; Brandes, Susanne; Häder, Antje; Jacobsen, Ilse D; Martin, Ronny; Figge, Marc Thilo; Kurzai, Oliver

    2015-09-01

    Candida albicans and Candida glabrata account for the majority of candidiasis cases worldwide. Although both species are in the same genus, they differ in key virulence attributes. Within this work, live cell imaging was used to examine the dynamics of neutrophil activation after confrontation with either C. albicans or C. glabrata. Analyses revealed higher phagocytosis rates of C. albicans than C. glabrata that resulted in stronger PMN (polymorphonuclear cells) activation by C. albicans. Furthermore, we observed differences in the secretion of chemokines, indicating chemotactic differences in PMN signalling towards recruitment of further immune cells upon confrontation with Candida spp. Supernatants from co-incubations of neutrophils with C. glabrata primarily attracted monocytes and increased the phagocytosis of C. glabrata by monocytes. In contrast, PMN activation by C. albicans resulted in recruitment of more neutrophils. Two complex infection models confirmed distinct targeting of immune cell populations by the two Candida spp.: In a human whole blood infection model, C. glabrata was more effectively taken up by monocytes than C. albicans and histopathological analyses of murine model infections confirmed primarily monocytic infiltrates in C. glabrata kidney infection in contrast to PMN-dominated infiltrates in C. albicans infection. Taken together, our data demonstrate that the human opportunistic fungi C. albicans and C. glabrata are differentially recognized by neutrophils and one outcome of this differential recognition is the preferential uptake of C. glabrata by monocytes.

  12. Short peptides allowing preferential detection of Candida albicans hyphae.

    PubMed

    Kaba, Hani E J; Pölderl, Antonia; Bilitewski, Ursula

    2015-09-01

    Whereas the detection of pathogens via recognition of surface structures by specific antibodies and various types of antibody mimics is frequently described, the applicability of short linear peptides as sensor molecules or diagnostic tools is less well-known. We selected peptides which were previously reported to bind to recombinant S. cerevisiae cells, expressing members of the C. albicans Agglutinin-Like-Sequence (ALS) cell wall protein family. We slightly modified amino acid sequences to evaluate peptide sequence properties influencing binding to C. albicans cells. Among the selected peptides, decamer peptides with an "AP"-N-terminus were superior to shorter peptides. The new decamer peptide FBP4 stained viable C. albicans cells more efficiently in their mature hyphal form than in their yeast form. Moreover, it allowed distinction of C. albicans from other related Candida spp. and could thus be the basis for the development of a useful tool for the diagnosis of invasive candidiasis.

  13. Adaptive immune responses to Candida albicans infection.

    PubMed

    Richardson, Jonathan P; Moyes, David L

    2015-01-01

    Fungal infections are becoming increasingly prevalent in the human population and contribute to morbidity and mortality in healthy and immunocompromised individuals respectively. Candida albicans is the most commonly encountered fungal pathogen of humans, and is frequently found on the mucosal surfaces of the body. Host defense against C. albicans is dependent upon a finely tuned implementation of innate and adaptive immune responses, enabling the host to neutralise the invading fungus. Central to this protection are the adaptive Th1 and Th17 cellular responses, which are considered paramount to successful immune defense against C. albicans infections, and enable tissue homeostasis to be maintained in the presence of colonising fungi. This review will highlight the recent advances in our understanding of adaptive immunity to Candida albicans infections.

  14. Development of DNA probes for Candida albicans

    SciTech Connect

    Cheung, L.L.; Hudson, J.B.

    1988-07-01

    An attempt was made to produce DNA probes that could be used as a rapid and efficient means of detecting candidiasis (invasive Candida infection) in immunocompromised patients. Whole DNA from Candida albicans was digested with restriction endonuclease, and the resulting fragments were randomly cloned into a plasmid vector. Several recombinant plasmids were evaluated for cross-hybridization to various other Candida species, other fungal DNAs, and to nonfungal DNAs. Cross reactions were observed between the probes and different yeasts, but none with unrelated DNAs. Some recombinants were genus-specific, and two of these were applied to the analysis of C. albicans growth curves. It became evident that, although both /sup 32/P- and biotin-labelled probes could be made quite sensitive, a possible limitation in their diagnostic potential was the poor liberation of Candida DNA from cells. Thus, better methods of treatment of clinical specimens will be required before such probes will be useful in routine diagnosis.

  15. Association of KPC-producing Klebsiella pneumoniae colonization or infection with Candida isolation and selection of non-albicans species.

    PubMed

    Papadimitriou-Olivgeris, Matthaios; Spiliopoulou, Anastasia; Fligou, Fotini; Manolopoulou, Patroula; Spiliopoulou, Iris; Vrettos, Theofanis; Dodou, Vasiliki; Filos, Kriton S; Anastassiou, Evangelos D; Marangos, Markos; Christofidou, Myrto

    2014-11-01

    Clinical specimens from 565 patients hospitalized in 2 intensive care units (ICUs A and B) during a 28-month period were cultured on appropriate media for isolation of Candida. Forty-nine (9%) patients had at least a Candida spp.-positive sample. Candida albicans was the predominant species isolated from 26 (53%) patients. Seventeen patients (3%) developed candidemia. Multivariate analysis showed that obesity, female gender, hospitalization during summer months, admission at ICU B, parenteral nutrition, administration of metronidazole, transplantation, and KPC-producing Klebsiella pneumoniae (KPC-Kp) infection were independently associated with Candida spp. isolation. Candidemia was associated with cortisone administration, KPC-Kp infection, and presence of colostomy or abdominal catheter. Administration of fluconazole was a protective factor for both Candida spp. isolation and infection, leading to selection of Candida non-albicans species. Among several risk factors, KPC-Kp infection and colonization are identified as statistically significant factors associated with Candida isolation, especially of non-albicans species.

  16. Candida albicans isolates from a Malaysian hospital exhibit more potent phospholipase and haemolysin activities than non-albicans Candida isolates.

    PubMed

    Chin, V K; Foong, K J; Maha, A; Rusliza, B; Norhafizah, M; Ng, K P; Chong, P P

    2013-12-01

    This study was aimed at determining the phospholipase and haemolysin activity of Candida isolates in Malaysia. A total of 37 Candida clinical isolates representing seven species, Candida albicans (12), Candida tropicalis (8), Candida glabrata (4), Candida parapsilosis (1), Candida krusei (4), Candida orthopsilosis (1) and Candida rugosa (7) were tested. In vitro phospholipase activity was determined by using egg yolk plate assay whereas in vitro haemolysin activity was tested by using blood plate assay on sheep blood Sabouraud's dextrose agar (SDA) enriched with glucose. Phospholipase activity was detected in 75% (9 out of 12) of the C. albicans isolates. Among the 25 non- C. albicans Candida isolates, phospholipase activity was detected in only 24% of these isolates. The phospholipase activity of C. albicans was significantly higher than that of the non- C. albicans Candida isolates (P=0.002). Haemolysin activity was detected in 100% of the C. albicans, C. tropicalis, C. glabrata, C. krusei, C. parapsilosis, and C. orthopsilosis isolates while 75% of the C. krusei isolates and 12.3% of the C. rugosa isolates showed haemolysin activity. The haemolytic activity of C. albicans was significantly higher than that of the non- C. albicans Candida isolates (P=0.0001).The findings in this study indicate that C. albicans isolates in Malaysia may possess greater virulence potential than the non-albicans species.

  17. Milestones in Candida albicans Gene Manipulation

    PubMed Central

    Samaranayake, Dhanushki P.; Hanes, Steven D.

    2011-01-01

    In the United States, candidemia is one of the most common hospital-acquired infections and is estimated to cause 10,000 deaths per year. The species Candida albicans is responsible for the majority of these cases. As C. albicans is capable of developing resistance against the currently available drugs, understanding the molecular basis of drug resistance, finding new cellular targets, and further understanding the overall mechanism of C. albicans pathogenesis are important goals. To study this pathogen it is advantageous to manipulate its genome. Numerous strategies of C. albicans gene manipulation have been introduced. This review evaluates a majority of these strategies and should be a helpful guide for researchers to identify gene targeting strategies to suit their requirements. PMID:21511047

  18. Molecular epidemiology of Candida albicans and its closely related yeasts Candida dubliniensis and Candida africana.

    PubMed

    Romeo, Orazio; Criseo, Giuseppe

    2009-01-01

    We performed a molecular study to determine the occurrence of Candida albicans, Candida africana, and Candida dubliniensis in different clinical samples. The study provides new insights into the epidemiology of candidiasis in hospitalized patients in three hospitals in southern Italy. It also reports the first detailed epidemiological data concerning the occurrence of C. africana in clinical samples.

  19. Molecular Epidemiology of Candida albicans and Its Closely Related Yeasts Candida dubliniensis and Candida africana▿

    PubMed Central

    Romeo, Orazio; Criseo, Giuseppe

    2009-01-01

    We performed a molecular study to determine the occurrence of Candida albicans, Candida africana, and Candida dubliniensis in different clinical samples. The study provides new insights into the epidemiology of candidiasis in hospitalized patients in three hospitals in southern Italy. It also reports the first detailed epidemiological data concerning the occurrence of C. africana in clinical samples. PMID:18987171

  20. Candida albicans Biofilms and Human Disease.

    PubMed

    Nobile, Clarissa J; Johnson, Alexander D

    2015-01-01

    In humans, microbial cells (including bacteria, archaea, and fungi) greatly outnumber host cells. Candida albicans is the most prevalent fungal species of the human microbiota; this species asymptomatically colonizes many areas of the body, particularly the gastrointestinal and genitourinary tracts of healthy individuals. Alterations in host immunity, stress, resident microbiota, and other factors can lead to C. albicans overgrowth, causing a wide range of infections, from superficial mucosal to hematogenously disseminated candidiasis. To date, most studies of C. albicans have been carried out in suspension cultures; however, the medical impact of C. albicans (like that of many other microorganisms) depends on its ability to thrive as a biofilm, a closely packed community of cells. Biofilms are notorious for forming on implanted medical devices, including catheters, pacemakers, dentures, and prosthetic joints, which provide a surface and sanctuary for biofilm growth. C. albicans biofilms are intrinsically resistant to conventional antifungal therapeutics, the host immune system, and other environmental perturbations, making biofilm-based infections a significant clinical challenge. Here, we review our current knowledge of biofilms formed by C. albicans and closely related fungal species. PMID:26488273

  1. Candida albicans escapes from mouse neutrophils.

    PubMed

    Ermert, David; Niemiec, Maria J; Röhm, Marc; Glenthøj, Andreas; Borregaard, Niels; Urban, Constantin F

    2013-08-01

    Candida albicans, the most commonly isolated human fungal pathogen, is able to grow as budding yeasts or filamentous forms, such as hyphae. The ability to switch morphology has been attributed a crucial role for the pathogenesis of C. albicans. To mimic disseminated candidiasis in humans, the mouse is the most widely used model organism. Neutrophils are essential immune cells to prevent opportunistic mycoses. To explore potential differences between the rodent infection model and the human host, we compared the interactions of C. albicans with neutrophil granulocytes from mice and humans. We revealed that murine neutrophils exhibited a significantly lower ability to kill C. albicans than their human counterparts. Strikingly, C. albicans yeast cells formed germ tubes upon internalization by murine neutrophils, eventually rupturing the neutrophil membrane and thereby, killing the phagocyte. On the contrary, growth and subsequent escape of C. albicans are blocked inside human neutrophils. According to our findings, this blockage in human neutrophils might be a result of higher levels of MPO activity and the presence of α-defensins. We therefore outline differences in antifungal immune defense between humans and mouse strains, which facilitates a more accurate interpretation of in vivo results.

  2. The parasexual lifestyle of Candida albicans.

    PubMed

    Bennett, Richard J

    2015-12-01

    Candida albicans is both a prevalent human commensal and the most commonly encountered human fungal pathogen. This lifestyle is dependent on the ability of the fungus to undergo rapid genetic and epigenetic changes, often in response to specific environmental cues. A parasexual cycle in C. albicans has been defined that includes several unique properties when compared to the related model yeast, Saccharomyces cerevisiae. Novel features include strict regulation of mating via a phenotypic switch, enhanced conjugation within a sexual biofilm, and a program of concerted chromosome loss in place of a conventional meiosis. It is expected that several of these adaptations co-evolved with the ability of C. albicans to colonize the mammalian host.

  3. A Candida albicans PeptideAtlas

    PubMed Central

    Vialas, Vital; Sun, Zhi; Penha, Carla Verónica Loureiro y; Carrascal, Montserrat; Abian, Joaquin; Monteoliva, Lucía; Deutsch, Eric W.; Aebersold, Ruedi; Moritz, Robert L.; Gil, Concha

    2013-01-01

    Candida albicans public proteomic data sets, though growing steadily in the last few years, still have a very limited presence in online repositories. We report here the creation of a C. albicans PeptideAtlas comprising near 22000 distinct peptides at a 0.24 % False Discovery Rate (FDR) that account for over 2500 canonical proteins at a 1.2% FDR. Based on data from 16 experiments, we attained coverage of 41% of the C.albicans open reading frame sequences (ORFs) in the database used for the searches. This PeptideAtlas provides several useful features, including comprehensive protein and peptide-centered search capabilities and visualization tools that establish a solid basis for the study of basic biological mechanisms key to virulence and pathogenesis such as dimorphism, adherence, and apoptosis. Further, it is a valuable resource for the selection of candidate proteotypic peptides for targeted proteomic experiments via selected reaction monitoring (SRM) or SWATH-MS. PMID:23811049

  4. Candida albicans adhesion to composite resin materials.

    PubMed

    Bürgers, Ralf; Schneider-Brachert, Wulf; Rosentritt, Martin; Handel, Gerhard; Hahnel, Sebastian

    2009-09-01

    The adhesion of Candida albicans to dental restorative materials in the human oral cavity may promote the occurrence of oral candidosis. This study aimed to compare the susceptibility of 14 commonly used composite resin materials (two compomers, one ormocer, one novel silorane, and ten conventional hybrid composites) to adhere Candida albicans. Differences in the amount of adhering fungi should be related to surface roughness, hydrophobicity, and the type of matrix. Cylindrical specimens of each material were made according to the manufacturers' instructions. Surface roughness R (a) was assessed by perthometer measurements and the degree of hydrophobicity by computerized contact angle analysis. Specimens were incubated with a reference strain of C. albicans (DMSZ 1386), and adhering fungi were quantified by using a bioluminometric assay in combination with an automated plate reader. Statistical differences were analyzed by the Kruskal-Wallis test and Mann-Whitney U test. Spearman's rank correlation coefficients were calculated to assess correlations. Median R (a) of the tested composite resin materials ranged between 0.04 and 0.23 microm, median contact angles between 69.2 degrees and 86.9 degrees . The two compomers and the ormocer showed lower luminescence intensities indicating less adhesion of fungi than all tested conventional hybrid composites. No conclusive correlation was found between surface roughness, hydrophobicity, and the amount of adhering C. albicans.

  5. Adherence ability of Candida africana: a comparative study with Candida albicans and Candida dubliniensis.

    PubMed

    Romeo, Orazio; De Leo, Filomena; Criseo, Giuseppe

    2011-07-01

    In this study, we compared the adherence ability to human Hela cells and biofilm formation of three closely related Candida yeast. In our experiments, Candida africana showed poor adhesion ability to human Hela cells and the absence of biofilm formation on polyvinyl chloride strips. Conversely, Candida albicans and Candida dubliniensis formed mature biofilms and stable attachment to Hela cells. To our knowledge, this is the first comparative study reporting data on biofilm formation and adherence to human Hela cells by C. africana.

  6. Candida species biofilm and Candida albicans ALS3 polymorphisms in clinical isolates.

    PubMed

    Bruder-Nascimento, Ariane; Camargo, Carlos Henrique; Mondelli, Alessandro Lia; Sugizaki, Maria Fátima; Sadatsune, Terue; Bagagli, Eduardo

    2014-01-01

    Over the last decades, there have been important changes in the epidemiology of Candida infections. In recent years, Candida species have emerged as important causes of invasive infections mainly among immunocompromised patients. This study analyzed Candida spp. isolates and compared the frequency and biofilm production of different species among the different sources of isolation: blood, urine, vulvovaginal secretions and peritoneal dialysis fluid. Biofilm production was quantified in 327 Candida isolates obtained from patients attended at a Brazilian tertiary public hospital (Botucatu, Sao Paulo). C. albicans ALS3 gene polymorphism was also evaluated by determining the number of repeated motifs in the central domain. Of the 198 total biofilm-positive isolates, 72 and 126 were considered as low and high biofilm producers, respectively. Biofilm production by C. albicans was significantly lower than that by non-albicans isolates and was most frequently observed in C. tropicalis. Biofilm production was more frequent among bloodstream isolates than other clinical sources, in urine, the isolates displayed a peculiar distribution by presenting two distinct peaks, one containing biofilm-negative isolates and the other containing isolates with intense biofilm production. The numbers of tandem-repeat copies per allele were not associated with biofilm production, suggesting the evolvement of other genetic determinants.

  7. Adherence and receptor relationships of Candida albicans.

    PubMed Central

    Calderone, R A; Braun, P C

    1991-01-01

    The cell surface of Candida albicans is composed of a variety of polysaccharides such as glucan, chitin, and mannan. The first two components primarily provide structure, while the mannan, often covalently linked to protein, constitutes the major antigen of the organism. Mannoproteins also have enzymatic activity (acid protease) and ligand-receptor functions. The complement receptors of C. albicans appear to be mannoproteins that are required for the adherence of the organism to endothelial cells. This is certainly true of the CR3-like protein of C. albicans. Proof that the CR3 is the Candida receptor for endothelial cells is derived from two observations. First, mutants lacking CR3 activity are less adherent in vitro and, in fact, less virulent. Second, the ligand recognized by the CR3 receptor (C3bi) as well as anti-CR3 antibodies blocks adherence of the organism to endothelial cells. The CR2 of C. albicans appears to promote the adherence of the organism to plastic substrates. Unlike the CR2 of mammalian cells, the Candida CR2 recognizes ligands containing the RGD sequence of amino acids in addition to the C3d ligand, which does not contain the RGD sequence. There is uncertainty as to whether the Candida CR2 and CR3 are, in fact, different proteins. A mannoprotein has also been described as the adhesin for epithelial cells. In this case, the receptor has a lectinlike activity and recognizes fucose- or glucosamine-containing glycoproteins of epithelial cells, depending on the strain of C. albicans. The oligosaccharide component of the receptor is probably not involved in ligand recognition and may serve to stabilize the receptor. However, the oligosaccharide factor 6 epitope of mannan may also provide adhesin activity in the recognition of epithelial cells. Mannoproteins can be extracted from cells by a number of reagents. Zymolyase, for instance, tends to remove structural mannoproteins, which contain relatively little protein and are linked to glucan. Reagents

  8. Proteolytic activity and cytokine up-regulation by non-albicans Candida albicans.

    PubMed

    Nawaz, Ali; Pärnänen, Pirjo; Kari, Kirsti; Meurman, Jukka H

    2015-05-01

    Mouth is an important source of infections and oral infections such as Candida infections increase the risk of mortality. Our purpose was to investigate differences in proteolytic activity of non-albicans Candida albicans (non-albicans Candida) between clinical isolates and laboratory samples. The second aim was to assess the concentration of pro- and anti-inflammatory cytokine levels IL-1β, IL-10, and TNF-α in saliva of patients with the non-albicans Candida and Candida-negative saliva samples. Clinical yeast samples from our laboratory were used for analyses. Candida strains were grown in YPG at 37 °C for 24 h in water bath with shaking. The activity of Candida proteinases of cell and cell-free fractions were analyzed by MDPF-gelatin zymography. The levels of IL-1β, IL-10, and TNF-α were measured from saliva with ELISA. The study showed differences in the proteolytic activity among the non-albicans Candida strains. C. tropicalis had higher proteolytic activity when compared to the other strains. Significant difference was found in salivary IL-1β levels between the non-albicans Candida and control strains (P < 0.002). The present findings showed differences in proteolytic activity among the non-albicans Candida strains. The increased IL-1β concentration may be one of the host response components associated with non-albicans Candida infection.

  9. Coaggregation of Candida albicans, Actinomyces naeslundii and Streptococcus mutans is Candida albicans strain dependent.

    PubMed

    Arzmi, Mohd Hafiz; Dashper, Stuart; Catmull, Deanne; Cirillo, Nicola; Reynolds, Eric C; McCullough, Michael

    2015-08-01

    Microbial interactions are necessarily associated with the development of polymicrobial oral biofilms. The objective of this study was to determine the coaggregation of eight strains of Candida albicans with Actinomyces naeslundii and Streptococcus mutans. In autoaggregation assays, C. albicans strains were grown in RPMI-1640 and artificial saliva medium (ASM) whereas bacteria were grown in heart infusion broth. C. albicans, A. naeslundii and S. mutans were suspended to give 10(6), 10(7) and 10(8) cells mL(-1) respectively, in coaggregation buffer followed by a 1 h incubation. The absorbance difference at 620 nm (ΔAbs) between 0 h and 1 h was recorded. To study coaggregation, the same protocol was used, except combinations of microorganisms were incubated together. The mean ΔAbs% of autoaggregation of the majority of RPMI-1640-grown C. albicans was higher than in ASM grown. Coaggregation of C. albicans with A. naeslundii and/or S. mutans was variable among C. albicans strains. Scanning electron microscopy images showed that A. naeslundii and S. mutans coaggregated with C. albicans in dual- and triculture. In conclusion, the coaggregation of C. albicans, A. naeslundii and S. mutans is C. albicans strain dependent.

  10. Direct Isolation of Candida spp. from Blood Cultures on the Chromogenic Medium CHROMagar Candida

    PubMed Central

    Horvath, Lynn L.; Hospenthal, Duane R.; Murray, Clinton K.; Dooley, David P.

    2003-01-01

    CHROMagar Candida is a selective and differential chromogenic medium that has been shown to be useful for identification of Candida albicans, Candida krusei, Candida tropicalis, and perhaps Candida glabrata. Colony morphology and color have been well defined when CHROMagar Candida has been used to isolate yeast directly from clinical specimens, including stool, urine, respiratory, vaginal, oropharyngeal, and esophageal sources. Direct isolation of yeast on CHROMagar Candida from blood cultures has not been evaluated. We evaluated whether the color and colony characteristics produced by Candida spp. on CHROMagar Candida were altered when yeasts were isolated directly from blood cultures. Fifty clinical isolates of Candida were inoculated into aerobic and anaerobic blood culture bottles and incubated at 35°C in an automated blood culture system. When growth was detected, an aliquot was removed and plated onto CHROMagar Candida. As a control, CHROMagar Candida plates were inoculated with the same isolate of yeast grown on Sabouraud dextrose agar simultaneously. No significant difference was detected in color or colony morphology between the blood and control isolates in any of the tested organisms. All C. albicans (n = 12), C. tropicalis (n = 12), C. glabrata (n = 9), and C. krusei (n = 5) isolates exhibited the expected species-specific colony characteristics and color, whether isolated directly from blood or from control cultures. CHROMagar Candida can be reliably used for direct isolation of yeast from blood cultures. Direct isolation could allow mycology laboratories to more rapidly identify Candida spp., enable clinicians to more quickly make antifungal agent selections, and potentially decrease patient morbidity and mortality. PMID:12791890

  11. In vitro pharmacodynamic modelling of anidulafungin against Candida spp.

    PubMed

    Gil-Alonso, Sandra; Jauregizar, Nerea; Ortega, Ignacio; Eraso, Elena; Suárez, Elena; Quindós, Guillermo

    2016-03-01

    The aim of this study was to fit anidulafungin in vitro static time-kill data from nine strains of Candida with a pharmacodynamic (PD) model in order to describe the antifungal activity of this drug against Candida spp. Time-kill data from strains of Candida albicans, Candida glabrata and Candida parapsilosis clades were best fit using an adapted sigmoidal Emax model and resulted in a set of PD parameters (Emax, EC50 and Hill factor) for each fungal strain. The data were analysed with NONMEM 7. Anidulafungin was effective in a species- and concentration-dependent manner against the strains of C. glabrata and C. parapsilosis clades as observed with the EC50 estimates. Maximum killing rate constant (Emax) values were higher against C. glabrata and C. parapsilosis complex strains. In conclusion, we demonstrated that the activity of anidulafungin against Candida can be accurately described using an adapted sigmoidal Emax model.

  12. Effect of Tetrandrine against Candida albicans Biofilms

    PubMed Central

    Zhao, Lan-Xue; Li, De-Dong; Hu, Dan-Dan; Hu, Gan-Hai; Yan, Lan; Wang, Yan; Jiang, Yuan-Ying

    2013-01-01

    Candida albicans is the most common human fungal pathogen and has a high propensity to develop biofilms that are resistant to traditional antifungal agents. In this study, we investigated the effect of tetrandrine (TET) on growth, biofilm formation and yeast-to-hypha transition of C. albicans. We characterized the inhibitory effect of TET on hyphal growth and addressed its possible mechanism of action. Treatment of TET at a low concentration without affecting fungal growth inhibited hyphal growth in both liquid and solid Spider media. Real-time RT-PCR revealed that TET down-regulated the expression of hypha-specific genes ECE1, ALS3 and HWP1, and abrogated the induction of EFG1 and RAS1, regulators of hyphal growth. Addition of cAMP restored the normal phenotype of the SC5314 strain. These results indicate that TET may inhibit hyphal growth through the Ras1p-cAMP-PKA pathway. In vivo, at a range of concentrations from 4 mg/L to 32 mg/L, TET prolonged the survival of C. albicans-infected Caenorhabditis elegans significantly. This study provides useful information for the development of new strategies to reduce the incidence of C. albicans biofilm-associated infections. PMID:24260276

  13. Germination of Candida albicans induced by proline.

    PubMed Central

    Dabrowa, N; Taxer, S S; Howard, D H

    1976-01-01

    Blastospores of Candida albicans germinated in proline-biotin-buffer medium incubated at 37 C. Certain other amino acids in the glatamate, asparate, and pyruvate families also fostered germinaton but generally to a lesser extent than did proline. L-Cysteine, D-proline, and certain structural analogues of L-proline inhibited proline-stimualted germination. The concentration of phosphate and glucose was crucial to amino acid-stimulated germination of C. albicans. Clinical isolates and stock cultures varied in their response to the germ tube-inducing activity of proline or other amino acids. The proline-buffer medium cannot be used in a diagnostic test for production of germ tubes by isolates of yeasts. PMID:5375

  14. Inhibition of Candida albicans by Lactobacillus acidophilus.

    PubMed

    Collins, E B; Hardt, P

    1980-05-01

    Candida albicans grew at pH 4.6 or above in nutrient broth containing 5% glucose but was retarded at pH 7.7 by filtrates of Lactobacillus acidophilus grown in casitone broth. Vaginal implantation of nonfermented acidophilus milk, yogurt, or low-fat milk for preventing recurrence of monilia vaginitis subsequent to treatment with Nystatin was studied with 30 women. Reinfections within 3 mo according to product received were: no milk product, 3; yogurt, 1; nonfermented acidophilus milk, 1; and low-fat milk, 0. PMID:6771309

  15. Melittin induces apoptotic features in Candida albicans

    SciTech Connect

    Park, Cana; Lee, Dong Gun

    2010-03-26

    Melittin is a well-known antimicrobial peptide with membrane-active mechanisms. In this study, it was found that Melittin exerted its antifungal effect via apoptosis. Candida albicans exposed to Melittin showed the increased reactive oxygen species (ROS) production, measured by DHR-123 staining. Fluorescence microscopy staining with FITC-annexin V, TUNEL and DAPI further confirmed diagnostic markers of yeast apoptosis including phosphatidylserine externalization, and DNA and nuclear fragmentation. The current study suggests that Melittin possesses an antifungal effect with another mechanism promoting apoptosis.

  16. Analysis of the Candida albicans Phosphoproteome

    PubMed Central

    Willger, S. D.; Liu, Z.; Olarte, R. A.; Adamo, M. E.; Myers, L. C.; Kettenbach, A. N.

    2015-01-01

    Candida albicans is an important human fungal pathogen in both immunocompetent and immunocompromised individuals. C. albicans regulation has been studied in many contexts, including morphological transitions, mating competence, biofilm formation, stress resistance, and cell wall synthesis. Analysis of kinase- and phosphatase-deficient mutants has made it clear that protein phosphorylation plays an important role in the regulation of these pathways. In this study, to further our understanding of phosphorylation in C. albicans regulation, we performed a deep analysis of the phosphoproteome in C. albicans. We identified 19,590 unique peptides that corresponded to 15,906 unique phosphosites on 2,896 proteins. The ratios of serine, threonine, and tyrosine phosphosites were 80.01%, 18.11%, and 1.81%, respectively. The majority of proteins (2,111) contained at least two detected phosphorylation sites. Consistent with findings in other fungi, cytoskeletal proteins were among the most highly phosphorylated proteins, and there were differences in Gene Ontology (GO) terms for proteins with serine and threonine versus tyrosine phosphorylation sites. This large-scale analysis identified phosphosites in protein components of Mediator, an important transcriptional coregulatory protein complex. A targeted analysis of the phosphosites in Mediator complex proteins confirmed the large-scale studies, and further in vitro assays identified a subset of these phosphorylations that were catalyzed by Cdk8 (Ssn3), a kinase within the Mediator complex. These data represent the deepest single analysis of a fungal phosphoproteome and lay the groundwork for future analyses of the C. albicans phosphoproteome and specific phosphoproteins. PMID:25750214

  17. Karyotyping of Candida albicans and Candida glabrata from patients with Candida sepsis.

    PubMed

    Klempp-Selb, B; Rimek, D; Kappe, R

    2000-01-01

    The aim of this study was to determine the relatedness of Candida strains from patients suffering from Candida septicaemia by typing of Candida isolates from blood cultures and different body sites by pulsed field gel electrophoresis (PFGE using a contour-clamped homogenous electric field, CHEF). We studied 17 isolates of Candida albicans and 10 isolates of Candida glabrata from six patients. Four patients suffered from a C. albicans septicaemia, one patient from a C. glabrata septicaemia, and one patient had a mixed septicaemia with C. albicans and C. glabrata. Eight isolates from blood cultures were compared with 19 isolates of other sites (stool six, urine four, genital swab four, tip of central venous catheter three, tracheal secretion one, sputum one). PFGE typing resulted in 10 different patterns, four with C. albicans and six with C. glabrata. Five of the six patients had strains of identical PFGE patterns in the blood and at other sites. Seven isolates of a 58-year-old female with a C. glabrata septicaemia fell into five different PFGE patterns. However, they showed minor differences only, which may be due to chromosomal rearrangements within a single strain. Thus it appears, that the colonizing Candida strains were identical to the circulating strains in the bloodstream in at least five of six patients.

  18. Activity of Novel Synthetic Peptides against Candida albicans.

    PubMed

    Lum, Kah Yean; Tay, Sun Tee; Le, Cheng Foh; Lee, Vannajan Sanghiran; Sabri, Nadia Hanim; Velayuthan, Rukumani Devi; Hassan, Hamimah; Sekaran, Shamala Devi

    2015-01-01

    Candida spp. are the most common causes of fungal infections worldwide. Among the Candida species, Candida albicans remains the predominant species that causes invasive candidiasis in most countries. In this study, we used two peptides, KABT-AMP and uperin 3.6 as templates to develop novel antifungal peptides. Their anticandidal activity was assessed using a combination of MIC, time-killing assay and biofilm reduction assay. Hybrid peptides, KU2 and KU3 containing a mixed backbone of KABT-AMP and Uperin 3.6 demonstrated the most potent anticandidal activity with MIC values ranging from 8-16 mg/L. The number of Trp residues and the amphipathic structure of peptides probably enhanced the anticandidal activity of peptides. Increasing the cationicity of the uperin 3.6 analogues resulted in reduced MIC from the range of 64-128 mg/L to 16-64 mg/L and this was also correlated with the antibiofilm activity and killing kinetics of the peptides. Peptides showed synergistic effects when used in combination with conventional antifungals. Peptides demonstrated low haemolytic activity but significant toxicity on two normal human epithelial cell lines. This study provides us with a better understanding on the structure-activity relationship and the balance between cationicity and hydrophobicity of the peptides although the therapeutic application of the peptides is limited. PMID:25965506

  19. 7-hydroxycalamenene Effects on Secreted Aspartic Proteases Activity and Biofilm Formation of Candida spp.

    PubMed Central

    Azevedo, Mariana M. B.; Almeida, Catia A.; Chaves, Francisco C. M.; Rodrigues, Igor A.; Bizzo, Humberto R.; Alviano, Celuta S.; Alviano, Daniela S.

    2016-01-01

    Background: The 7-hydroxycalamenenene-rich essential oil (EO) obtained from the leaves of Croton cajucara (red morphotype) have been described as active against bacteria, protozoa, and fungi species. In this work, we aimed to evaluate the effectiveness of 7-hydroxycalamenenene against Candida albicans and nonalbicans species. Materials and Methods: C. cajucara EO was obtained by hydrodistillation and its major compound, 7-hydroxycalamenene, was purified using preparative column chromatography. The anti-candidal activity was investigated by minimum inhibitory concentration (MIC) and secreted aspartic proteases (SAP) and biofilm inhibition assays. Results: 7-hydroxycalamenene (98% purity) displayed anti-candidal activity against all Candida species tested. Higher activity was observed against Candida dubliniensis, Candida parapsilosis and Candida albicans, showing MIC values ranging from 39.06 μg/ml to 78.12 μg/ml. The purified 7-hydroxycalamenene was able to inhibit 58% of C. albicans ATCC 36801 SAP activity at MIC concentration (pH 7.0). However, 7-hydroxycalamenene demonstrated poor inhibitory activity on C. albicans ATCC 10231 biofilm formation even at the highest concentration tested (2500 μg/ml). Conclusion: The bioactive potential of 7-hydroxycalamenene against planktonic Candida spp. further supports its use for the development of antimicrobials with anti-candidal activity. SUMMARY Croton cajucara Benth. essential oil provides high amounts of 7-hydroxycalamenene7-Hydroxycalameneneisolated from C. cajucarais active against Candida spp7-Hydroxycalameneneinhibits C. albicans aspartic protease activity7-Hydroxycalamenene was not active against C. albicans biofilm formation. Figure PMID:27019560

  20. Diallyl disulphide depletes glutathione in Candida albicans

    PubMed Central

    Lemar, Katey M.; Aon, Miguel A.; Cortassa, Sonia; O’Rourke, Brian; T. Müller, Carsten; Lloyd, David

    2008-01-01

    Using two-photon scanning laser microscopy, we investigated the effect of an Allium sativum (garlic) constituent, diallyl disulphide (DADS), on key physiological functions of the opportunistic pathogen Candida albicans. A short 30 min exposure to 0.5 mm DADS followed by removal induced 70% cell death (50% necrotic, 20% apoptotic) within 2 h, increasing to 75% after 4 h. The early intracellular events associated with DADS-induced cell death were monitored with two-photon fluorescence microscopy to track mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS) and NADH or reduced glutathione (GSH) under aerobic conditions. DADS treatment decreased intracellular GSH and elevated intracellular ROS levels. Additionally, DADS induced a marked decrease of ΔΨm and lowered respiration in cell suspensions and isolated mitochondria. In vitro kinetic experiments in cell-free extracts suggest that glutathione-S-transferase (GST) is one of the intracellular targets of DADS. Additional targets were also identified, including inhibition of a site or sites between complexes II-IV in the electron transport chain, as well as the mitochondrial ATP-synthase. The results indicate that DADS is an effective antifungal agent able to trigger cell death in Candida, most probably by eliciting oxidative stress as a consequence of thiol depletion and impaired mitochondrial function. PMID:17534841

  1. Postantifungal effect of caspofungin against the Candida albicans and Candida parapsilosis clades.

    PubMed

    Gil-Alonso, Sandra; Jauregizar, Nerea; Eraso, Elena; Quindós, Guillermo

    2016-10-01

    Killing and postantifungal effects could be relevant for the selection of optimal dosing schedules. This study aims to compare time-kill and postantifungal effects with caspofungin on Candida albicans (C. albicans, Candida dubliniensis, Candida africana) and Candida parapsilosis (C. parapsilosis, Candida metapsilosis, Candida orthopsilosis) clades. In the postantifungal effect experiments, strains were exposed to caspofungin for 1 h at concentrations 0.12-8 μg/mL. Time-kill experiments were conducted at the same concentrations. Caspofungin exhibited a significant and prolonged postantifungal effect (>37 h) with 2 μg/mL against the most strains of C. albicans clade. Against the C. parapsilosis clade, the postantifungal effect was <12 h at 8 μg/mL, except for two strains. Caspofungin was fungicidal against C. albicans, C. dubliniensis and C. metapsilosis. PMID:27492134

  2. Postantifungal effect of caspofungin against the Candida albicans and Candida parapsilosis clades.

    PubMed

    Gil-Alonso, Sandra; Jauregizar, Nerea; Eraso, Elena; Quindós, Guillermo

    2016-10-01

    Killing and postantifungal effects could be relevant for the selection of optimal dosing schedules. This study aims to compare time-kill and postantifungal effects with caspofungin on Candida albicans (C. albicans, Candida dubliniensis, Candida africana) and Candida parapsilosis (C. parapsilosis, Candida metapsilosis, Candida orthopsilosis) clades. In the postantifungal effect experiments, strains were exposed to caspofungin for 1 h at concentrations 0.12-8 μg/mL. Time-kill experiments were conducted at the same concentrations. Caspofungin exhibited a significant and prolonged postantifungal effect (>37 h) with 2 μg/mL against the most strains of C. albicans clade. Against the C. parapsilosis clade, the postantifungal effect was <12 h at 8 μg/mL, except for two strains. Caspofungin was fungicidal against C. albicans, C. dubliniensis and C. metapsilosis.

  3. Investigation of ERG11 gene expression among fluconazole-resistant Candida albicans: first report from an Iranian referral paediatric hospital.

    PubMed

    Teymuri, M; Mamishi, S; Pourakbari, B; Mahmoudi, S; Ashtiani, M T; Sadeghi, R H; Yadegari, M H

    2015-01-01

    The multiplicity of mechanisms of resistance to azole antifungal agents has been described. As fluconazole-resistant clinical Candida albicans isolates that constitutively over-express ERG11 have been identified in previous studies, the aim of this study is to investigate this molecular mechanism involved in fluconazole resistance of C. albicans clinical isolates. Fluconazole susceptibility testing was carried out on clinical isolates of Candida spp. obtained from hospitalised children in an Iranian referral children's hospital. A polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) technique was used to differentiate Candida spp. The resistant C. albicans isolates were subjected to RT-qPCR using primers that identify ERG11 gene expression. Of the 142 Candida spp. isolates studied, C. albicans was the most predominant isolate, occurring in 68.3% (97/142) of the patients. According to the CLSI method, the majority of the C. albicans isolates (91.7%, 89/97), categorised as susceptible (minimum inhibitory concentration [MIC] ≤8 μg/mL), five isolates were considered resistant (MIC ≤64 μg/mL) and three had dose-dependent susceptibility (MIC = 8.16-32 μg/mL). The ERG11 gene in the five fluconazole-resistant C. albicans isolates was upregulated 4.15-5.84-fold relative to the ATCC 10231 control strain. In this study, the expression of ERG11 was upregulated in all the fluconazole-resistant C. albicans isolates. There are limited data on the antifungal susceptibility of Candida spp. as well as the molecular mechanism of azole resistance in Iran, especially for isolates causing infections in children. Therefore, the surveillance of antifungal resistance patterns and investigation of other mechanisms of azole resistance in all Candida spp. isolates is recommended.

  4. Correlation of atherogenesis with an infection of Candida albicans

    PubMed Central

    Nurgeldiyeva, Maya J; Hojakuliyev, Bayram G; Muhammedov, Merdan B

    2014-01-01

    Purpose: To study contents of atherosclerotic plaques for the presence of fungi of the genus Candida; and an analysis of some immunological and biochemical indices in patients with acute coronary syndrome (ACS) that are positive for Candida albicans. Materials and methods: To test for the presence of fungi in an atherosclerotic plaque, we used a method developed by us (patent NO 531, a priority from 6/28/2010). A total of 47 atherosclerotic plaques were obtained during 20 autopsies. In addition, 80 individuals (58 male, 22 female; age range from 29 to 85) with acute coronary syndrome were subjected to a blood biochemical test, including quantification of TNF-α levels and IgG and IgM to Candida albicans was determined. Results: Fungi of the genus Candida were identified in 31.9% (15 out of 47) of atherosclerotic plaques. Particularly, Candida krusii and Candida grabrata were identified in overwhelming majority, although solitary colonies of Candida tropicalis and a single colony of Candida albicans were also detected. 80 (100%) patients were negative for IgM, but 30 (37.5%) were positive for IgG to Candida albicans. TNF-α was detected in a smaller quantity of IgG-negative patients (36.7%) relative to patients of IgG-positive group (70%), however its levels were considerably above in the first group (511.73±195.80 pg/ml) than in the second one (326.68±259.91 pg/ml, P < 0.05). Differences in the levels of ASAT and ALAT in patients positive to Candida albicans and negative for TNF-α were significantly higher than in the rest of patients. Conclusion: It is conceivable that fungi of the genus Candida are capable of inducing an inflammation of the vascular wall that in turn can lead to the development of atherosclerosis. PMID:25232398

  5. Study on the comparative activity of echinocandins on murine gut colonization by Candida albicans.

    PubMed

    Maraki, Sofia; Hamilos, George; Dimopoulou, Dimitra; Andrianaki, Angeliki M; Karageorgiadis, Alexander Steven; Kyvernitakis, Andreas; Lionakis, Stelios; Kofteridis, Diamantis P; Samonis, George

    2015-08-01

    Colonization of the gastrointestinal (GI) tract by Candida species is a principal pathogenetic event for development of invasive candidiasis. Importantly, the effect of echinocandins, the preferred antifungal agents for treatment of invasive candidiasis, on GI tract colonization by Candida spp. is currently unknown. Herein, we used an established model of persistent murine GI tract colonization by Candida albicans to test the ability of different echinocandins to eradicate the yeast from murine gut. Adult male Crl:CD1 (ICR) BR mice were fed with chow containing C. albicans and subsequently treated with different echinocandins or normal saline via daily intraperitoneal injections for 10 days. Quantitative stool cultures were performed immediately before (week one), and weekly for three months after discontinuation of treatment. Notably, treatment with all three echinocandins used (caspofungin, anidulafungin, and micafungin) resulted in eradication of Candida albicans from the stools, as evidenced by the significant reduction of yeast cells from a mean of 4.2 log10 CFU/g of stool before treatment (week one of colonization) to undetectable (<2 log10 CFU/g of stool) levels (week 12, P < 0.0001). In contrast, there was no significant reduction of Candida yeast cells in the stools of control mice. Collectively, the ability of echinocandins to eradicate C. albicans from the stools could have important implications in prophylaxis of high-risk patients for development of invasive candidiasis originating from the GI tract.

  6. High-frequency switching in Candida albicans.

    PubMed Central

    Soll, D R

    1992-01-01

    Most strains of Candida albicans are capable of switching frequently and reversibly between a number of phenotypes distinguishable by colony morphology. A number of different switching systems have been defined according to the limited set of phenotypes in each switching repertoire, and each strain appears to possess a single system. Switching can affect many aspects of cellular physiology and morphology and appears to be a second level of phenotypic variability superimposed upon the bud-hypha transition. The most dramatic switching system so far identified is the "white-opaque transition." This system dramatizes the extraordinary effects switching can have on the budding cell phenotype, including the synthesis of opaque-specific antigens, the expression of white-specific and opaque-specific genes, and the genesis of unique cell wall structures. Switching has been demonstrated to occur at sites of infection and between episodes of recurrent vaginitis, and it may function to generate variability in commensal and infecting populations for adaptive reasons. Although the molecular mechanisms involved in the switch event are not understood, recent approaches to its elucidation are discussed and an epigenetic mechanism is proposed. Images PMID:1576587

  7. Chlorhexidine markedly potentiates the oxidants scavenging abilities of Candida albicans.

    PubMed

    Ginsburg, I; Koren, E; Feuerstein, O; Zogakis, I P; Shalish, M; Gorelik, S

    2015-10-01

    The oxidant scavenging ability (OSA) of catalase-rich Candida albicans is markedly enhanced by chlorhexidine digluconate (CHX), polymyxin B, the bile salt ursodeoxycholate and by lysophosphatidylcholine, which all act as detergents facilitating the penetration of oxidants and their intracellular decomposition. Quantifications of the OSA of Candida albicans were measured by a highly sensitive luminol-dependent chemiluminescence assay and by the Thurman's assay, to quantify hydrogen peroxide (H2O2). The OSA enhancing activity by CHX depends to some extent on the media on which candida grew. The OSA of candida treated by CHX was modulated by whole human saliva, red blood cells, lysozyme, cationic peptides and by polyphenols. Concentrations of CHX, which killed over 95 % of Candida albicans cells, did not affect the cells' abilities to scavenge reactive oxygen species (ROS). The OSA of Candida cells treated by CHX is highly refractory to H2O2 (50 mM) but is strongly inhibited by hypochlorous acid, lecithin, trypan blue and by heparin. We speculate that similarly to catalase-rich red blood cells, Candida albicans and additional catalase-rich microbiota may also have the ability to scavenge oxidants and thus can protect catalase-negative anaerobes and facultative anaerobes cariogenic streptococci against peroxide and thus secure their survival in the oral cavity.

  8. Chlorhexidine markedly potentiates the oxidants scavenging abilities of Candida albicans.

    PubMed

    Ginsburg, I; Koren, E; Feuerstein, O; Zogakis, I P; Shalish, M; Gorelik, S

    2015-10-01

    The oxidant scavenging ability (OSA) of catalase-rich Candida albicans is markedly enhanced by chlorhexidine digluconate (CHX), polymyxin B, the bile salt ursodeoxycholate and by lysophosphatidylcholine, which all act as detergents facilitating the penetration of oxidants and their intracellular decomposition. Quantifications of the OSA of Candida albicans were measured by a highly sensitive luminol-dependent chemiluminescence assay and by the Thurman's assay, to quantify hydrogen peroxide (H2O2). The OSA enhancing activity by CHX depends to some extent on the media on which candida grew. The OSA of candida treated by CHX was modulated by whole human saliva, red blood cells, lysozyme, cationic peptides and by polyphenols. Concentrations of CHX, which killed over 95 % of Candida albicans cells, did not affect the cells' abilities to scavenge reactive oxygen species (ROS). The OSA of Candida cells treated by CHX is highly refractory to H2O2 (50 mM) but is strongly inhibited by hypochlorous acid, lecithin, trypan blue and by heparin. We speculate that similarly to catalase-rich red blood cells, Candida albicans and additional catalase-rich microbiota may also have the ability to scavenge oxidants and thus can protect catalase-negative anaerobes and facultative anaerobes cariogenic streptococci against peroxide and thus secure their survival in the oral cavity. PMID:26223507

  9. Application of CHROMagar Candida for rapid screening of clinical specimens for Candida albicans, Candida tropicalis, Candida krusei, and Candida (Torulopsis) glabrata.

    PubMed Central

    Pfaller, M A; Houston, A; Coffmann, S

    1996-01-01

    CHROMagar Candida is a new differential culture medium that allows selective isolation of yeasts and simultaneously identifies colonies of Candida albicans, C. tropicalis, and C. krusei. We evaluated the use of this medium with 316 yeast isolates including 247 isolated directly on CHROMagar from clinical material. Over 95% of stock and clinical isolates of C. albicans, C. tropicalis, and C. krusei were correctly identified on the basis of colony morphology and pigmentation on CHROMagar. Additionally, CHROMagar also allowed the identification of C. (Torulopsis) glabrata at a similar level of accuracy. The overall agreement between two observers in reading the CHROMagar plates was 95%. Growth of Candida sp. isolates on CHROMagar had no adverse effect on antifungal MICs or Vitek identification results. In parallel, cultures of 548 stool and rectal swab specimens set up on CHROMagar and Sabouraud glucose agar (SGA) were positive in 234 instances. CHROMagar was positive and SGA was negative for 11 specimens, and CHROMagar was negative and SGA was positive for 18 specimens. A single yeast species was isolated on both media from 162 specimens, and in 146 (90%) of these specimens the same species was detected on both CHROMagar and SGA. A total of 43 of the 234 positive cultures contained mixtures of yeast species. Twenty (47%) of these mixed cultures were detected only on CHROMagar. CHROMagar is extremely useful in making a rapid presumptive identification of common yeast species. This capability plus the ability to detect mixed cultures of Candida spp. promises to improve and streamline the work flow in the mycology and clinical microbiology laboratory. PMID:8748273

  10. Synthetic arylquinuclidine derivatives exhibit antifungal activity against Candida albicans, Candida tropicalis and Candida parapsilopsis

    PubMed Central

    2011-01-01

    Background Sterol biosynthesis is an essential pathway for fungal survival, and is the biochemical target of many antifungal agents. The antifungal drugs most widely used to treated fungal infections are compounds that inhibit cytochrome P450-dependent C14α-demethylase (CYP51), but other enzymes of this pathway, such as squalene synthase (SQS) which catalyses the first committed step in sterol biosynthesis, could be viable targets. The aim of this study was to evaluate the antifungal activity of SQS inhibitors on Candida albicans, Candida tropicalis and Candida parapsilopsis strains. Methods Ten arylquinuclidines that act as SQS inhibitors were tested as antiproliferative agents against three ATCC strains and 54 clinical isolates of Candida albicans, Candida tropicalis and Candida parapsilopsis. Also, the morphological alterations induced in the yeasts by the experimental compounds were evaluated by fluorescence and transmission electron microscopy. Results The most potent arylquinuclidine derivative (3-[1'-{4'-(benzyloxy)-phenyl}]-quinuclidine-2-ene) (WSP1267) had a MIC50 of 2 μg/ml for all species tested and MIC90 varying from 4 μg/ml to 8 μg/ml. Ultrathin sections of C. albicans treated with 1 μg/ml of WSP1267 showed several ultrastructural alterations, including (a) loss of cell wall integrity, (b) detachment of the plasma membrane from the fungal cell wall, (c) accumulation of small vesicles in the periplasmic region, (d) presence of large electron-dense vacuoles and (e) significantly increased cell size and cell wall thickness. In addition, fluorescence microscopy of cells labelled with Nile Red showed an accumulation of lipid droplets in the cytoplasm of treated yeasts. Nuclear staining with DAPI revealed the appearance of uncommon yeast buds without a nucleus or with two nuclei. Conclusion Taken together, our data demonstrate that arylquinuclidine derivatives could be useful as lead compounds for the rational synthesis of new antifungal drugs. PMID

  11. Yeasts isolated from Algerian infants's feces revealed a burden of Candida albicans species, non-albicans Candida species and Saccharomyces cerevisiae.

    PubMed

    Seddik, Hamza Ait; Ceugniez, Alexandre; Bendali, Farida; Cudennec, Benoit; Drider, Djamel

    2016-01-01

    This study aimed at showing the yeast diversity in feces of Algerian infants, aged between 1 and 24 months, hospitalized at Bejaia hospital (northeast side of the country). Thus, 20 colonies with yeast characteristics were isolated and identified using biochemical (ID32C Api system) and molecular (sequencing of ITS1-5.8S-ITS2 region) methods. Almost all colonies isolated (19 strains) were identified as Candida spp., with predominance of Candida albicans species, and one strain was identified as Saccharomyces cerevisiae. Screening of strains with inhibitory activities unveiled the potential of Candida parapsilosis P48L1 and Candida albicans P51L1 to inhibit the growth of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923. Further studies performed with these two Candida strains revealed their susceptibility to clinically used antifungal compounds and were then characterized for their cytotoxicity and hemolytic properties. On the other hand, Saccharomyces cerevisiae P9L1 isolated as well in this study was shown to be devoid of antagonism but resulted safe and overall usable as probiotic.

  12. Global Identification of Biofilm-Specific Proteolysis in Candida albicans

    PubMed Central

    Winter, Michael B.; Salcedo, Eugenia C.; Lohse, Matthew B.; Hartooni, Nairi; Gulati, Megha; Sanchez, Hiram; Takagi, Julie; Hube, Bernhard; Andes, David R.

    2016-01-01

    ABSTRACT Candida albicans is a fungal species that is part of the normal human microbiota and also an opportunistic pathogen capable of causing mucosal and systemic infections. C. albicans cells proliferate in a planktonic (suspension) state, but they also form biofilms, organized and tightly packed communities of cells attached to a solid surface. Biofilms colonize many niches of the human body and persist on implanted medical devices, where they are a major source of new C. albicans infections. Here, we used an unbiased and global substrate-profiling approach to discover proteolytic activities produced specifically by C. albicans biofilms, compared to planktonic cells, with the goal of identifying potential biofilm-specific diagnostic markers and targets for therapeutic intervention. This activity-based profiling approach, coupled with proteomics, identified Sap5 (Candidapepsin-5) and Sap6 (Candidapepsin-6) as major biofilm-specific proteases secreted by C. albicans. Fluorogenic peptide substrates with selectivity for Sap5 or Sap6 confirmed that their activities are highly upregulated in C. albicans biofilms; we also show that these activities are upregulated in other Candida clade pathogens. Deletion of the SAP5 and SAP6 genes in C. albicans compromised biofilm development in vitro in standard biofilm assays and in vivo in a rat central venous catheter biofilm model. This work establishes secreted proteolysis as a promising enzymatic marker and potential therapeutic target for Candida biofilm formation. PMID:27624133

  13. In Vitro Activity of Caspofungin against Candida albicans Biofilms

    PubMed Central

    Bachmann, Stefano P.; VandeWalle, Kacy; Ramage, Gordon; Patterson, Thomas F.; Wickes, Brian L.; Graybill, John R.; López-Ribot, José L.

    2002-01-01

    Most manifestations of candidiasis are associated with biofilm formation on biological or inanimate surfaces. Candida albicans biofilms are recalcitrant to treatment with conventional antifungal therapies. Here we report on the activity of caspofungin, a new semisynthetic echinocandin, against C. albicans biofilms. Caspofungin displayed potent in vitro activity against sessile C. albicans cells within biofilms, with MICs at which 50% of the sessile cells were inhibited well within the drug's therapeutic range. Scanning electron microscopy and confocal scanning laser microscopy were used to visualize the effects of caspofungin on preformed C. albicans biofilms, and the results indicated that caspofungin affected the cellular morphology and the metabolic status of cells within the biofilms. The coating of biomaterials with caspofungin had an inhibitory effect on subsequent biofilm development by C. albicans. Together these findings indicate that caspofungin displays potent activity against C. albicans biofilms in vitro and merits further investigation for the treatment of biofilm-associated infections. PMID:12384370

  14. High throughput multiplex-PCR for direct detection and diagnosis of dermatophyte species, Candida albicans and Candida parapsilosis in clinical specimen.

    PubMed

    Vahidnia, Ali; Bekers, Wouter; Bliekendaal, Harry; Spaargaren, Joke

    2015-06-01

    We have developed and validated a multiplex-PCR method for detection of dermatophyte spp., Candida albicans and parapsilosis for routine diagnostics. Our m-PCR showed excellent concordance with culture results in 475 clinical samples. Through the rapid diagnosis by our m-PCR, clinicians are able to initiate adequate antimycotic therapy much earlier.

  15. The inhibitory activity of linalool against the filamentous growth and biofilm formation in Candida albicans.

    PubMed

    Hsu, Chih-Chieh; Lai, Wen-Lin; Chuang, Kuei-Chin; Lee, Meng-Hwan; Tsai, Ying-Chieh

    2013-07-01

    Candida spp. are part of the natural human microbiota, but they also represent important opportunistic human pathogens. Biofilm-associated Candida albicans infections are clinically relevant due to their high levels of resistance to traditional antifungal agents. In this study, we investigated the ability of linalool to inhibit the formation of C. albicans biofilms and reduce existing C. albicans biofilms. Linalool exhibited antifungal activity against C. albicans ATCC 14053, with a minimum inhibitory concentration (MIC) of 8 mM. Sub-MIC concentrations of linalool also inhibited the formation of germ tubes and biofilms in that strain. The defective architecture composition of C. albicans biofilms exposed to linalool was characterized by scanning electron microscopy. The expression levels of the adhesin genes HWP1 and ALS3 were downregulated by linalool, as assessed by real-time RT-PCR. The expression levels of CYR1 and CPH1, which encode components of the cAMP-PKA and MAPK hyphal formation regulatory pathways, respectively, were also suppressed by linalool, as was the gene encoding their upstream regulator, Ras1. The expression levels of long-term hyphae maintenance associated genes, including UME6, HGC1, and EED1, were all suppressed by linalool. These results indicate that linalool may have therapeutic potential in the treatment of candidiasis associated with medical devices because it interferes with the morphological switch and biofilm formation of C. albicans.

  16. Characterization of extracellular nucleotide metabolism in Candida albicans.

    PubMed

    Rodrigues, Lisa; Russo-Abrahão, Thais; Cunha, Rodrigo A; Gonçalves, Teresa; Meyer-Fernandes, José Roberto

    2016-01-01

    Candida albicans is the most frequent agent of human disseminated fungal infection. Ectophosphatase and ectonucleotidase activities are known to influence the infectious potential of several microbes, including other non-albicans species of Candida. With the present work we aim to characterize these ecto-enzymatic activities in C. albicans. We found that C. albicans does not have a classical ecto-5'-nucleotidase enzyme and 5'AMP is cleaved by a phosphatase instead of exclusively by a nucleotidase that also can use 3'AMP as a substrate. Moreover, these enzymatic activities are not dependent on secreted soluble enzymes and change when the yeast cells are under infection conditions, including low pH, and higher temperature and CO2 content.

  17. The influence of photodynamic therapy parameters on the inactivation of Candida spp: in vitro and in vivo studies

    NASA Astrophysics Data System (ADS)

    Alves, F.; Mima, E. G.; Dovigo, L. N.; Bagnato, V. S.; Jorge, J. H.; de Souza Costa, C. A.; Pavarina, A. C.

    2014-04-01

    The influence of parameters of photodynamic therapy (PDT), such as pre-irradiation time (PIT), on the inactivation of Candida spp. was assessed in vitro and in vivo. Suspensions of Candida albicans, Candida tropicalis, Candida krusei and Candida glabrata were treated with Photogem®, incubated for 5, 10 or 15 min and illuminated with a blue LED light. Colonies were cultivated and log values of CFU ml-1 were analyzed by ANOVA and Kruskall-Wallis test. For in vivo evaluation, immunosuppressed mice were inoculated with C. albicans. PDT was performed on the dorsum of the tongue by topical administration of Photogem® and illumination after 5, 10 or 15 min. C. albicans was recovered from the tongue and the number of CFU ml-1 was analyzed by ANOVA and Tukey test. Animals were killed and the tongues were surgically removed for histological analysis. Susceptibility of Candida spp. suspensions to PDT was in decreasing order: C. albicans = C. tropicalis < C. krusei < C. glabrata. No significant difference was observed among the different PIT (p > 0.05), both in vivo and in vitro. A significant reduction (p < 0.05) of log(CFU ml-1) of C. albicans from tongues of mice was observed with no adverse effects in the tissue. PDT was effective to inactivate in vitroCandida spp. and for reduction of C. albicans in vivo, independently of the PIT used.

  18. Recurrent Candida albicans Ventriculitis Treated with Intraventricular Liposomal Amphotericin B.

    PubMed

    Toprak, Demet; Öcal Demir, Sevliya; Kadayifci, Eda Kepenekli; Türel, Özden; Soysal, Ahmet; Bakir, Mustafa

    2015-01-01

    Central nervous system (CNS) infection with Candida is rare but significant because of its high morbidity and mortality. When present, it is commonly seen among immunocompromised and hospitalized patients. Herein, we describe a case of a four-year-old boy with acute lymphoblastic leukemia (ALL) who experienced recurrent Candida albicans meningitis. The patient was treated successfully with intravenous liposomal amphotericin B at first attack, but 25 days after discharge he was readmitted to hospital with symptoms of meningitis. Candida albicans was grown in CFS culture again and cranial magnetic resonance imaging (MRI) showed ventriculitis. We administered liposomal amphotericin B both intravenously and intraventricularly and favorable result was achieved without any adverse effects. Intraventricular amphotericin B may be considered for the treatment of recurrent CNS Candida infections in addition to intravenous administration. PMID:26558119

  19. Recurrent Candida albicans Ventriculitis Treated with Intraventricular Liposomal Amphotericin B

    PubMed Central

    Toprak, Demet; Öcal Demir, Sevliya; Kadayifci, Eda Kepenekli; Türel, Özden; Soysal, Ahmet; Bakir, Mustafa

    2015-01-01

    Central nervous system (CNS) infection with Candida is rare but significant because of its high morbidity and mortality. When present, it is commonly seen among immunocompromised and hospitalized patients. Herein, we describe a case of a four-year-old boy with acute lymphoblastic leukemia (ALL) who experienced recurrent Candida albicans meningitis. The patient was treated successfully with intravenous liposomal amphotericin B at first attack, but 25 days after discharge he was readmitted to hospital with symptoms of meningitis. Candida albicans was grown in CFS culture again and cranial magnetic resonance imaging (MRI) showed ventriculitis. We administered liposomal amphotericin B both intravenously and intraventricularly and favorable result was achieved without any adverse effects. Intraventricular amphotericin B may be considered for the treatment of recurrent CNS Candida infections in addition to intravenous administration. PMID:26558119

  20. Molecular concordance of concurrent Candida albicans candidemia and candiduria.

    PubMed

    Huang, Po-Yen; Hung, Min-Hui; Shie, Shian-Sen; Su, Lin-Hui; Chen, Ke-Yuan; Ye, Jung-Jr; Chiang, Ping-Cheng; Leu, Hsieh-Shong; Huang, Ching-Tai

    2013-07-01

    The significance of candiduria remains unclear. We correlated Candida albicans candidemia with candiduria by molecular genotyping. 33 pairs of concurrent blood and urine C. albicans isolates from 31 adult (≥ 18 years) were genotyped with infrequent-restriction-site PCR. The molecular concordance rates of three major genotypes were 100% for I, 82% for II, and 71% for III. The molecular concordance between concurrent C. albicans candidemia and candiduria was frequent. Our findings substantiate the importance of candiduria in appropriate clinical context as the majority of our patients were from intensive care units.

  1. Relationship between salivary flow rates and Candida albicans counts.

    PubMed

    Navazesh, M; Wood, G J; Brightman, V J

    1995-09-01

    Seventy-one persons (48 women, 23 men; mean age, 51.76 years) were evaluated for salivary flow rates and Candida albicans counts. Each person was seen on three different occasions. Samples of unstimulated whole, chewing-stimulated whole, acid-stimulated parotid, and candy-stimulated parotid saliva were collected under standardized conditions. An oral rinse was also obtained and evaluated for Candida albicans counts. Unstimulated and chewing-stimulated whole flow rates were negatively and significantly (p < 0.001) related to the Candida counts. Unstimulated whole saliva significantly (p < 0.05) differed in persons with Candida counts of 0 versus <500 versus < or = 500. Chewing-stimulated saliva was significantly (p < 0.05) different in persons with 0 counts compared with those with a > or = 500 count. Differences in stimulated parotid flow rates were not significant among different levels of Candida counts. The results of this study reveal that whole saliva is a better predictor than parotid saliva in identification of persons with high Candida albicans counts.

  2. Sensitization of Candida albicans to terbinafine by berberine and berberrubine

    PubMed Central

    LAM, PIKLING; KOK, STANTON HON LUNG; LEE, KENNETH KA HO; LAM, KIM HUNG; HAU, DESMOND KWOK PO; WONG, WAI YEUNG; BIAN, ZHAOXIANG; GAMBARI, ROBERTO; CHUI, CHUNG HIN

    2016-01-01

    Candida albicans (C. albicans) is an opportunistic fungal pathogen, particularly observed in immunocompromised patients. C. albicans accounts for 50–70% of cases of invasive candidiasis in the majority of clinical settings. Terbinafine, an allylamine antifungal drug, has been used to treat fungal infections previously. It has fungistatic activity against C. albicans. Traditional Chinese medicines can be used as complementary medicines to conventional drugs to treat a variety of ailments and diseases. Berberine is a quaternary alkaloid isolated from the traditional Chinese herb, Coptidis Rhizoma, while berberrubine is isolated from the medicinal plant Berberis vulgaris, but is also readily derived from berberine by pyrolysis. The present study demonstrates the possible complementary use of berberine and berberrubine with terbinafine against C. albicans. The experimental findings assume that the potential application of these alkaloids together with reduced dosage of the standard drug would enhance the resulting antifungal potency. PMID:27073630

  3. Protease activities of Candida spp. isolated from otitis externa: preliminary result.

    PubMed

    Arsović, N A; Banko, A V; Dimitrijević, M V; Djordjević, V Z; Milovanović, J P; Arsenijević, V A

    2009-01-01

    Otomycosis is a fungal infection of the ear predominantly caused by Candida and Aspergillus spp. The possible virulence factors of Candida spp. are enzymes, such as proteases, phospholipases, phosphatases and esterase. According to our knowledge, protease production in Candida strains isolated from patients with otomycosis has not been investigated. The present study was aimed at determining in vitro protease activity in 8 strains of Candida spp. (C. parapsilosis, C. famata, C. guilliermondii and C. albicans) isolated from children with otomycosis. A majority of isolated strains 7/8 (87.5%) were protease positive. The protease activity ranged from Pz 0.61 to 0.78. Further investigation is necessary to clarify the contribution of protease production to Candida virulence associated with otomycosis.

  4. Candida glabrata Binding to Candida albicans Hyphae Enables Its Development in Oropharyngeal Candidiasis.

    PubMed

    Tati, Swetha; Davidow, Peter; McCall, Andrew; Hwang-Wong, Elizabeth; Rojas, Isolde G; Cormack, Brendan; Edgerton, Mira

    2016-03-01

    Pathogenic mechanisms of Candida glabrata in oral candidiasis, especially because of its inability to form hyphae, are understudied. Since both Candida albicans and C. glabrata are frequently co-isolated in oropharyngeal candidiasis (OPC), we examined their co-adhesion in vitro and observed adhesion of C. glabrata only to C. albicans hyphae microscopically. Mice were infected sublingually with C. albicans or C. glabrata individually, or with both species concurrently, to study their ability to cause OPC. Infection with C. glabrata alone resulted in negligible infection of tongues; however, colonization by C. glabrata was increased by co-infection or a pre-established infection with C. albicans. Furthermore, C. glabrata required C. albicans for colonization of tongues, since decreasing C. albicans burden with fluconazole also reduced C. glabrata. C. albicans hyphal wall adhesins Als1 and Als3 were important for in vitro adhesion of C. glabrata and to establish OPC. C. glabrata cell wall protein coding genes EPA8, EPA19, AWP2, AWP7, and CAGL0F00181 were implicated in mediating adhesion to C. albicans hyphae and remarkably, their expression was induced by incubation with germinated C. albicans. Thus, we found a near essential requirement for the presence of C. albicans for both initial colonization and establishment of OPC infection by C. glabrata.

  5. Candida glabrata Binding to Candida albicans Hyphae Enables Its Development in Oropharyngeal Candidiasis

    PubMed Central

    Tati, Swetha; Davidow, Peter; McCall, Andrew; Hwang-Wong, Elizabeth; Rojas, Isolde G.; Cormack, Brendan; Edgerton, Mira

    2016-01-01

    Pathogenic mechanisms of Candida glabrata in oral candidiasis, especially because of its inability to form hyphae, are understudied. Since both Candida albicans and C. glabrata are frequently co-isolated in oropharyngeal candidiasis (OPC), we examined their co-adhesion in vitro and observed adhesion of C. glabrata only to C. albicans hyphae microscopically. Mice were infected sublingually with C. albicans or C. glabrata individually, or with both species concurrently, to study their ability to cause OPC. Infection with C. glabrata alone resulted in negligible infection of tongues; however, colonization by C. glabrata was increased by co-infection or a pre-established infection with C. albicans. Furthermore, C. glabrata required C. albicans for colonization of tongues, since decreasing C. albicans burden with fluconazole also reduced C. glabrata. C. albicans hyphal wall adhesins Als1 and Als3 were important for in vitro adhesion of C. glabrata and to establish OPC. C. glabrata cell wall protein coding genes EPA8, EPA19, AWP2, AWP7, and CAGL0F00181 were implicated in mediating adhesion to C. albicans hyphae and remarkably, their expression was induced by incubation with germinated C. albicans. Thus, we found a near essential requirement for the presence of C. albicans for both initial colonization and establishment of OPC infection by C. glabrata. PMID:27029023

  6. Antibiofilm activity of carboxymethyl chitosan on the biofilms of non-Candida albicans Candida species.

    PubMed

    Tan, Yulong; Leonhard, Matthias; Moser, Doris; Schneider-Stickler, Berit

    2016-09-20

    Although most cases of candidiasis have been attributed to Candida albicans, non-C. albicans Candida species have been isolated in increasing numbers in patients. In this study, we determined the inhibition of carboxymethyl chitosan (CM-chitosan) on single and mixed species biofilm of non-albicans Candida species, including Candida tropicalis, Candida parapsilosis, Candida krusei and Candida glabrata. Biofilm by all tested species in microtiter plates were inhibited nearly 70%. CM-chitosan inhibited mixed species biofilm in microtiter plates and also on medical materials surfaces. To investigate the mechanism, the effect of CM-chitosan on cell viability and biofilm growth was employed. CM-chitosan inhibited Candida planktonic growth as well as adhesion. Further biofilm formation was inhibited with CM-chitosan added at 90min, 12h or 24h after biofilm initiation. CM-chitosan was not only able to inhibit the metabolic activity of Candida cells, but was also active upon the establishment and the development of biofilms. PMID:27261732

  7. Antibiofilm activity of carboxymethyl chitosan on the biofilms of non-Candida albicans Candida species.

    PubMed

    Tan, Yulong; Leonhard, Matthias; Moser, Doris; Schneider-Stickler, Berit

    2016-09-20

    Although most cases of candidiasis have been attributed to Candida albicans, non-C. albicans Candida species have been isolated in increasing numbers in patients. In this study, we determined the inhibition of carboxymethyl chitosan (CM-chitosan) on single and mixed species biofilm of non-albicans Candida species, including Candida tropicalis, Candida parapsilosis, Candida krusei and Candida glabrata. Biofilm by all tested species in microtiter plates were inhibited nearly 70%. CM-chitosan inhibited mixed species biofilm in microtiter plates and also on medical materials surfaces. To investigate the mechanism, the effect of CM-chitosan on cell viability and biofilm growth was employed. CM-chitosan inhibited Candida planktonic growth as well as adhesion. Further biofilm formation was inhibited with CM-chitosan added at 90min, 12h or 24h after biofilm initiation. CM-chitosan was not only able to inhibit the metabolic activity of Candida cells, but was also active upon the establishment and the development of biofilms.

  8. The antimicrobial effects of selenium nanoparticle-enriched probiotics and their fermented broth against Candida albicans

    PubMed Central

    2014-01-01

    Background Lactic acid bacteria are considered important probiotics for prevention of some infections. The aim of this work was to investigate the effect of selenium dioxide on the antifungal activity of Lactobacillus plantarum and L. johnsonii against Candida albicans. Methods Lactobacillus plantarum and L. johnsonii cells, grown in the presence and absence of selenium dioxide, and their cell-free spent culture media were tested for antifungal activity against C. albicans ATCC 14053 by a hole-plate diffusion method and a time-kill assay. Results Both L. plantarum and L. johnsonii reduced selenium dioxide to cell-associated elemental selenium nanoparticles. The cell-free spent culture media, from both Lactobacillus species that had been grown with selenium dioxide for 48 h, showed enhanced antifungal activity against C. albicans. Enhanced antifungal activity of cell biomass against C. albicans was also observed in cultures grown with selenium dioxide. Conclusions Selenium dioxide-treated Lactobacillus spp. or their cell-free spent broth inhibited the growth of C. albicans and should be investigated for possible use in anti-Candida probiotic formulations in future. PMID:24906455

  9. Baicalin prevents Candida albicans infections via increasing its apoptosis rate

    SciTech Connect

    Yang, Shulong; Fu, Yingyuan Wu, Xiuzhen; Zhou, Zhixing; Xu, Jing; Zeng, Xiaoping; Kuang, Nanzhen; Zeng, Yurong

    2014-08-15

    Highlights: • Baicalin increases the ratio of the G0/G1 stages and C. albicans apoptosis. • Baicalin decreases the proliferation index of C. albicans. • Baicalin inhibits the biosynthesis of DNA, RNA and protein in C. albicans. • Baicalin depresses Succinate Dehydrogenase and Ca{sup 2+}–Mg{sup 2+} ATPase in C. albicans. • Baicalin increases the endocytic free Ca{sup 2+} concentration in C. albicans. - Abstract: Background: These experiments were employed to explore the mechanisms underlying baicalin action on Candida albicans. Methodology and principal findings: We detected the baicalin inhibition effects on three isotope-labeled precursors of {sup 3}H-UdR, {sup 3}H-TdR and {sup 3}H-leucine incorporation into C. albicans using the isotope incorporation technology. The activities of Succinate Dehydrogenase (SDH), cytochrome oxidase (CCO) and Ca{sup 2+}–Mg{sup 2+} ATPase, cytosolic Ca{sup 2+} concentration, the cell cycle and apoptosis, as well as the ultrastructure of C.albicans were also tested. We found that baicalin inhibited {sup 3}H-UdR, {sup 3}H-TdR and {sup 3}H-leucine incorporation into C.albicans (P < 0.005). The activities of the SDH and Ca{sup 2+}–Mg{sup 2+} ATPase of C.albicans in baicalin groups were lower than those in control group (P < 0.05). Ca{sup 2+} concentrations of C. albicans in baicalin groups were much higher than those in control group (P < 0.05). The ratio of C.albicans at the G0/G1 stage increased in baicalin groups in dose dependent manner (P < 0.01). There were a significant differences in the apoptosis rate of C.albicans between baicalin and control groups (P < 0.01). After 12–48 h incubation with baicalin (1 mg/ml), C. albicans shown to be markedly damaged under transmission electron micrographs. Innovation and significance: Baicalin can increase the apoptosis rate of C. albicans. These effects of Baicalin may involved in its inhibiting the activities of the SDH and Ca{sup 2+}–Mg{sup 2+} ATPase, increasing

  10. Postantifungal Effect of Micafungin against the Species Complexes of Candida albicans and Candida parapsilosis

    PubMed Central

    Gil-Alonso, Sandra; Jauregizar, Nerea; Eraso, Elena; Quindós, Guillermo

    2015-01-01

    Micafungin is an effective antifungal agent useful for the therapy of invasive candidiasis. Candida albicans is the most common cause of invasive candidiasis; however, infections due to non-C. albicans species, such as Candida parapsilosis, are rising. Killing and postantifungal effects (PAFE) are important factors in both dose interval choice and infection outcome. The aim of this study was to determinate the micafungin PAFE against 7 C. albicans strains, 5 Candida dubliniensis, 2 Candida Africana, 3 C. parapsilosis, 2 Candida metapsilosis and 2 Candida orthopsilosis. For PAFE studies, cells were exposed to micafungin for 1 h at concentrations ranging from 0.12 to 8 μg/ml. Time-kill experiments (TK) were conducted at the same concentrations. Samples were removed at each time point (0-48 h) and viable counts determined. Micafungin (2 μg/ml) was fungicidal (≥ 3 log10 reduction) in TK against 5 out of 14 (36%) strains of C. albicans complex. In PAFE experiments, fungicidal endpoint was achieved against 2 out of 14 strains (14%). In TK against C. parapsilosis, 8 μg/ml of micafungin turned out to be fungicidal against 4 out 7 (57%) strains. Conversely, fungicidal endpoint was not achieved in PAFE studies. PAFE results for C. albicans complex (41.83 ± 2.18 h) differed from C. parapsilosis complex (8.07 ± 4.2 h) at the highest tested concentration of micafungin. In conclusion, micafungin showed significant differences in PAFE against C. albicans and C. parapsilosis complexes, being PAFE for the C. albicans complex longer than for the C. parapsilosis complex. PMID:26168269

  11. Postantifungal Effect of Micafungin against the Species Complexes of Candida albicans and Candida parapsilosis.

    PubMed

    Gil-Alonso, Sandra; Jauregizar, Nerea; Eraso, Elena; Quindós, Guillermo

    2015-01-01

    Micafungin is an effective antifungal agent useful for the therapy of invasive candidiasis. Candida albicans is the most common cause of invasive candidiasis; however, infections due to non-C. albicans species, such as Candida parapsilosis, are rising. Killing and postantifungal effects (PAFE) are important factors in both dose interval choice and infection outcome. The aim of this study was to determinate the micafungin PAFE against 7 C. albicans strains, 5 Candida dubliniensis, 2 Candida Africana, 3 C. parapsilosis, 2 Candida metapsilosis and 2 Candida orthopsilosis. For PAFE studies, cells were exposed to micafungin for 1 h at concentrations ranging from 0.12 to 8 μg/ml. Time-kill experiments (TK) were conducted at the same concentrations. Samples were removed at each time point (0-48 h) and viable counts determined. Micafungin (2 μg/ml) was fungicidal (≥ 3 log10 reduction) in TK against 5 out of 14 (36%) strains of C. albicans complex. In PAFE experiments, fungicidal endpoint was achieved against 2 out of 14 strains (14%). In TK against C. parapsilosis, 8 μg/ml of micafungin turned out to be fungicidal against 4 out 7 (57%) strains. Conversely, fungicidal endpoint was not achieved in PAFE studies. PAFE results for C. albicans complex (41.83 ± 2.18 h) differed from C. parapsilosis complex (8.07 ± 4.2 h) at the highest tested concentration of micafungin. In conclusion, micafungin showed significant differences in PAFE against C. albicans and C. parapsilosis complexes, being PAFE for the C. albicans complex longer than for the C. parapsilosis complex.

  12. Anticandidal action of fungal chitosan against Candida albicans.

    PubMed

    Tayel, Ahmed A; Moussa, Shaaban; el-Tras, Wael F; Knittel, Dierk; Opwis, Klaus; Schollmeyer, Eckhard

    2010-11-01

    The anticandidal activity of four fungal chitosan types, produced from Mucor rouxii DSM-1191, against three Candida albicans strains was determined. The most bioactive chitosan type, to inhibit C. albicans growth, had the lowest molecular weight (32 kDa) and the highest deacetylation degree (94%). Water soluble types had stronger anticandidal activity than soluble types in 1% acetic acid solution. Scanning electron micrographs of treated C. albicans with fungal chitosan proved that chitosan principally interact with yeast cell wall, causing severe swelling and asymmetric rough shapes, and subsequent cell wall lyses with the prolonging of exposure time. Fungal chitosan could be recommended for C. albicans control as a powerful and safe alternative to synthetic and chemical fungicides. PMID:20603144

  13. Rat indwelling urinary catheter model of Candida albicans biofilm infection.

    PubMed

    Nett, Jeniel E; Brooks, Erin G; Cabezas-Olcoz, Jonathan; Sanchez, Hiram; Zarnowski, Robert; Marchillo, Karen; Andes, David R

    2014-12-01

    Indwelling urinary catheters are commonly used in the management of hospitalized patients. Candida can adhere to the device surface and propagate as a biofilm. These Candida biofilm communities differ from free-floating Candida, exhibiting high tolerance to antifungal therapy. The significance of catheter-associated candiduria is often unclear, and treatment may be problematic considering the biofilm drug-resistant phenotype. Here we describe a rodent model for the study of urinary catheter-associated Candida albicans biofilm infection that mimics this common process in patients. In the setting of a functioning, indwelling urinary catheter in a rat, Candida proliferated as a biofilm on the device surface. Characteristic biofilm architecture was observed, including adherent, filamentous cells embedded in an extracellular matrix. Similar to what occurs in human patients, animals with this infection developed candiduria and pyuria. Infection progressed to cystitis, and a biofilmlike covering was observed over the bladder surface. Furthermore, large numbers of C. albicans cells were dispersed into the urine from either the catheter or bladder wall biofilm over the infection period. We successfully utilized the model to test the efficacy of antifungals, analyze transcriptional patterns, and examine the phenotype of a genetic mutant. The model should be useful for future investigations involving the pathogenesis, diagnosis, therapy, prevention, and drug resistance of Candida biofilms in the urinary tract.

  14. Occurrence ofCandida albicans in fresh gull feces in temperate and subtropical areas.

    PubMed

    Buck, J D

    1983-07-01

    The occurrence ofCandida albicans in fresh gull (Larus spp.) feces was compared in temperate and subtropical locations. Of 239 fresh samples, 133 were obtained in southeastern Connecticut and 106 from different sites on the southeastern and central western coasts of Florida. Overall, 60% of all feces containedC. albicans. Of the Connecticut samples, 78% were positive, whereas 38% of the Florida samples revealed the presence of the yeast. Only 1 of 24 samples of fresh brown pelican feces containedC. albicans. Differences inC. albicans occurrence in birds in various locations was ascribed to variations in habitat and feeding behavior. Samples of water from a municipal reservoir in Connecticut were routinely positive, with an average cell density of 20/liter. Two fresh gull samples obtained on the reservoir bank containedC. albicans at an average cell concentration of 5, 200/g. The frequency ofC. albicans in gull droppings was higher than reported by others, and the yeast is common in temperate waters. These findings have important public health implications. PMID:24221652

  15. In vitro activity of eugenol against Candida albicans biofilms.

    PubMed

    He, Miao; Du, Minquan; Fan, Mingwen; Bian, Zhuan

    2007-03-01

    Most manifestations of candidiasis are associated with biofilm formation occurring on the surfaces of host tissues and medical devices. Candida albicans is the most frequently isolated causative pathogen of candidiasis, and the biofilms display significantly increased levels of resistance to the conventional antifungal agents. Eugenol, the major phenolic component of clove essential oil, possesses potent antifungal activity. The aim of this study was to investigate the effects of eugenol on preformed biofilms, adherent cells, subsequent biofilm formation and cell morphogenesis of C. albicans. Eugenol displayed in vitro activity against C. albicans cells within biofilms, when MIC(50) for sessile cells was 500 mg/L. C. albicans adherent cell populations (after 0, 1, 2 and 4 h of adherence) were treated with various concentrations of eugenol (0, 20, 200 and 2,000 mg/L). The extent of subsequent biofilm formation were then assessed with the tetrazolium salt reduction assay. Effect of eugenol on morphogenesis of C. albicans cells was observed by scanning electron microscopy (SEM). The results indicated that the effect of eugenol on adherent cells and subsequent biofilm formation was dependent on the initial adherence time and the concentration of this compound, and that eugenol can inhibit filamentous growth of C. albicans cells. In addition, using human erythrocytes, eugenol showed low hemolytic activity. These results indicated that eugenol displayed potent activity against C. albicans biofilms in vitro with low cytotoxicity and therefore has potential therapeutic implication for biofilm-associated candidal infections. PMID:17356790

  16. Survival of Candida albicans in tropical marine and fresh waters.

    PubMed Central

    Valdes-Collazo, L; Schultz, A J; Hazen, T C

    1987-01-01

    A survey of Candida albicans indicated that the organism was present at all sites sampled in a rain forest stream and in near-shore coastal waters of Puerto Rico. In the rain forest watershed no relationship existed between densities of fecal coliforms and densities of C. albicans. At two pristine sites in the rain forest watershed both C. albicans and Escherichia coli survived in diffusion chambers for extended periods of time. In near-shore coastal waters C. albicans and E. coli survival times in diffusion chambers were enhanced by effluent from a rum distillery. The rum distillery effluent had a greater effect on E. coli than on C. albicans survival in the diffusion chambers. These studies show that neither E. coli nor C. albicans organisms are good indicators of recent fecal contamination in tropical waters. It further demonstrates that pristine freshwater environments and marine waters receiving organic loading in the tropics can support densities of C. albicans which may be a health hazard. Images PMID:3310885

  17. Comparison of the hemolytic activity between C. albicans and non-albicans Candida species.

    PubMed

    Rossoni, Rodnei Dennis; Barbosa, Júnia Oliveira; Vilela, Simone Furgeri Godinho; Jorge, Antonio Olavo Cardoso; Junqueira, Juliana Campos

    2013-01-01

    The ability to produce enzymes, such as hemolysins, is an important virulence factor for the genus Candida.The objective of this study was to compare the hemolytic activity between C. albicansand non-albicans Candida species. Fifty strains of Candida species, isolated from the oral cavity of patients infected with HIV were studied. The isolates included the following species: C. albicans, C. dubliniensis, C. glabrata, C. tropicalis, C. krusei, C. parapsilosis, C. dubliniensis, C. norvegensis, C. lusitaniae, and C. guilliermondii. Hemolysin production was evaluated on Sabouraud dextrose agar containing chloramphenicol, blood, and glucose. A loop-full of pure Candidaculture was spot-inoculated onto plates and incubated at 37 ºC for 24 h in a 5% CO2 atmosphere. Hemolytic activity was defined as the formation of a translucent halo around the colonies. All C. albicansstrains that were studied produced hemolysins. Among the non-albicans Candidaspecies, 86% exhibited hemolytic activity. Only C. guilliermondiiand some C. parapsilosis isolates were negative for this enzyme. In conclusion, most non-albicans Candidaspecies had a similar ability to produce hemolysins when compared to C. albicans.

  18. Effect of Marine Polyunsaturated Fatty Acids on Biofilm Formation of Candida albicans and Candida dubliniensis

    PubMed Central

    Thibane, Vuyisile S.; Kock, Johan L. F.; Ells, Ruan; van Wyk, Pieter W. J.; Pohl, Carolina H.

    2010-01-01

    The effect of marine polyunsaturated fatty acids on biofilm formation by the human pathogens Candida albicans and Candida dubliniensis was investigated. It was found that stearidonic acid (18:4 n-3), eicosapentaenoic acid (20:5 n-3), docosapentaenoic acid (22:5 n-3) and docosahexaenoic acid (22:6 n-3) have an inhibitory effect on mitochondrial metabolism of both C. albicans and C. dubliniensis and that the production of biofilm biomass by C. dubliniensis was more susceptible to these fatty acids than C. albicans. Ultrastructural differences, which may be due to increased oxidative stress, were observed between treated and untreated cells of C. albicans and C. dubliniensis with formation of rough cell walls by both species and fibrillar structures in C. dubliniensis. These results indicate that marine polyunsaturated fatty acids may be useful in the treatment and/or prevention of biofilms formed by these pathogenic yeasts. PMID:21116408

  19. Candida albicans specializations for iron homeostasis: from commensalism to virulence.

    PubMed

    Noble, Suzanne M

    2013-12-01

    Candida albicans is a fungal commensal-pathogen that persistently associates with its mammalian hosts. Between the commensal and pathogenic lifestyles, this microorganism inhabits host niches that differ markedly in the levels of bioavailable iron. A number of recent studies have exposed C. albicans specializations for acquiring iron from specific host molecules in regions where iron is scarce, while also defending against iron-related toxicity in regions where iron occurs in surfeit. Together, these results point to a central role for iron homeostasis in the evolution of this important human pathogen.

  20. Vinegar as an antimicrobial agent for control of Candida spp. in complete denture wearers.

    PubMed

    Pinto, Telma Maria Silva; Neves, Ana Christina Claro; Leão, Mariella Vieira Pereira; Jorge, Antonio Olavo Cardoso

    2008-01-01

    The use of denture is known to increase the carriage of Candida in healthy patients, and the proliferation of Candida albicans strains can be associated with denture-induced stomatitis. The aim of this study was to evaluate the use of vinegar as an antimicrobial agent for control of Candida spp. in complete upper denture wearers. Fifty-five patients were submitted to a detailed clinical interview and oral clinical examination, and were instructed to keep their dentures immersed in a 10% vinegar solution (pH less than 3) overnight for 45 days. Before and after the experimental period, saliva samples were collected for detection of Candida, counting of cfu/mL and identification of species by phenotypical tests (germ tube formation, chlamidoconidia production, and carbohydrate fermentation and assimilation). The results were analyzed using Spearman's correlation and Student's t-test (pCandida yeasts were present in 87.3% of saliva samples before the treatment. A significant reduction was verified in CFU/mL counts of Candida after treatment. A positive correlation between Candida and denture stomatitis was verified, since the decrease of cfu/mL counts was correlated with a reduction in cases of denture stomatitis. Although it was not able to eliminate C. albicans, the immersion of the complete denture in 10% vinegar solution, during the night, reduced the amounts (cfu/mL) of Candida spp. in the saliva and the presence of denture stomatitis in the studied patients. PMID:19082396

  1. Effect of serum and surface characteristics on Candida albicans biofilm formation.

    PubMed

    Frade, João Pedro; Arthington-Skaggs, Beth A

    2011-07-01

    Candida spp. biofilms can be established on a wide range of materials, including implanted medical devices, and can display a resistant phenotype to antifungal drugs. Several factors, including host and surface properties, may influence the establishment and the development of Candida albicans biofilms on biotic and abiotic surfaces. We therefore selected a collection of C. albicans clinical isolates to evaluate the effect of surface and serum on biofilm attachment and development. Disc coupons from the CDC biofilm reactor were used in a well plate assay to study biofilm production on six different surfaces with or without the addition of serum: polycarbonate, polystyrene, stainless steel, Teflon, polyvinyl chloride or hydroxyapatite. Our results showed that serum increases in vitro C. albicans biofilm formation on a wide range of distinct surfaces including metallic and non-metallic materials, and that roughness and hydrophobicity can modulate C. albicans biofilm formation. These findings were also confirmed by scanning electron microscopy and it revealed the deposition of extracellular material on hyphae attached to a solid surface. Interestingly, adhesion can be significantly increased in the early stages of colonisation when serum is provided as a conditioning film in a surface-dependent manner.

  2. Antifungal Activity of Cinnamon Oil and Olive Oil against Candida Spp. Isolated from Blood Stream Infections

    PubMed Central

    Rohilla, Hina; Singh, Gajender; Punia, Parul

    2016-01-01

    Introduction Recently non-albicans Candida has emerged as a major cause of morbidity and mortality in blood stream infections. Some species of the Candida are becoming increasingly resistant to first line and second line antifungals such as echinocandins and fluconazole. In view of increasing global antifungal resistance, role of alternative and better antifungals like natural plant products need to be explored. Essential oils are known to exhibit antimicrobial activity against various fungi. Hence, we evaluated the efficacy of cinnamon oil and olive oil against Candida spp. Aim To evaluate the invitro antifungal activity of olive oil and cinnamon oil against blood stream Candida isolates. Materials and Methods The present prospective observational study was conducted in the Department of Microbiology at a tertiary care teaching hospital during one year June 2011-July 2012. Blood samples were collected from 1376 patients clinically suspected to have fungal septicaemia, out of which 100 (7.2%) Candida isolates obtained, were speciated by conventional methods. Antifungal susceptibility testing of all the isolates was done against fluconazole, voriconazole as per NCCL (M27-A2) and against olive oil and cinnamon oil by agar well diffusion method. Results Prevalence of Candidemia was 7.26%. C. albicans (85.3%) and C. parapsilosis (85.7%) were most sensitive to fluconazole followed by C. tropicalis (67.4%). All isolates were 100% sensitive to voriconazole. Both oils were found to be effective against nearly 50% of the Candida isolates. About 55.5% of fluconazole resistant C. krusei strains were sensitive to olive and cinnamon oil. Conclusion Fluconazole resistant non-albicans Candida has emerged as major cause of Candidemia. Cinnamon and olive oil show marked sensitivity against albicans and non-albicans spp. PMID:27656437

  3. Design and Evaluation of Peptide Nucleic Acid Probes for Specific Identification of Candida albicans

    PubMed Central

    Kim, Hyun-Joong

    2014-01-01

    Candida albicans is an important cause of systemic fungal infections, and rapid diagnostics for identifying and differentiating C. albicans from other Candida species are critical for the timely application of appropriate antimicrobial therapy, improved patient outcomes, and pharmaceutical cost savings. In this work, two 28S rRNA-directed peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH) probes, P-Ca726 (targeting a novel region of the ribosome) and P-CalB2208 (targeting a previously reported region), were evaluated. Hybridization conditions were optimized by using both fluorescence microscopy (FM) and flow cytometry (FCM), and probes were screened for specificity and discriminative ability against a panel of C. albicans and various nontarget Candida spp. The performance of these PNA probes was compared quantitatively against that of DNA probes or DNA probe/helper combinations directed against the same target regions. Ratiometric analyses of FCM results indicated that both the hybridization quality and yield of the PNA probes were higher than those of the DNA probes. In FCM-based comparisons of the PNA probes, P-Ca726 was found to be highly specific, showing 2.5- to 5.5-fold-higher discriminatory power for C. albicans than P-CalB2208. The use of formamide further improved the performance of the new probe. Our results reinforce the significant practical and diagnostic advantages of PNA probes over their DNA counterparts for FISH and indicate that P-Ca726 may be used advantageously for the rapid and specific identification of C. albicans in clinical and related applications, especially when combined with FCM. PMID:25428160

  4. Phenotypic consequences of LYS4 gene disruption in Candida albicans.

    PubMed

    Gabriel, Iwona; Kur, Krzysztof; Laforce-Nesbitt, Sonia S; Pulickal, Anoop S; Bliss, Joseph M; Milewski, Sławomir

    2014-08-01

    A BLAST search of the Candida Genome Database with the Saccharomyces cerevisiae LYS4 sequence known to encode homoaconitase (HA) revealed ORFs 19.3846 and 19.11327. Both alleles of the LYS4 gene were sequentially disrupted in Candida albicans BWP17 cells using PCR-based methodology. The null lys4Δ mutant exhibited lysine auxotrophy in minimal medium but was able to grow in the presence of l-Lys and α-aminoadipate, an intermediate of the α-aminoadipate pathway, at millimolar concentrations. The presence of d-Lys and pipecolic acid did not trigger lys4Δ growth. The C. albicans lys4Δ mutant cells demonstrated diminished germination ability. However, their virulence in vivo in a murine model of disseminated neonatal candidiasis appeared identical to that of the wild-type strain. Moreover, there was no statistically significant difference in fungal burden of infected tissues between the strains.

  5. Effect of tunicamycin on Candida albicans biofilm formation and maintenance

    PubMed Central

    Pierce, Christopher G.; Thomas, Derek P.; López-Ribot, José L.

    2009-01-01

    Background Candida albicans is a common opportunistic pathogen of the human body and is the frequent causative agent of candidiasis. Typically, these infections are associated with the formation of biofilms on both host tissues and implanted biomaterials. As a result of the intrinsic resistance of C. albicans biofilms to most antifungal agents, new strategies are needed to combat these infections. Methods Here we have used a 96-well microtitre plate model of C. albicans biofilm formation to study the inhibitory effect of tunicamycin, a nucleoside antibiotic that inhibits N-linked glycosylation affecting cell wall and secreted proteins, on C. albicans biofilm formation. A proteomic approach was used to study the effect of tunicamycin on levels of glycosylation of key secreted mannoproteins in the biofilm matrix. Results Our results revealed that physiological concentrations of tunicamycin displayed significant inhibitory effects on biofilm development and maintenance, while not affecting overall cell growth or morphology. However, tunicamycin exerted a minimal effect on fully mature, pre-formed C. albicans biofilms. Conclusions The effect of tunicamycin on the C. albicans biofilm mode of growth demonstrates the importance of N-linked glycosylation in the developmental stages of biofilm formation. In addition, our results indicate that N-linked glycosylation represents an attractive target for the development of alternative strategies for the prevention of biofilm formation by this important pathogenic fungus. PMID:19098294

  6. Anti-biofilm Properties of Peganum harmala against Candida albicans

    PubMed Central

    Aboualigalehdari, Elham; Sadeghifard, Nourkhoda; Taherikalani, Morovat; Zargoush, Zaynab; Tahmasebi, Zahra; Badakhsh, Behzad; Rostamzad, Arman; Ghafourian, Sobhan; Pakzad, Iraj

    2016-01-01

    Objectives Vaginitis still remains as a health issue in women. It is notable that Candida albicans producing biofilm is considered a microorganism responsible for vaginitis with hard to treat. Also, Peganum harmala was applied as an anti fungal in treatment for many infections in Iran. Therefore, this study goal to investigate the role of P. harmala in inhibition of biofilm formation in C. albicans. Methods So, 27 C. albicans collected from women with Vaginitis, then subjected for biofilm formation assay. P. harmala was applied as antibiofilm formation in C. albicans. Results Our results demonstrated that P. harmala in concentration of 12 μg/ml easily inhibited strong biofilm formation; while the concentrations of 10 and 6 μg/ml inhibited biofilm formation in moderate and weak biofilm formation C. albicans strains, respectively. Conclusion Hence, the current study presented P. harmala as antibiofilm herbal medicine for C. albicans; but in vivo study suggested to be performed to confirm its effectiveness. PMID:27169010

  7. Oxidative stress of photodynamic antimicrobial chemotherapy inhibits Candida albicans virulence

    NASA Astrophysics Data System (ADS)

    Kato, Ilka Tiemy; Prates, Renato Araujo; Tegos, George P.; Hamblin, Michael R.; Simões Ribeiro, Martha

    2011-03-01

    Photodynamic antimicrobial chemotherapy (PACT) is based on the principal that microorganisms will be inactivated using a light source combined to a photosensitizing agent in the presence of oxygen. Oxidative damage of cell components occurs by the action of reactive oxygen species leading to cell death for microbial species. It has been demonstrated that PACT is highly efficient in vitro against a wide range of pathogens, however, there is limited information for its in vivo potential. In addition, it has been demonstrated that sublethal photodynamic inactivation may alter the virulence determinants of microorganisms. In this study, we explored the effect of sublethal photodynamic inactivation to the virulence factors of Candida albicans. Methylene Blue (MB) was used as photosensitizer for sublethal photodynamic challenge on C. albicans associated with a diode laser irradiation (λ=660nm). The parameters of irradiation were selected in causing no reduction of viable cells. The potential effects of PACT on virulence determinants of C. albicans cells were investigated by analysis of germ tube formation and in vivo pathogenicity assays. Systemic infection was induced in mice by the injection of fungal suspension in the lateral caudal vein. C. albicans exposed to sublethal photodynamic inactivation formed significantly less germ tube than untreated cells. In addition, mice infected with C. albicans submitted to sublethal PACT survived for a longer period of time than mice infected with untreated cells. The oxidative damage promoted by sublethal photodynamic inactivation inhibited virulence determinants and reduced in vivo pathogenicity of C. albicans.

  8. Dental caries in rats associated with Candida albicans.

    PubMed

    Klinke, T; Guggenheim, B; Klimm, W; Thurnheer, T

    2011-01-01

    In addition to occasional opportunistic colonization of the oral mucosa, Candida albicans is frequently found in carious dentin. The yeast's potential to induce dental caries as a consequence of its pronounced ability to produce and tolerate acids was investigated. Eighty caries-active Osborne-Mendel rats were raised on an ampicillin-supplemented diet and exposed to C. albicans and/or Streptococcus mutans, except for controls. Throughout the 28-day test period, the animals were offered the modified cariogenic diet 2000a, containing 40% various sugars. Subsequently, maxillary molars were scored for plaque extent. After dissection, the mandibular molars were evaluated for smooth surface and fissure caries. Test animals exposed to C. albicans displayed considerably more advanced fissure lesions (p < 0.001) than non-exposed controls. While S. mutans yielded similar results, a combined association of C. albicans and S. mutans had no effect on occlusal caries incidence. Substituting dietary sucrose by glucose did not modify caries induction by C. albicans. However, animals fed a diet containing 20% of both sugars showed no differences to non-infected controls. Smooth surface caries was not generated by the yeast. This study provides experimental evidence that C. albicans is capable of causing occlusal caries in rats at a high rate.

  9. [Progress on the role of Toll-like receptors in Candida albicans infections].

    PubMed

    Yun, Zhou; Jianping, Pan

    2016-05-25

    Toll like receptors (TLRs) are expressed mainly on innate immunocytes such as dendritic cells and macrophages, and may have the potential to recognize and bind to pathogen-associated molecular patterns (PAMPs) from Candida albicans, thereby triggering the downstream signals. The genetic polymorphism of TLRs is associated with susceptibility to Candida albicans. The activation of TLRs by PAMPs from Candida albicans can induce the production of proinflammatory cytokines that play key roles in the anti-infection of Candida albicans. However, in order to evade the immune response of host,Candida albicans can also change its bacterial phase. Understanding of the interaction between TLRs and Candida albicans will provide novel evidence to further clarify the mechanisms of anti-fungal immune response. PMID:27651197

  10. Biotyping of Candida albicans: results of an international collaborative survey.

    PubMed Central

    Odds, F C; Auger, P; Krogh, P; Neely, A N; Segal, E

    1989-01-01

    An agar plate system for biotyping isolates of Candida albicans was evaluated in four laboratories for 18 coded yeast isolates, each tested in triplicate on duplicate series of agar plates. The results showed that the biotyping system gave excellent intralaboratory reproducibility. However, because the concordance of data among laboratories was poor, the method must be regarded as suitable only for research applications and not for routine use. PMID:2671015

  11. Candida albicans and Enterococcus faecalis in the gut

    PubMed Central

    Garsin, Danielle A; Lorenz, Michael C

    2013-01-01

    The fungus Candida albicans and the gram-positive bacterium Enterococcus faecalis are both normal residents of the human gut microbiome and cause opportunistic disseminated infections in immunocompromised individuals. Using a nematode infection model, we recently showed that co-infection resulted in less pathology and less mortality than infection with either species alone and this was partly explained by an interkingdom signaling event in which a bacterial-derived product inhibits hyphal morphogenesis of C. albicans. In this addendum we discuss these findings in the contest of other described bacterial-fungal interactions and recent data suggesting a potentially synergistic relationship between these two species in the mouse gut as well. We suggest that E. faecalis and C. albicans promote a mutually beneficial association with the host, in effect choosing a commensal lifestyle over a pathogenic one. PMID:23941906

  12. Candida albicans mutant construction and characterization of selected virulence determinants.

    PubMed

    Motaung, T E; Albertyn, J; Pohl, C H; Köhler, Gerwald

    2015-08-01

    Candida albicans is a diploid, polymorphic yeast, associated with humans, where it mostly causes no harm. However, under certain conditions it can cause infections ranging from superficial to life threatening. This ability to become pathogenic is often linked to the immune status of the host as well as the expression of certain virulence factors by the yeast. Due to the importance of C. albicans as a pathogen, determination of the molecular mechanisms that allow this yeast to cause disease is important. These studies rely on the ability of researchers to create deletion mutants of specific genes in order to study their function. This article provides a critical review of the important techniques used to create deletion mutants in C. albicans and highlights how these deletion mutants can be used to determine the role of genes in the expression of virulence factors in vitro.

  13. Ocimum sanctum essential oil inhibits virulence attributes in Candida albicans.

    PubMed

    Khan, Amber; Ahmad, Aijaz; Xess, Immaculata; Khan, Luqman A; Manzoor, Nikhat

    2014-03-15

    Candida albicans is an opportunistic human fungal pathogen which causes disease mainly in immunocompromised patients. Activity of hydrolytic enzymes is essential for virulence of C. albicans and so is the capacity of these cells to undergo transition from yeast to mycelial form of growth. Ocimum sanctum is cultivated worldwide for its essential oil which exhibits medicinal properties. This work evaluates the anti-virulence activity of O. sanctum essential oil (OSEO) on 22 strains of C. albicans (including a standard strain ATCC 90028) isolated from both HIV positive and HIV negative patients. Candida isolates were exposed to sub-MICs of OSEO. In vitro secretion of proteinases and phospholipases was evaluated by plate assay containing BSA and egg yolk respectively. Morphological transition from yeast to filamentous form was monitored microscopically in LSM. For genetic analysis, respective genes associated with morphological transition (HWP1), proteinase (SAP1) and phospholipase (PLB2) were also investigated by Real Time PCR (qRT-PCR). Results were analyzed using Student's t-test. OSEO inhibits morphological transition in C. albicans and had a significant inhibitory effect on extracellular secretion of proteinases and phospholipases. Expression profile of respective selected genes associated with C. albicans virulence by qRT-PCR showed a reduced expression of HWP1, SAP1 and PLB2 genes in cells treated with sub-inhibitory concentrations of OSEO. This work suggests that OSEO inhibits morphological transition in C. albicans and decreases the secretion of hydrolytic enzymes involved in the early stage of infection as well as down regulates the associated genes. Further studies will assess the clinical application of OSEO and its constituents in the treatment of fungal infections. PMID:24252340

  14. Baicalein induces programmed cell death in Candida albicans.

    PubMed

    Dai, Bao-Di; Cao, Ying-Ying; Huang, Shan; Xu, Yong-Gang; Gao, Ping-Hui; Wang, Yan; Jiang, Yuan-Ying

    2009-08-01

    Recent evidence has revealed the occurrence of an apoptotic phenotype in Candida albicans that is inducible with environmental stresses such as acetic acid, hydrogen peroxide, and amphotericin B. In the present study, we found that the Chinese herbal medicine Baicalein (BE), which was one of the skullcapflavones, can induce apoptosis in C. albicans. The apoptotic effects of BE were detected by flow cytometry using Annexin V-FITC and DAPI, and it was confirmed by transmission electron microscopy analysis. After exposure to 4 microg/ml BE for 12 h, about 10% of C. albicans cells were apoptotic. Both the increasing intracellular levels of reactive oxygen species (ROS) and upregulation of some redox-related genes (CAP1, SOD2, TRR1) were observed. Furthermore, we compared the survivals of CAP1 deleted, wild-type, and overexpressed strains and found that Cap1p attenuated BE-initiated cell death, which was coherent with a higher mRNA level of the CAP1 gene. In addition, the mitochondrial membrane potential of C. albicans cells changed significantly ( p<0.001) upon BE treatment compared with control. Taken together, our results indicate that BE treatment induces apoptosis in C.albicans cells, and the apoptosis was associated with the breakdown of mitochondrial membrane potential. PMID:19734718

  15. Oxidative stress responses in the human fungal pathogen, Candida albicans.

    PubMed

    Dantas, Alessandra da Silva; Day, Alison; Ikeh, Mélanie; Kos, Iaroslava; Achan, Beatrice; Quinn, Janet

    2015-01-01

    Candida albicans is a major fungal pathogen of humans, causing approximately 400,000 life-threatening systemic infections world-wide each year in severely immunocompromised patients. An important fungicidal mechanism employed by innate immune cells involves the generation of toxic reactive oxygen species (ROS), such as superoxide and hydrogen peroxide. Consequently, there is much interest in the strategies employed by C. albicans to evade the oxidative killing by macrophages and neutrophils. Our understanding of how C. albicans senses and responds to ROS has significantly increased in recent years. Key findings include the observations that hydrogen peroxide triggers the filamentation of this polymorphic fungus and that a superoxide dismutase enzyme with a novel mode of action is expressed at the cell surface of C. albicans. Furthermore, recent studies have indicated that combinations of the chemical stresses generated by phagocytes can actively prevent C. albicans oxidative stress responses through a mechanism termed the stress pathway interference. In this review, we present an up-date of our current understanding of the role and regulation of oxidative stress responses in this important human fungal pathogen. PMID:25723552

  16. Oxidative Stress Responses in the Human Fungal Pathogen, Candida albicans

    PubMed Central

    da Silva Dantas, Alessandra; Day, Alison; Ikeh, Mélanie; Kos, Iaroslava; Achan, Beatrice; Quinn, Janet

    2015-01-01

    Candida albicans is a major fungal pathogen of humans, causing approximately 400,000 life-threatening systemic infections world-wide each year in severely immunocompromised patients. An important fungicidal mechanism employed by innate immune cells involves the generation of toxic reactive oxygen species (ROS), such as superoxide and hydrogen peroxide. Consequently, there is much interest in the strategies employed by C. albicans to evade the oxidative killing by macrophages and neutrophils. Our understanding of how C. albicans senses and responds to ROS has significantly increased in recent years. Key findings include the observations that hydrogen peroxide triggers the filamentation of this polymorphic fungus and that a superoxide dismutase enzyme with a novel mode of action is expressed at the cell surface of C. albicans. Furthermore, recent studies have indicated that combinations of the chemical stresses generated by phagocytes can actively prevent C. albicans oxidative stress responses through a mechanism termed the stress pathway interference. In this review, we present an up-date of our current understanding of the role and regulation of oxidative stress responses in this important human fungal pathogen. PMID:25723552

  17. The genetic basis of fluconazole resistance development in Candida albicans.

    PubMed

    Morschhäuser, Joachim

    2002-07-18

    Infections by the opportunistic fungal pathogen Candida albicans are widely treated with the antifungal agent fluconazole that inhibits the biosynthesis of ergosterol, the major sterol in the fungal plasma membrane. The emergence of fluconazole-resistant C. albicans strains is a significant problem after long-term treatment of recurrent oropharyngeal candidiasis (OPC) in acquired immunodeficiency syndrome (AIDS) patients. Resistance can be caused by alterations in sterol biosynthesis, by mutations in the drug target enzyme, sterol 14alpha-demethylase (14DM), which lower its affinity for fluconazole, by increased expression of the ERG11 gene encoding 14DM, or by overexpression of genes coding for membrane transport proteins of the ABC transporter (CDR1/CDR2) or the major facilitator (MDR1) superfamilies. Different mechanisms are frequently combined to result in a stepwise development of fluconazole resistance over time. The MDR1 gene is not or barely transcribed during growth in vitro in fluconazole-susceptible C. albicans strains, but overexpressed in many fluconazole-resistant clinical isolates, resulting in reduced intracellular fluconazole accumulation. The activation of the gene in resistant isolates is caused by mutations in as yet unknown trans-regulatory factors, and the resulting constitutive high level of MDR1 expression causes resistance to other toxic compounds in addition to fluconazole. Disruption of both alleles of the MDR1 gene in resistant C. albicans isolates abolishes their resistance to these drugs, providing genetic evidence that MDR1 mediates multidrug resistance in C. albicans. PMID:12084466

  18. A Photonic Crystal Protein Hydrogel Sensor for Candida albicans.

    PubMed

    Cai, Zhongyu; Kwak, Daniel H; Punihaole, David; Hong, Zhenmin; Velankar, Sachin S; Liu, Xinyu; Asher, Sanford A

    2015-10-26

    We report two-dimensional (2D) photonic crystal (PC) sensing materials that selectively detect Candida albicans (C. albicans). These sensors utilize Concanavalin A (Con A) protein hydrogels with a 2D PC embedded on the Con A protein hydrogel surface, that multivalently and selectively bind to mannan on the C. albicans cell surface to form crosslinks. The resulting crosslinks shrink the Con A protein hydrogel, reduce the 2D PC particle spacing, and blue-shift the light diffracted from the PC. The diffraction shifts can be visually monitored, measured with a spectrometer, or determined from the Debye diffraction ring diameter. Our unoptimized hydrogel sensor has a detection limit of around 32 CFU/mL for C. albicans. This sensor distinguishes between C. albicans and those microbes devoid of cell-surface mannan such as the gram-negative bacterium E. coli. This sensor provides a proof-of-concept for utilizing recognition between lectins and microbial cell surface carbohydrates to detect microorganisms in aqueous environments. PMID:26480336

  19. Spaceflight enhances cell aggregation and random budding in Candida albicans.

    PubMed

    Crabbé, Aurélie; Nielsen-Preiss, Sheila M; Woolley, Christine M; Barrila, Jennifer; Buchanan, Kent; McCracken, James; Inglis, Diane O; Searles, Stephen C; Nelman-Gonzalez, Mayra A; Ott, C Mark; Wilson, James W; Pierson, Duane L; Stefanyshyn-Piper, Heidemarie M; Hyman, Linda E; Nickerson, Cheryl A

    2013-01-01

    This study presents the first global transcriptional profiling and phenotypic characterization of the major human opportunistic fungal pathogen, Candida albicans, grown in spaceflight conditions. Microarray analysis revealed that C. albicans subjected to short-term spaceflight culture differentially regulated 452 genes compared to synchronous ground controls, which represented 8.3% of the analyzed ORFs. Spaceflight-cultured C. albicans-induced genes involved in cell aggregation (similar to flocculation), which was validated by microscopic and flow cytometry analysis. We also observed enhanced random budding of spaceflight-cultured cells as opposed to bipolar budding patterns for ground samples, in accordance with the gene expression data. Furthermore, genes involved in antifungal agent and stress resistance were differentially regulated in spaceflight, including induction of ABC transporters and members of the major facilitator family, downregulation of ergosterol-encoding genes, and upregulation of genes involved in oxidative stress resistance. Finally, downregulation of genes involved in actin cytoskeleton was observed. Interestingly, the transcriptional regulator Cap1 and over 30% of the Cap1 regulon was differentially expressed in spaceflight-cultured C. albicans. A potential role for Cap1 in the spaceflight response of C. albicans is suggested, as this regulator is involved in random budding, cell aggregation, and oxidative stress resistance; all related to observed spaceflight-associated changes of C. albicans. While culture of C. albicans in microgravity potentiates a global change in gene expression that could induce a virulence-related phenotype, no increased virulence in a murine intraperitoneal (i.p.) infection model was observed under the conditions of this study. Collectively, our data represent an important basis for the assessment of the risk that commensal flora could play during human spaceflight missions. Furthermore, since the low fluid

  20. Cellular Components Mediating Coadherence of Candida albicans and Fusobacterium nucleatum.

    PubMed

    Wu, T; Cen, L; Kaplan, C; Zhou, X; Lux, R; Shi, W; He, X

    2015-10-01

    Candida albicans is an opportunistic fungal pathogen found as part of the normal oral flora. It can be coisolated with Fusobacterium nucleatum, an opportunistic bacterial pathogen, from oral disease sites, such as those involved in refractory periodontitis and pulp necrosis. The physical coadherence between these 2 clinically important microbes has been well documented and suggested to play a role in facilitating their oral colonization and colocalization and contributing to polymicrobial pathogenesis. Previous studies indicated that the physical interaction between C. albicans and F. nucleatum was mediated by the carbohydrate components on the surface of C. albicans and the protein components on the Fusobaterium cell surface. However, the identities of the components involved still remain elusive. This study was aimed at identifying the genetic determinants involved in coaggregation between the 2 species. By screening a C. albicans SN152 mutant library and a panel of F. nucleatum 23726 outer membrane protein mutants, we identified FLO9, which encodes a putative adhesin-like cell wall mannoprotein of C. albicans and radD, an arginine-inhibitable adhesin-encoding gene in F. nucleatum that is involved in interspecies coadherence. Consistent with these findings, we demonstrated that the strong coaggregation between wild-type F. nucleatum 23726 and C. albicans SN152 in an in vitro assay could be greatly inhibited by arginine and mannose. Our study also suggested a complex multifaceted mechanism underlying physical interaction between C. albicans and F. nucleatum and for the first time revealed the identity of major genetic components involved in mediating the coaggregation. These observations provide useful knowledge for developing new targeted treatments for disrupting interactions between these 2 clinically relevant pathogens.

  1. Cellular Components Mediating Coadherence of Candida albicans and Fusobacterium nucleatum

    PubMed Central

    Wu, T.; Cen, L.; Kaplan, C.; Zhou, X.; Lux, R.; Shi, W.; He, X.

    2015-01-01

    Candida albicans is an opportunistic fungal pathogen found as part of the normal oral flora. It can be coisolated with Fusobacterium nucleatum, an opportunistic bacterial pathogen, from oral disease sites, such as those involved in refractory periodontitis and pulp necrosis. The physical coadherence between these 2 clinically important microbes has been well documented and suggested to play a role in facilitating their oral colonization and colocalization and contributing to polymicrobial pathogenesis. Previous studies indicated that the physical interaction between C. albicans and F. nucleatum was mediated by the carbohydrate components on the surface of C. albicans and the protein components on the Fusobaterium cell surface. However, the identities of the components involved still remain elusive. This study was aimed at identifying the genetic determinants involved in coaggregation between the 2 species. By screening a C. albicans SN152 mutant library and a panel of F. nucleatum 23726 outer membrane protein mutants, we identified FLO9, which encodes a putative adhesin-like cell wall mannoprotein of C. albicans and radD, an arginine-inhibitable adhesin-encoding gene in F. nucleatum that is involved in interspecies coadherence. Consistent with these findings, we demonstrated that the strong coaggregation between wild-type F. nucleatum 23726 and C. albicans SN152 in an in vitro assay could be greatly inhibited by arginine and mannose. Our study also suggested a complex multifaceted mechanism underlying physical interaction between C. albicans and F. nucleatum and for the first time revealed the identity of major genetic components involved in mediating the coaggregation. These observations provide useful knowledge for developing new targeted treatments for disrupting interactions between these 2 clinically relevant pathogens. PMID:26152186

  2. Selective photoinactivation of Candida albicans in the non-vertebrate host infection model Galleria mellonella

    PubMed Central

    2013-01-01

    Background Candida spp. are recognized as a primary agent of severe fungal infection in immunocompromised patients, and are the fourth most common cause of bloodstream infections. Our study explores treatment with photodynamic therapy (PDT) as an innovative antimicrobial technology that employs a nontoxic dye, termed a photosensitizer (PS), followed by irradiation with harmless visible light. After photoactivation, the PS produces either singlet oxygen or other reactive oxygen species (ROS) that primarily react with the pathogen cell wall, promoting permeabilization of the membrane and cell death. The emergence of antifungal-resistant Candida strains has motivated the study of antimicrobial PDT (aPDT) as an alternative treatment of these infections. We employed the invertebrate wax moth Galleria mellonella as an in vivo model to study the effects of aPDT against C. albicans infection. The effects of aPDT combined with conventional antifungal drugs were also evaluated in G. mellonella. Results We verified that methylene blue-mediated aPDT prolonged the survival of C. albicans infected G. mellonella larvae. The fungal burden of G. mellonella hemolymph was reduced after aPDT in infected larvae. A fluconazole-resistant C. albicans strain was used to test the combination of aPDT and fluconazole. Administration of fluconazole either before or after exposing the larvae to aPDT significantly prolonged the survival of the larvae compared to either treatment alone. Conclusions G. mellonella is a useful in vivo model to evaluate aPDT as a treatment regimen for Candida infections. The data suggests that combined aPDT and antifungal therapy could be an alternative approach to antifungal-resistant Candida strains. PMID:24083556

  3. Polyketide Glycosides from Bionectria ochroleuca Inhibit Candida albicans Biofilm Formation

    PubMed Central

    2015-01-01

    One of the challenges presented by Candida infections is that many of the isolates encountered in the clinic produce biofilms, which can decrease these pathogens’ susceptibilities to standard-of-care antibiotic therapies. Inhibitors of fungal biofilm formation offer a potential solution to counteracting some of the problems associated with Candida infections. A screening campaign utilizing samples from our fungal extract library revealed that a Bionectria ochroleuca isolate cultured on Cheerios breakfast cereal produced metabolites that blocked the in vitro formation of Candida albicans biofilms. A scale-up culture of the fungus was undertaken using mycobags (also known as mushroom bags or spawn bags), which afforded four known [TMC-151s C–F (1–4)] and three new [bionectriols B–D (5–7)] polyketide glycosides. All seven metabolites exhibited potent biofilm inhibition against C. albicans SC5314, as well as exerted synergistic antifungal activities in combination with amphotericin B. In this report, we describe the structure determination of the new metabolites, as well as compare the secondary metabolome profiles of fungi grown in flasks and mycobags. These studies demonstrate that mycobags offer a useful alternative to flask-based cultures for the preparative production of fungal secondary metabolites. PMID:25302529

  4. Occurrence, isolation and differentiation of Candida spp. and prevalence of variables associated to chronic atrophic candidiasis.

    PubMed

    Lund, Rafael Guerra; da Silva Nascente, Patrícia; Etges, Adriana; Ribeiro, Gladis Aver; Rosalen, Pedro Luiz; Del Pino, Francisco Augusto Burkert

    2010-05-01

    The purpose of this study was to survey the frequency of Candida spp. in patients with chronic atrophic candidiasis (CAC), to differentiate Candida species and to assess the prevalence of certain infection-associated variables to this disease. Patients with CAC and wearing partial or complete dentures were recruited. Data were obtained by means of a questionnaire with details involving identification of the subject, demographic characteristics, behaviour and medical history, clinical and mycological evaluation and identification of yeast. The sample collection was carried out in the palate or palate and tongue of the subjects using sterilised swabs. Data were submitted to statistical analyses using Fischer's test. Forty-three (53%) cases of CAC showed the presence of Candida albicans. Females (75.2%) wearing complete dentures (60.1%) for more than 10 years (58%) were risk factors to CAC development. It could be concluded that: (a) the results did not confirm a significant difference among patients with CAC concerning the presence or absence of Candida spp.; (b) the occurrence of Candida was negatively related to important factors associated to this opportunistic infection; and (c) mycological findings did not indicate that the variables investigated have a significant effect on oral infections by C. albicans or other Candida species.

  5. Acid production by oral strains of Candida albicans and lactobacilli.

    PubMed

    Klinke, T; Kneist, S; de Soet, J J; Kuhlisch, E; Mauersberger, S; Forster, A; Klimm, W

    2009-01-01

    Both Candida albicans and lactobacilli are common colonizers of carious lesions in children and adolescents. The purpose of this study is to compare the velocity of acid production between C. albicans and several Lactobacillus species at different pH levels and concentrations of glucose. Washed, pure resting-cell suspensions were obtained by culturing a total of 28 oral isolates comprising the species C. albicans, Lactobacillus rhamnosus, Lactobacillus paracasei paracasei, Lactobacillus paracasei tolerans and Lactobacillus delbrueckii lactis. Acid production from glucose was determined at a constant pH of 7.0, 5.5, 5.0 and 4.0 by repeated titrations with NaOH in an automated pH-stat system. Acid formation rates of yeast and lactobacilli proved to be similar at both neutral and low pH, while in a moderately acidic environment C. albicans produced less acid than the lactobacilli. Ion chromatographic analysis of the cell-free medium after titration revealed pyruvate to be the predominant organic acid anion secreted by C. albicans. The proportion of organic acids to overall acid production by the yeast was below 10% at neutral conditions, in contrast to 42-66% at pH 4.0. Compared to lactobacilli, yeast required a concentration of glucose that was about 50 times higher to allow acid production at half the maximum speed. Considering the clinical data in the literature about the frequency and proportions of microorganisms present in early childhood caries lesions, the contribution of oral lactobacilli as well as C. albicans to overall microbial acid formation appears to be important. PMID:19246906

  6. Spaceflight Enhances Cell Aggregation and Random Budding in Candida albicans

    PubMed Central

    Woolley, Christine M.; Barrila, Jennifer; Buchanan, Kent; McCracken, James; Inglis, Diane O.; Searles, Stephen C.; Nelman-Gonzalez, Mayra A.; Ott, C. Mark; Wilson, James W.; Pierson, Duane L.; Stefanyshyn-Piper, Heidemarie M.; Hyman, Linda E.; Nickerson, Cheryl A.

    2013-01-01

    This study presents the first global transcriptional profiling and phenotypic characterization of the major human opportunistic fungal pathogen, Candida albicans, grown in spaceflight conditions. Microarray analysis revealed that C. albicans subjected to short-term spaceflight culture differentially regulated 452 genes compared to synchronous ground controls, which represented 8.3% of the analyzed ORFs. Spaceflight-cultured C. albicans–induced genes involved in cell aggregation (similar to flocculation), which was validated by microscopic and flow cytometry analysis. We also observed enhanced random budding of spaceflight-cultured cells as opposed to bipolar budding patterns for ground samples, in accordance with the gene expression data. Furthermore, genes involved in antifungal agent and stress resistance were differentially regulated in spaceflight, including induction of ABC transporters and members of the major facilitator family, downregulation of ergosterol-encoding genes, and upregulation of genes involved in oxidative stress resistance. Finally, downregulation of genes involved in actin cytoskeleton was observed. Interestingly, the transcriptional regulator Cap1 and over 30% of the Cap1 regulon was differentially expressed in spaceflight-cultured C. albicans. A potential role for Cap1 in the spaceflight response of C. albicans is suggested, as this regulator is involved in random budding, cell aggregation, and oxidative stress resistance; all related to observed spaceflight-associated changes of C. albicans. While culture of C. albicans in microgravity potentiates a global change in gene expression that could induce a virulence-related phenotype, no increased virulence in a murine intraperitoneal (i.p.) infection model was observed under the conditions of this study. Collectively, our data represent an important basis for the assessment of the risk that commensal flora could play during human spaceflight missions. Furthermore, since the low fluid

  7. Acid production by oral strains of Candida albicans and lactobacilli.

    PubMed

    Klinke, T; Kneist, S; de Soet, J J; Kuhlisch, E; Mauersberger, S; Forster, A; Klimm, W

    2009-01-01

    Both Candida albicans and lactobacilli are common colonizers of carious lesions in children and adolescents. The purpose of this study is to compare the velocity of acid production between C. albicans and several Lactobacillus species at different pH levels and concentrations of glucose. Washed, pure resting-cell suspensions were obtained by culturing a total of 28 oral isolates comprising the species C. albicans, Lactobacillus rhamnosus, Lactobacillus paracasei paracasei, Lactobacillus paracasei tolerans and Lactobacillus delbrueckii lactis. Acid production from glucose was determined at a constant pH of 7.0, 5.5, 5.0 and 4.0 by repeated titrations with NaOH in an automated pH-stat system. Acid formation rates of yeast and lactobacilli proved to be similar at both neutral and low pH, while in a moderately acidic environment C. albicans produced less acid than the lactobacilli. Ion chromatographic analysis of the cell-free medium after titration revealed pyruvate to be the predominant organic acid anion secreted by C. albicans. The proportion of organic acids to overall acid production by the yeast was below 10% at neutral conditions, in contrast to 42-66% at pH 4.0. Compared to lactobacilli, yeast required a concentration of glucose that was about 50 times higher to allow acid production at half the maximum speed. Considering the clinical data in the literature about the frequency and proportions of microorganisms present in early childhood caries lesions, the contribution of oral lactobacilli as well as C. albicans to overall microbial acid formation appears to be important.

  8. Factors supporting cysteine tolerance and sulfite production in Candida albicans.

    PubMed

    Hennicke, Florian; Grumbt, Maria; Lermann, Ulrich; Ueberschaar, Nico; Palige, Katja; Böttcher, Bettina; Jacobsen, Ilse D; Staib, Claudia; Morschhäuser, Joachim; Monod, Michel; Hube, Bernhard; Hertweck, Christian; Staib, Peter

    2013-04-01

    The amino acid cysteine has long been known to be toxic at elevated levels for bacteria, fungi, and humans. However, mechanisms of cysteine tolerance in microbes remain largely obscure. Here we show that the human pathogenic yeast Candida albicans excretes sulfite when confronted with increasing cysteine concentrations. Mutant construction and phenotypic analysis revealed that sulfite formation from cysteine in C. albicans relies on cysteine dioxygenase Cdg1, an enzyme with similar functions in humans. Environmental cysteine induced not only the expression of the CDG1 gene in C. albicans, but also the expression of SSU1, encoding a putative sulfite efflux pump. Accordingly, the deletion of SSU1 resulted in enhanced sensitivity of the fungal cells to both cysteine and sulfite. To study the regulation of sulfite/cysteine tolerance in more detail, we screened a C. albicans library of transcription factor mutants in the presence of sulfite. This approach and subsequent independent mutant analysis identified the zinc cluster transcription factor Zcf2 to govern sulfite/cysteine tolerance, as well as cysteine-inducible SSU1 and CDG1 gene expression. cdg1Δ and ssu1Δ mutants displayed reduced hypha formation in the presence of cysteine, indicating a possible role of the newly proposed mechanisms of cysteine tolerance and sulfite secretion in the pathogenicity of C. albicans. Moreover, cdg1Δ mutants induced delayed mortality in a mouse model of disseminated infection. Since sulfite is toxic and a potent reducing agent, its production by C. albicans suggests diverse roles during host adaptation and pathogenicity.

  9. Histone deacetylase-mediated morphological transition in Candida albicans.

    PubMed

    Kim, Jueun; Lee, Ji-Eun; Lee, Jung-Shin

    2015-12-01

    Candida albicans is the most common opportunistic fungal pathogen, which switches its morphology from single-cell yeast to filament through the various signaling pathways responding to diverse environmental cues. Various transcriptional factors such as Nrg1, Efg1, Brg1, Ssn6, and Tup1 are the key components of these signaling pathways. Since C. albicans can regulate its transcriptional gene expressions using common eukaryotic regulatory systems, its morphological transition by these signaling pathways could be linked to the epigenetic regulation by chromatin structure modifiers. Histone proteins, which are critical components of eukaryotic chromatin structure, can regulate the eukaryotic chromatin structure through their own modifications such as acetylation, methylation, phosphorylation and ubiquitylation. Recent studies revealed that various histone modifications, especially histone acetylation and deacetylation, participate in morphological transition of C. albicans collaborating with well-known transcription factors in the signaling pathways. Here, we review recent studies about chromatin-mediated morphological transition of C. albicans focusing on the interaction between transcription factors in the signaling pathways and histone deacetylases.

  10. Detection of Candida albicans by mass spectrometric fingerprinting.

    PubMed

    Zehm, Sarah; Schweinitz, Simone; Würzner, Reinhard; Colvin, Hans Peter; Rieder, Josef

    2012-03-01

    Candida albicans is one of the most frequent causes of fungal infections in humans. Significant correlation between candiduria and invasive candidiasis has previously been described. The existing diagnostic methods are often time-consuming, cost-intensive and lack in sensitivity and specificity. In this study, the profile of low-molecular weight volatile compounds in the headspace of C. albicans-urine suspensions of four different fungal cell concentrations compared to nutrient media and urine without C. albicans was determined using proton-transfer reaction mass spectrometry (PTR-MS). At fungal counts of ≥1.5 × 10(5) colony forming units (CFU)/ml signals at 45, 47 and 73 atomic mass units (amu) highly significantly increased. At fungal counts of <1.5 × 10(5) CFU/ml signals at 47 and 73 amu also increased, but only at 45 amu a statistically significant increase was seen. Time course alterations of signal intensities dependent on different cell concentrations and after addition of Sabouraud nutrient solution were analysed. Recommendations for measurement conditions are given. Our study is the first to describe headspace profiling of C. albicans-urine suspensions of different fungal cell concentrations. PTR-MS represents a promising approach to rapid, highly sensitive and non-invasive clinical diagnostics allowing qualitative and quantitative analysis.

  11. Hydrophobic polyoxins are resistant to intracellular degradation in Candida albicans.

    PubMed Central

    Smith, H A; Shenbagamurthi, P; Naider, F; Kundu, B; Becker, J M

    1986-01-01

    Two novel polyoxins, N-epsilon-(octanoyl)-lysyl-uracil polyoxin C (Oct-Lys-UPOC) and N-gamma-(octyl)-glutaminyluracil polyoxin C (Oct-Gln-UPOC), were synthesized by reacting uracil polyoxin C with the appropriate amino acid p-nitrophenyl ester. Oct-Lys-UPOC and Oct-Gln-UPOC were strong inhibitors (Kis = 1.7 X 10(-6)M) of chitin synthetase from Candida albicans membrane preparations. In a permeabilized-cell assay, Oct-Gln-UPOC had a 10-fold-lower inhibitory activity toward chitin synthetase than did the Oct-Lys-UPOC analog. Both compounds were resistant to hydrolysis by a cell extract of C. albicans H317; however, Oct-Gln-UPOC was hydrolyzed with a half-life of 23 min by a permeabilized-cell preparation. Oct-Lys-UPOC was resistant to hydrolysis by permeabilized cells. Oct-Gln-UPOC and Oct-Lys-UPOC did not compete with the transport of peptides or uridine into the cell. At concentrations up to 2 mM these two new polyoxins were ineffective in the inhibition of cell growth or reduction of cell viability, but they induced aberrant morphologies in C. albicans at a concentration of 0.25 mM. These data suggest that polyoxins containing hydrophobic amino acids retain strong chitin synthetase inhibitory activity and are resistant to cellular hydrolysis. They provide the first example of effective synthetic chitin synthetase inhibitors which are stable inside C. albicans. PMID:3524423

  12. Disruption of Sphingolipid Biosynthesis Blocks Phagocytosis of Candida albicans

    PubMed Central

    Schmidt, Florian I.; Freinkman, Elizaveta; Dougan, Stephanie; Dougan, Michael; Esteban, Alexandre; Maruyama, Takeshi; Strijbis, Karin; Ploegh, Hidde L.

    2015-01-01

    The ability of phagocytes to clear pathogens is an essential attribute of the innate immune response. The role of signaling lipid molecules such as phosphoinositides is well established, but the role of membrane sphingolipids in phagocytosis is largely unknown. Using a genetic approach and small molecule inhibitors, we show that phagocytosis of Candida albicans requires an intact sphingolipid biosynthetic pathway. Blockade of serine-palmitoyltransferase (SPT) and ceramide synthase-enzymes involved in sphingolipid biosynthesis- by myriocin and fumonisin B1, respectively, impaired phagocytosis by phagocytes. We used CRISPR/Cas9-mediated genome editing to generate Sptlc2-deficient DC2.4 dendritic cells, which lack serine palmitoyl transferase activity. Sptlc2-/- DC2.4 cells exhibited a stark defect in phagocytosis, were unable to bind fungal particles and failed to form a normal phagocytic cup to engulf C. albicans. Supplementing the growth media with GM1, the major ganglioside present at the cell surface, restored phagocytic activity of Sptlc2-/- DC2.4 cells. While overall membrane trafficking and endocytic pathways remained functional, Sptlc2-/- DC2.4 cells express reduced levels of the pattern recognition receptors Dectin-1 and TLR2 at the cell surface. Consistent with the in vitro data, compromised sphingolipid biosynthesis in mice sensitizes the animal to C. albicans infection. Sphingolipid biosynthesis is therefore critical for phagocytosis and in vivo clearance of C. albicans. PMID:26431038

  13. Disruption of Sphingolipid Biosynthesis Blocks Phagocytosis of Candida albicans.

    PubMed

    Tafesse, Fikadu G; Rashidfarrokhi, Ali; Schmidt, Florian I; Freinkman, Elizaveta; Dougan, Stephanie; Dougan, Michael; Esteban, Alexandre; Maruyama, Takeshi; Strijbis, Karin; Ploegh, Hidde L

    2015-10-01

    The ability of phagocytes to clear pathogens is an essential attribute of the innate immune response. The role of signaling lipid molecules such as phosphoinositides is well established, but the role of membrane sphingolipids in phagocytosis is largely unknown. Using a genetic approach and small molecule inhibitors, we show that phagocytosis of Candida albicans requires an intact sphingolipid biosynthetic pathway. Blockade of serine-palmitoyltransferase (SPT) and ceramide synthase-enzymes involved in sphingolipid biosynthesis- by myriocin and fumonisin B1, respectively, impaired phagocytosis by phagocytes. We used CRISPR/Cas9-mediated genome editing to generate Sptlc2-deficient DC2.4 dendritic cells, which lack serine palmitoyl transferase activity. Sptlc2-/- DC2.4 cells exhibited a stark defect in phagocytosis, were unable to bind fungal particles and failed to form a normal phagocytic cup to engulf C. albicans. Supplementing the growth media with GM1, the major ganglioside present at the cell surface, restored phagocytic activity of Sptlc2-/- DC2.4 cells. While overall membrane trafficking and endocytic pathways remained functional, Sptlc2-/- DC2.4 cells express reduced levels of the pattern recognition receptors Dectin-1 and TLR2 at the cell surface. Consistent with the in vitro data, compromised sphingolipid biosynthesis in mice sensitizes the animal to C. albicans infection. Sphingolipid biosynthesis is therefore critical for phagocytosis and in vivo clearance of C. albicans.

  14. Effects of ambroxol on Candida albicans growth and biofilm formation.

    PubMed

    Rene, Hernandez-Delgadillo; José, Martínez-Sanmiguel Juan; Isela, Sánchez-Nájera Rosa; Claudio, Cabral-Romero

    2014-04-01

    Typically, the onset of candidiasis is characterised by the appearance of a biofilm of Candida albicans, which is associated with several diseases including oral candidiasis in young and elderly people. The objective of this work was to investigate the in vitro fungicidal activity as well as the antibiofilm activity of ambroxol (AMB) against C. albicans growth. In the present investigation, the fungicidal activity of AMB was established using the cell viability 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Also the minimum inhibitory concentration (MIC) of AMB required to inhibit the fungal growth was determined. Simultaneously, the antibiofilm activity of AMB was evaluated using fluorescence microscopy. The study revealed that 2 mg ml(-1) of AMB exhibited higher fungicidal activity than 3.3 mg ml(-1) of terbinafine, one of most common commercial antifungals. A MIC of 1 mg ml(-1) was determined for AMB to interfere with C. albicans growth. Furthermore, AMB was found to be effective in inhibiting the biofilm formation of C. albicans and exerted its fungicidal activity against the fungal cells interspersed in the preformed biofilm. The study suggests a potential role of the mucolytic agent, AMB, as an interesting therapeutic alternative in the treatment of oral candidiasis.

  15. Effects of ambroxol on Candida albicans growth and biofilm formation.

    PubMed

    Rene, Hernandez-Delgadillo; José, Martínez-Sanmiguel Juan; Isela, Sánchez-Nájera Rosa; Claudio, Cabral-Romero

    2014-04-01

    Typically, the onset of candidiasis is characterised by the appearance of a biofilm of Candida albicans, which is associated with several diseases including oral candidiasis in young and elderly people. The objective of this work was to investigate the in vitro fungicidal activity as well as the antibiofilm activity of ambroxol (AMB) against C. albicans growth. In the present investigation, the fungicidal activity of AMB was established using the cell viability 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Also the minimum inhibitory concentration (MIC) of AMB required to inhibit the fungal growth was determined. Simultaneously, the antibiofilm activity of AMB was evaluated using fluorescence microscopy. The study revealed that 2 mg ml(-1) of AMB exhibited higher fungicidal activity than 3.3 mg ml(-1) of terbinafine, one of most common commercial antifungals. A MIC of 1 mg ml(-1) was determined for AMB to interfere with C. albicans growth. Furthermore, AMB was found to be effective in inhibiting the biofilm formation of C. albicans and exerted its fungicidal activity against the fungal cells interspersed in the preformed biofilm. The study suggests a potential role of the mucolytic agent, AMB, as an interesting therapeutic alternative in the treatment of oral candidiasis. PMID:24224742

  16. Low virulent oral Candida albicans strains isolated from smokers.

    PubMed

    de Azevedo Izidoro, Ana Claudia Santos; Semprebom, Andressa Marafon; Baboni, Fernanda Brasil; Rosa, Rosimeire Takaki; Machado, Maria Angela Naval; Samaranayake, Lakshman Perera; Rosa, Edvaldo Antonio Ribeiro

    2012-02-01

    It is widely accepted that tabagism is a predisposing factor to oral candidosis and cumulate data suggest that cigarette compounds may increase candidal virulence. To verify if enhanced virulence occurs in Candida albicans from chronic smokers, a cohort of 42 non-smokers and other of 58 smokers (all with excellent oral conditions and without signs of candidosis) were swabbed on tong dorsum and jugal mucosa. Results showed that oral candidal loads do not differ between smoker and non-smokers. Activities of secreted aspartyl-protease (Sap), phospholipase, chondroitinase, esterase-lipase, and haemolysin secretions were screened for thirty-two C. albicans isolates. There were detected significant increments in phospholipasic and chondroitinasic activities in isolates from non-smokers. For other virulence factors, no differences between both cohorts were achieved. PMID:21924704

  17. Molecular cloning and characterization of chitinase genes from Candida albicans.

    PubMed Central

    McCreath, K J; Specht, C A; Robbins, P W

    1995-01-01

    Chitinase (EC 3.2.1.14) is an important enzyme for the remodeling of chitin in the cell wall of fungi. We have cloned three chitinase genes (CHT1, CHT2, and CHT3) from the dimorphic human pathogen Candida albicans. CHT2 and CHT3 have been sequenced in full and their primary structures have been analyzed: CHT2 encodes a protein of 583 aa with a predicted size of 60.8 kDa; CHT3 encodes a protein of 567 aa with a predicted size of 60 kDa. All three genes show striking similarity to other chitinase genes in the literature, especially in the proposed catalytic domain. Transcription of CHT2 and CHT3 was greater when C. albicans was grown in a yeast phase as compared to a mycelial phase. A transcript of CHT1 could not be detected in either growth condition. Images Fig. 2 Fig. 5 PMID:7708682

  18. Adaptation of Candida albicans to commensalism in the gut.

    PubMed

    Prieto, Daniel; Correia, Inês; Pla, Jesús; Román, Elvira

    2016-01-01

    Candida albicans is a common resident of the oral cavity, GI tract and vagina in healthy humans where it establishes a commensal relationship with the host. Colonization of the gut, which is an important niche for the microbe, may lead to systemic dissemination and disease upon alteration of host defences. Understanding the mechanisms responsible for the adaptation of C. albicans to the gut is therefore important for the design of new ways of combating fungal diseases. In this review we discuss the available models to study commensalism of this yeast, the main mechanisms controlling the establishment of the fungus, such as microbiota, mucus layer and antimicrobial peptides, and the gene regulatory circuits that ensure its survival in this niche.

  19. Lemongrass-Incorporated Tissue Conditioner Against Candida albicans Culture

    PubMed Central

    Amornvit, Pokpong; Srithavaj, Theerathavaj

    2014-01-01

    Background: Tissue conditioner is applied popularly with dental prosthesis during wound healing process but it becomes a reservoir of oral microbiota, especially Candida species after long-term usage. Several antifungal drugs have been mixed with this material to control fungal level. In this study, lemongrass essential oil was added into COE-COMFORT tissue conditioner before being determined for anti-Candida efficacy. Materials and Methods: Lemongrass (Cymbopogon citratus) essential oil was primarily determined for antifungal activity against C. albicans American type culture collection (ATCC) 10231 and MIC (minimum inhibitory concentration) value by agar disk diffusion and broth microdilution methods, respectively. COE-COMFORT tissue conditioner was prepared as recommended by the manufacturer after a fixed volume of the oil at its MIC or higher concentrations were mixed thoroughly in its liquid part. Antifungal efficacy of the tissue conditioner with/without herb was finally analyzed. Results: Lemongrass essential oil displayed potent antifungal activity against C. albicans ATCC 10231and its MIC value was 0.06% (v/v). Dissimilarly, the tissue conditioner containing the oil at MIC level did not cease the growth of the tested fungus. Both reference and clinical isolates of C. albicans were completely inhibited after exposed to the tissue conditioner containing at least 0.25% (v/v) of the oil (approximately 4-time MIC). The tissue conditioner without herb or with nystatin was employed as negative or positive control, respectively. Conclusion: COE-COMFORT tissue conditioner supplemented with lemongrass essential oil obviously demonstrated another desirable property as in vitro anti-Candida efficacy to minimize the risk of getting Candidal infection. PMID:25177638

  20. Medical treatment of a pacemaker endocarditis due to Candida albicans and to Candida glabrata.

    PubMed

    Roger, P M; Boissy, C; Gari-Toussaint, M; Foucher, R; Mondain, V; Vandenbos, F; le Fichoux, Y; Michiels, J F; Dellamonica, P

    2000-09-01

    We describe a case of pacemaker infection due to two fungal species: Candida albicans and C. glabrata. Transthoracic echocardiography showed a large vegetation on the intraventricular wires. Because of severe underlying diseases, surgery was believed to be contraindicated. The patient was treated using high dose of fluconazole, resulting in clinical improvement and negative blood cultures. However, 2 months later, the patient underwent a fatal stroke. At autopsy, a large vegetation was found only all along the wires. Postmortem culture of the infected material was positive for both C. albicans and C. glabrata. PMID:11023765

  1. Variation of electrophoretic karyotypes among clinical isolates of Candida albicans.

    PubMed Central

    Merz, W G; Connelly, C; Hieter, P

    1988-01-01

    Orthogonal-field-alternation gel electrophoresis was used to compare clinical isolates of Candida albicans by resolving chromosome-sized DNA molecules into an electrophoretic karyotype. Seven to nine bands were observed among isolates recovered from 17 patients. In addition, 14 distinct electrophoretic patterns were noted among the isolates from these patients. In a given individual, isolates were likely to have identical electrophoretic patterns. Therefore, the electrophoretic karyotype patterns demonstrated by orthogonal-field-alternation gel electrophoresis can be used to designate a strain for epidemiologic studies. Images PMID:3290238

  2. Interactions between amphotericin B and nitroimidazoles against Candida albicans.

    PubMed

    Cury, A E; Hirschfeld, M P

    1997-10-01

    This work proved that nitroimidazole antiprotozoal agents, such as metronidazole, ornidazole, secnidazole and tinidazole, in concentrations of up to 64 micrograms ml-1 did not present any antifungal activity against 17 strains of Candida albicans. The combination of each drug with amphotericin B showed the occurrence of variable interactions according to the studied strain. Promising results were observed based on synergistic and additive interactions of the polyene with the metronidazole; the inhibitory and lethal activities of the drugs were potentiated against all strains in concentrations reachable in vivo. PMID:9476486

  3. Protective and pathologic immune responses against Candida albicans infection.

    PubMed

    Ashman, Robert B

    2008-05-01

    Candida albicans is an important opportunistic fungal pathogen. Clinical observations have indicated that both innate and adaptive immune responses are involved in recovery from initial infection, but analysis in murine models has shown that the contribution of the two arms of the cellular immune response differ in oral, vaginal, and systemic infections. The relative contributions of T cells and phagocytic cells, and the cytokines that mediate their interactions are discussed for each of the different manifestations of the disease, and the consequences of infection, in terms of protection and pathology, are evaluated.

  4. In vitro interactions between anidulafungin and nonsteroidal anti-inflammatory drugs on biofilms of Candida spp.

    PubMed

    Rosato, Antonio; Catalano, Alessia; Carocci, Alessia; Carrieri, Antonio; Carone, Addolorata; Caggiano, Giuseppina; Franchini, Carlo; Corbo, Filomena; Montagna, Maria Teresa

    2016-03-01

    Candida spp. are responsible for many biomaterial-related infections; they give rise to infective pathologies typically associated with biofilm formation. We recently reported that the echinocandin anidulafungin (ANF) showed a strong in vitro activity against both planktonic and biofilms cells. Herein, we report the antifungal activities of ANF alone and in association with some non-steroidal anti-inflammatory drugs (NSAIDs) against nine Candida strain biofilms: four Candida albicans, two Candida glabrata and three Candida guilliermondii. The activity of ANF was assessed using an in vitro microbiological model relevant for clinical practice. ANF proved oneself to be active against biofilms cells, and a clear-cut synergism was found against Candida species biofilms when ANF was used in combination with three NSAIDs: aspirin, diclofenac, ibuprofen. The positive synergism against Candida spp. of ANF in association with aspirin or the other NSAIDs proved to be a very effective antifungal treatment (FICI<0.5). These results may provide the starting point for new combination therapies of ANF with NSAIDs against Candida biofilm pathologies.

  5. Antifungal activities of origanum oil against Candida albicans.

    PubMed

    Manohar, V; Ingram, C; Gray, J; Talpur, N A; Echard, B W; Bagchi, D; Preuss, H G

    2001-12-01

    The antimicrobial properties of volatile aromatic oils from medicinal as well as other edible plants has been recognized since antiquity. Origanum oil, which is used as a food flavoring agent, possesses a broad spectrum of in vitro antimicrobial activities attributed to the high content of phenolic derivatives such as carvacrol and thymol. In the present study, antifungal properties of origanum oil were examined both in vitro and in vivo. Using Candida albicans in broth cultures and a micro dilution method, comparative efficacy of origanum oil, carvacrol, nystatin and amphotericin B were examined in vitro. Origanum oil at 0.25 mg/ml was found to completely inhibit the growth of C. albicans in culture. Growth inhibitions of 75% and >50% were observed at 0.125 mg/ml and 0.0625 mg/ml level, respectively. In addition, both the germination and the mycelial growth of C. albicans were found to be inhibited by origanum oil and carvacrol in a dose-dependent manner. Furthermore, the therapeutic efficacy of origanum oil was examined in an experimental murine systemic candidiasis model. Groups of mice (n = 6) infected with C. albicans (5 x LD50) were fed varying amounts of origanum oil in a final vol. of 0.1 ml of olive oil (vehicle). The daily administration of 8.6 mg of origanum oil in 100 microl of olive oil/kg body weight for 30 days resulted in 80% survivability, with no renal burden of C. albicans as opposed to the group of mice fed olive oil alone, who died within 10 days. Similar results were obtained with carvacrol. However, mice fed origanum oil exhibited cosmetically better clinical appearance compared to those cured with carvacrol. The results from our study encourage examination of the efficacy of origanum oil in other forms of systemic and superficial fungal infections and exploration of its broad spectrum effect against other pathogenic manifestations including malignancy. PMID:11855736

  6. Ultrastructural Analysis of Candida albicans When Exposed to Silver Nanoparticles

    PubMed Central

    Vazquez-Muñoz, Roberto; Avalos-Borja, Miguel; Castro-Longoria, Ernestina

    2014-01-01

    Candida albicans is the most common fungal pathogen in humans, and recently some studies have reported the antifungal activity of silver nanoparticles (AgNPs) against some Candida species. However, ultrastructural analyses on the interaction of AgNPs with these microorganisms have not been reported. In this work we evaluated the effect of AgNPs on C. albicans, and the minimum inhibitory concentration (MIC) was found to have a fungicidal effect. The IC50 was also determined, and the use of AgNPs with fluconazole (FLC), a fungistatic drug, reduced cell proliferation. In order to understand how AgNPs interact with living cells, the ultrastructural distribution of AgNPs in this fungus was determined. Transmission electron microscopy (TEM) analysis revealed a high accumulation of AgNPs outside the cells but also smaller nanoparticles (NPs) localized throughout the cytoplasm. Energy dispersive spectroscopy (EDS) analysis confirmed the presence of intracellular silver. From our results it is assumed that AgNPs used in this study do not penetrate the cell, but instead release silver ions that infiltrate into the cell leading to the formation of NPs through reduction by organic compounds present in the cell wall and cytoplasm. PMID:25290909

  7. Systemic Candida albicans infection in two alpacas (Lama pacos).

    PubMed

    Kramer, K; Haist, V; Roth, C; Schröder, C; Siesenhop, U; Baumgärtner, W; Wohlsein, P

    2008-01-01

    Systemic Candida albicans infection was diagnosed in two adult alpaca stallions originating from different herds. Case 1 had a history of chronic dermatitis with unknown aetiology that had been treated long-term with glucocorticoids. Case 2 had suffered from transient facial paralysis and psoroptic mange of the external ear. Both animals died suddenly after recovering from their initial disorders. Necropsy examination of case 1 revealed multifocal erosive dermatitis, thoracic and abdominal serofibrinous effusions, and multiple suppurative foci in lung, myocardium, kidney, pancreas and brain. Case 2 had multiple ulcers of the third gastric compartment and focal suppurative nephritis. Additionally, moderate depletion of lymphoid organs was observed in both animals. Histologically, suppurative to necrotizing inflammation with necrotizing vasculitis was present in the grossly affected organs of both animals. Yeast, pseudohyphae and branching hyphae were present within these lesions and C. albicans was isolated from lesional tissue of both animals. The primary site of Candida invasion was not determined in case 1, but the most likely portal of entry in case 2 was the gastric ulcers. Depletion of lymphoid tissue suggested a possible underlying immune suppression in both animals.

  8. Chloroquine sensitizes biofilms of Candida albicans to antifungal azoles.

    PubMed

    Shinde, Ravikumar Bapurao; Raut, Jayant Shankar; Chauhan, Nitin Mahendra; Karuppayil, Sankunny Mohan

    2013-01-01

    Biofilms formed by Candida albicans, a human pathogen, are known to be resistant to different antifungal agents. Novel strategies to combat the biofilm associated Candida infections like multiple drug therapy are being explored. In this study, potential of chloroquine to be a partner drug in combination with four antifungal agents, namely fluconazole, voriconazole, amphotericin B, and caspofungin, was explored against biofilms of C. albicans. Activity of various concentrations of chloroquine in combination with a particular antifungal drug was analyzed in a checkerboard format. Growth of biofilm in presence of drugs was analyzed by XTT-assay, in terms of relative metabolic activity compared to that of drug free control. Results obtained by XTT-metabolic assay were confirmed by scanning electron microscopy. The interactions between chloroquine and four antifungal drugs were determined by calculating fractional inhibitory concentration indices. Azole resistance in biofilms was reverted significantly (p<0.05) in presence of 250μg/mL of chloroquine, which resulted in inhibition of biofilms at very low concentrations of antifungal drugs. No significant alteration in the sensitivity of biofilms to caspofungin and amphotericin B was evident in combination with chloroquine. This study for the first time indicates that chloroquine potentiates anti-biofilm activity of fluconazole and voriconazole. PMID:23602464

  9. The ABCs of Candida albicans Multidrug Transporter Cdr1

    PubMed Central

    Banerjee, Atanu; Khandelwal, Nitesh Kumar; Dhamgaye, Sanjiveeni

    2015-01-01

    In the light of multidrug resistance (MDR) among pathogenic microbes and cancer cells, membrane transporters have gained profound clinical significance. Chemotherapeutic failure, by far, has been attributed mainly to the robust and diverse array of these proteins, which are omnipresent in every stratum of the living world. Candida albicans, one of the major fungal pathogens affecting immunocompromised patients, also develops MDR during the course of chemotherapy. The pivotal membrane transporters that C. albicans has exploited as one of the strategies to develop MDR belongs to either the ATP binding cassette (ABC) or the major facilitator superfamily (MFS) class of proteins. The ABC transporter Candida drug resistance 1 protein (Cdr1p) is a major player among these transporters that enables the pathogen to outplay the battery of antifungals encountered by it. The promiscuous Cdr1 protein fulfills the quintessential need of a model to study molecular mechanisms of multidrug transporter regulation and structure-function analyses of asymmetric ABC transporters. In this review, we cover the highlights of two decades of research on Cdr1p that has provided a platform to study its structure-function relationships and regulatory circuitry for a better understanding of MDR not only in yeast but also in other organisms. PMID:26407965

  10. SOME CYTOLOGICAL AND PATHOGENIC PROPERTIES OF SPHEROPLASTS OF CANDIDA ALBICANS

    PubMed Central

    Kobayashi, George S.; Friedman, Lorraine; Kofroth, Judith F.

    1964-01-01

    Kobayashi, George S. (Tulane University, New Orleans, La.), Lorraine Friedman, and Judith F. Kofroth. Some cytological and pathogenic properties of spheroplasts of Candida albicans. J. Bacteriol. 88:795–801. 1964.—Spheroplasts of Candida albicans were prepared by use of an enzymatic mixture from the digestive tract of the snail Helix pomatia. Untreated cells exhibited well-defined cell walls, whereas such structures were absent from spheroplasts. The intravenous inoculation of either spheroplasts or intact cells into rabbits produced a fever which was apparent within 30 min, the “immediate” fever response characteristic of microbial endotoxin. Cell-wall fragments of enzyme-treated cells did not induce a convincing pyrogenic response. When the inoculum was viable, body temperatures did not return to normal but remained elevated until death of the animal 1 or more days later, exhibiting the “delayed” fever of infection. The gross pathological picture in animals succumbing to infection by viable spheroplasts was similar to that obtained with untreated yeast cells. Images PMID:14208520

  11. Differentiation of Candida dubliniensis from Candida albicans on rosemary extract agar and oregano extract agar.

    PubMed

    de Loreto, Erico Silva; Pozzatti, Patrícia; Alves Scheid, Liliane; Santurio, Deise; Morais Santurio, Janio; Alves, Sydney Hartz

    2008-01-01

    Candida dubliniensis is a recently described pathogenic species which shares many phenotypic features with Candida albicans and therefore, may be misidentified in microbiological laboratories. Because molecular methods can be onerous and unfeasible in routine mycological laboratories with restricted budgets such as those in developing countries, phenotypic techniques have been encouraged in the development of differential media for the presumptive identification of these species. We examined the colony morphology and chlamydospore production of 30 C. dubliniensis isolates and 100 C. albicans isolates on two new proposed media: rosemary (Rosmarinus officinalis) extract agar (REA) and oregano (Origanum vulgare) extract agar (OEA). These substrates are traditionally used as spices and medicinal herbs. In both of these media, all C. dubliniensis isolates (100%) showed rough colonies with peripheral hyphal fringes and abundant chlamydospores after 24 to 48 hr of incubation at 25 degrees C. In contrast, under the same conditions, all isolates of C. albicans (100%) showed smooth colonies without hyphal fringes or chlamydospores. In conclusion, REA and OEA offer a simple, rapid, and inexpensive screening media for the differentiation of C. albicans and C. dubliniensis.

  12. Chromogenic medium for direct susceptibility testing of Candida spp. isolated from urine.

    PubMed

    de Vasconcelos, Antônio Alexandre; Menezes, Everardo Albuquerque; Cunha, Francisco Afrânio

    2011-08-01

    Currently, there has been an increased frequency of fungal infections. Candida albicans and other Candida spp. have been proven to be major causes for urinary tract infection. Increased resistance to antifungals indicates the need to develop strategies in order to prevent the spread of resistance. Chromogenic medium have been proven to be useful in the detection of yeasts in clinical specimens containing mixed cultures of Candida. The aim of this study was to compare the results of antifungal susceptibility testing with fluconazole and amphotericin B on strains of Candida spp. isolated from urine, conducted on a Mueller-Hinton Agar with Glucose and Methylene Blue (MHAGMB) medium and on a Hicrome Candida® Agar with 2% Glucose (HCAG) medium. We used 40 samples of Candida spp. isolated from urine samples from inpatients and outpatients. The results showed that both media presented high rates of agreement, above 94%. The use of the HCAG medium decreases the release time of the results by 24-48 h, which may be decisive for initiating the correct drug treatment.

  13. Distribution of Candida albicans genotypes among family members

    NASA Technical Reports Server (NTRS)

    Mehta, S. K.; Stevens, D. A.; Mishra, S. K.; Feroze, F.; Pierson, D. L.

    1999-01-01

    Thirty-three families (71 subjects) were screened for the presence of Candida albicans in mouthwash or stool specimens; 12 families (28 subjects) were culture-positive for this yeast. An enrichment procedure provided a twofold increase in the recovery of C. albicans from mouthwash specimens. Nine of the twelve culture-positive families had two positive members each, two families had three positive members each, and one family had four positive members. Genetic profiles were obtained by three methods: pulsed-field gel electrophoresis; restriction endonuclease analysis, and random amplification of polymorphic DNA analysis. DNA fingerprinting of C. albicans isolated from one body site three consecutive times revealed that each of the 12 families carried a distinct genotype. No two families shared the same strain, and two or more members of a family commonly shared the same strain. Intrafamily genotypic identity (i.e., each member within the family harbored the same strain) was demonstrated in six families. Genotypes of isolates from husband and wife differed from one another in five families. All three methods were satisfactory in determining genotypes; however, we concluded that restriction endonuclease analysis provided adequate resolving power.

  14. Potent Synergy between Spirocyclic Pyrrolidinoindolinones and Fluconazole against Candida albicans.

    PubMed

    Premachandra, Ilandari Dewage Udara Anulal; Scott, Kevin A; Shen, Chengtian; Wang, Fuqiang; Lane, Shelley; Liu, Haoping; Van Vranken, David L

    2015-10-01

    A spiroindolinone, (1S,3R,3aR,6aS)-1-benzyl-6'-chloro-5-(4-fluorophenyl)-7'-methylspiro[1,2,3a,6a-tetrahydropyrrolo[3,4-c]pyrrole-3,3'-1H-indole]-2',4,6-trione, was previously reported to enhance the antifungal effect of fluconazole against Candida albicans. A diastereomer of this compound was synthesized, along with various analogues. Many of the compounds were shown to enhance the antifungal effect of fluconazole against C. albicans, some with exquisite potency. One spirocyclic piperazine derivative, which we have named synazo-1, was found to enhance the effect of fluconazole with an EC50 value of 300 pM against a susceptible strain of C. albicans and going as low as 2 nM against some resistant strains. Synazo-1 exhibits true synergy with fluconazole, with an FIC index below 0.5 in the strains tested. Synazo-1 exhibited low toxicity in mammalian cells relative to the concentrations required for antifungal synergy.

  15. Superantigen-Like Effects of a Candida albicans Polypeptide

    PubMed Central

    Devore-Carter, Denise; Kar, Sujata; Vellucci, Vincent; Bhattacherjee, Vasker; Domanski, Paul; Hostetter, Margaret K.

    2008-01-01

    The amino terminal sequence of the Candida albicans cell wall protein Int1 exhibited partial identity with the major histocompatibility complex (MHC) class II binding site of the Mycoplasma arthritidis superantigen MAM. Int1-positive C. albicans blastospores activated human T lymphocytes and expanded Vβ subsets 2, 3, and/or 14; Int1-negative strains were inactive. Release of interferon-γ (IFN-γ) but not of tumor necrosis factor–α or interleukin-6 was Int1 dependent; interleukin-4 and interleukin-10 were not detected. T lymphocyte activation, Vβ expansion, and IFN-γ release were associated with a soluble polypeptide that encompassed the first 263 amino acids of Int1 (Pep263). Monoclonal antibody 163.5, which recognizes an Int1 epitope that overlaps the region of identity with MAM, significantly inhibited these activities when triggered by Int1-positive blastospores or Pep263 but not by staphylococcal enterotoxin B. Histidine263 was required. Pep263 bound to T lymphocytes and MHC class II and was detected in the urine of a patient with C. albicans fungemia. These studies identify a candidal protein that displays superantigen-like activities. PMID:18419534

  16. Gastrointestinal Colonization by Candida albicans Mutant Strains in Antibiotic-Treated Mice

    PubMed Central

    Wiesner, Stephen M.; Jechorek, Robert P.; Garni, Robb M.; Bendel, Catherine M.; Wells, Carol L.

    2001-01-01

    Antibiotic-treated mice orally inoculated with one of three Candida albicans strains (including two mutant strains) or indigenous Candida pelliculosa showed levels of candidal gastrointestinal colonization that were strain specific. However, regardless of strain, the numbers of viable candida were intermediate to high in the stomach, were consistently lowest in the upper small intestine, and increased progressively down the intestinal tract. PMID:11139219

  17. Vaginal epithelial cell anti-Candida albicans activity is associated with protection against symptomatic vaginal candidiasis.

    PubMed

    Barousse, Melissa M; Espinosa, Terri; Dunlap, Kathleen; Fidel, Paul L

    2005-11-01

    Vaginal epithelial cell (VEC) anti-Candida albicans activity, despite being measured in vitro, is considered an innate host defense mechanism. This was supported further by the fact that women protected from symptomatic infection following a live intravaginal Candida challenge had increased VEC anti-Candida activity compared to those who acquired a symptomatic infection.

  18. Binding of the extracellular matrix component entactin to Candida albicans.

    PubMed Central

    López-Ribot, J L; Chaffin, W L

    1994-01-01

    We have investigated the interaction between Candida albicans and entactin, a recently characterized glycoprotein present in the extracellular matrix, especially in the basement membrane. Organisms of both the yeast and the hyphal morphologies of the fungus had the ability to bind recombinant entactin, as detected by an indirect immunofluorescence assay. Material present in the 2-mercaptoethanol cell wall extracts from both C. albicans growth forms was capable of binding to immobilized recombinant entactin in a dose-dependent manner. Binding to entactin was approximately twice that observed for laminin. Binding of an extract component(s) to entactin was partially inhibited by an Arg-Gly-Asp-Ser peptide. A polyclonal antientactin antiserum, as well as a pooled antiserum preparation raised against components present in different C. albicans cell wall extracts, completely or almost completely abolished binding. The existence of morphology-specific receptor-like molecules which bind to different domains of the entactin molecule was ruled out in a competition binding assay. The entactin-binding material(s) in the cell wall also displayed some ability to bind laminin and fibronectin, since preadsorption in the presence of these extracellular matrix components resulted in reduction of binding to entactin. Moieties with a molecular mass of approximately 25, 44, and 65 kDa present in the 2-mercaptoethanol cell wall extracts from both blastoconidia and germ tubes were detected in a ligand affinity blotting experiment as having the ability to bind entactin. Interactions between C. albicans and entactin could be important in mediating adhesion of the fungus to the host tissues and may play a role in the establishment of the disseminated form of the disease. Images PMID:7927722

  19. Utilising polyphenols for the clinical management of Candida albicans biofilms.

    PubMed

    Shahzad, Muhammad; Sherry, Leighann; Rajendran, Ranjith; Edwards, Christine A; Combet, Emilie; Ramage, Gordon

    2014-09-01

    Polyphenols (PPs) are secondary metabolites abundant in plant-derived foods. They are reported to exhibit antimicrobial activity that may offer an alternative to existing antimicrobials. The aim of this study was to evaluate the antifungal potential of PPs against Candida albicans biofilms that are commonly recalcitrant to antifungal therapy. The antifungal activity of 14 PPs was assessed in terms of planktonic and sessile minimum inhibitory concentrations (PMICs and SMICs, respectively) against various C. albicans clinical isolates. The most active PPs were further tested for their effect on C. albicans adhesion and biofilm growth using standard biomass assays, microscopy and quantitative gene expression. Of the 14 PPs tested, 7 were effective inhibitors of planktonic growth, of which pyrogallol (PYG) was the most effective (PMIC₅₀=78 μg/mL), followed by curcumin (CUR) (PMIC₅₀=100 μg/mL) and pyrocatechol (PMIC₅₀=625 μg/mL). Both PYG and CUR displayed activity against C. albicans biofilms (SMIC₅₀=40 μg/mL and 50 μg/mL, respectively), although they did not disrupt the biofilm or directly affect the cellular structure. Overall, CUR displayed superior biofilm activity, significantly inhibiting initial cell adhesion following pre-coating (P<0.01), biofilm growth (P<0.05) and gene expression (P<0.05). This inhibitory effect diminished with prolonged CUR exposure, although it still inhibited by 50% after 4h adhesion. Overall, CUR exhibited positive antibiofilm properties that could be used at the basis for development of similar molecules, although further cellular and in vivo studies are required to explore its precise mechanism of action. PMID:25104135

  20. Antifungal effect of lavender honey against Candida albicans , Candida krusei and Cryptococcus neoformans.

    PubMed

    Estevinho, Maria Leticia; Afonso, Sílvia Esteves; Feás, Xesús

    2011-10-01

    Monofloral lavender honey samples (n = 30), were analyzed to test antifungal effect against Candida albicans, Candida krusei, and Cryptococcus neoformans. The specific growth rates (μ) showed that all the yeast growths were reduced in the presence of honey. The honey concentration (% w/v) that inhibited 10% of the yeasts growth (X min) ranged from 31.0% (C. albicans), 16.8% (C. krusei) and 23.0% (C. neoformans). A synthetic honey solution was also tested to determine antifungal activity attributable to sugars. The presence of synthetic honey in the C. krusei culture medium at concentrations above 58.0% (w/v) was established as X min, while C. albicans and C. neoformans were more resistant, since X min values were not reached over the ranged tested (10-60%, w/v). What the data suggests is that the component in the lavender honey responsible for the observed antifungal in vitro properties is not sugar based. Honey might be tapped as a natural resource to look for new medicines for the treatment of mycotic infections. This could be very useful, onsidering the increasing resistance of antifungals. It should be noticed that this is the first study concerning the effect of lavender honey on the growth of pathogenic yeasts.

  1. Experimental hematogenous candidiasis caused by Candida krusei and Candida albicans: species differences in pathogenicity.

    PubMed Central

    Anaissie, E; Hachem, R; K-Tin-U, C; Stephens, L C; Bodey, G P

    1993-01-01

    Hematogenous infections caused by Candida krusei have been noted with increasing frequency, particularly in cancer patients receiving prophylaxis with antifungal triazoles. Progress in understanding the pathogenesis of this emerging infection has been limited by the lack of an animal model. We developed a CF1 mouse intravenous inoculation model of candidiasis to evaluate the pathogenicity of C. krusei in normal and immunosuppressed mice and to compare it with that of Candida albicans. Several inocula (10(6) to 10(8) CFU per animal) of two clinical strains of C. krusei and three American Type Culture Collection strains of C. albicans were tested. Groups of 20 mice each were injected with a single intravenous dose of one inoculum. Animals randomized to receive C. krusei were immunosuppressed by intraperitoneal injection of cyclophosphamide or the combination of cyclophosphamide plus cortisone acetate or they did not receive immunosuppressive agents (normal mice). One hundred percent mortality was observed in normal mice injected with 10(6) CFU of C. albicans per mouse compared with no mortality in normal mice that received 10(8) CFU of C. krusei per mouse (P < 0.01). Resistance to C. krusei infection was markedly lowered by immunosuppression, particularly by the combination of cyclophosphamide plus cortisone acetate, with a significantly shorter survival and a higher organ fungal burden in immunosuppressed than in normal animals (P < 0.01). Tissue infection was documented by culture and histopathologic findings in all examined organs. Images PMID:8454330

  2. Effect of tyrosol on adhesion of Candida albicans and Candida glabrata to acrylic surfaces.

    PubMed

    Monteiro, Douglas Roberto; Feresin, Leonardo Perina; Arias, Laís Salomão; Barão, Valentim Adelino Ricardo; Barbosa, Debora Barros; Delbem, Alberto Carlos Botazzo

    2015-09-01

    The prevention of adhesion of Candida cells to acrylic surfaces can be regarded as an alternative to prevent denture stomatitis. The use of quorum sensing molecules, such as tyrosol, could potentially interfere with the adhesion process. Therefore, the aim of this study was to assess the effect of tyrosol on adhesion of single and mixed cultures of Candida albicans and Candida glabrata to acrylic resin surfaces. Tyrosol was diluted in each yeast inoculum (10(7) cells/ml in artificial saliva) at 25, 50, 100, and 200 mM. Then, each dilution was added to wells of 24-well plates containing the acrylic specimens, and the plates were incubated at 37°C for 2 h. After, the effect of tyrosol was determined by total biomass quantification, metabolic activity of the cells and colony-forming unit counting. Chlorhexidine gluconate (CHG) was used as a positive control. Data were analyzed using analysis of variance (ANOVA) and the Holm-Sidak post hoc test (α = 0.05). The results of total biomass quantification and metabolic activity revealed that the tyrosol promoted significant reductions (ranging from 22.32 to 86.16%) on single C. albicans and mixed cultures. Moreover, tyrosol at 200 mM and CHG significantly reduced (p < 0.05) the number of adhered cells to the acrylic surface for single and mixed cultures of both species, with reductions ranging from 1.74 to 3.64-log10. In conclusion, tyrosol has an inhibitory effect on Candida adhesion to acrylic resin, and further investigations are warranted to clarify its potential against Candida infections. PMID:26162470

  3. Effect of tyrosol on adhesion of Candida albicans and Candida glabrata to acrylic surfaces.

    PubMed

    Monteiro, Douglas Roberto; Feresin, Leonardo Perina; Arias, Laís Salomão; Barão, Valentim Adelino Ricardo; Barbosa, Debora Barros; Delbem, Alberto Carlos Botazzo

    2015-09-01

    The prevention of adhesion of Candida cells to acrylic surfaces can be regarded as an alternative to prevent denture stomatitis. The use of quorum sensing molecules, such as tyrosol, could potentially interfere with the adhesion process. Therefore, the aim of this study was to assess the effect of tyrosol on adhesion of single and mixed cultures of Candida albicans and Candida glabrata to acrylic resin surfaces. Tyrosol was diluted in each yeast inoculum (10(7) cells/ml in artificial saliva) at 25, 50, 100, and 200 mM. Then, each dilution was added to wells of 24-well plates containing the acrylic specimens, and the plates were incubated at 37°C for 2 h. After, the effect of tyrosol was determined by total biomass quantification, metabolic activity of the cells and colony-forming unit counting. Chlorhexidine gluconate (CHG) was used as a positive control. Data were analyzed using analysis of variance (ANOVA) and the Holm-Sidak post hoc test (α = 0.05). The results of total biomass quantification and metabolic activity revealed that the tyrosol promoted significant reductions (ranging from 22.32 to 86.16%) on single C. albicans and mixed cultures. Moreover, tyrosol at 200 mM and CHG significantly reduced (p < 0.05) the number of adhered cells to the acrylic surface for single and mixed cultures of both species, with reductions ranging from 1.74 to 3.64-log10. In conclusion, tyrosol has an inhibitory effect on Candida adhesion to acrylic resin, and further investigations are warranted to clarify its potential against Candida infections.

  4. The Candida genome database incorporates multiple Candida species: multispecies search and analysis tools with curated gene and protein information for Candida albicans and Candida glabrata.

    PubMed

    Inglis, Diane O; Arnaud, Martha B; Binkley, Jonathan; Shah, Prachi; Skrzypek, Marek S; Wymore, Farrell; Binkley, Gail; Miyasato, Stuart R; Simison, Matt; Sherlock, Gavin

    2012-01-01

    The Candida Genome Database (CGD, http://www.candidagenome.org/) is an internet-based resource that provides centralized access to genomic sequence data and manually curated functional information about genes and proteins of the fungal pathogen Candida albicans and other Candida species. As the scope of Candida research, and the number of sequenced strains and related species, has grown in recent years, the need for expanded genomic resources has also grown. To answer this need, CGD has expanded beyond storing data solely for C. albicans, now integrating data from multiple species. Herein we describe the incorporation of this multispecies information, which includes curated gene information and the reference sequence for C. glabrata, as well as orthology relationships that interconnect Locus Summary pages, allowing easy navigation between genes of C. albicans and C. glabrata. These orthology relationships are also used to predict GO annotations of their products. We have also added protein information pages that display domains, structural information and physicochemical properties; bibliographic pages highlighting important topic areas in Candida biology; and a laboratory strain lineage page that describes the lineage of commonly used laboratory strains. All of these data are freely available at http://www.candidagenome.org/. We welcome feedback from the research community at candida-curator@lists.stanford.edu.

  5. Gastrointestinal granuloma due to Candida albicans in an immunocompetent cat

    PubMed Central

    Duchaussoy, Anne-Claire; Rose, Annie; Talbot, Jessica J.; Barrs, Vanessa R.

    2015-01-01

    A 3.5 year-old cat was admitted to the University of Melbourne Veterinary Teaching Hospital for chronic vomiting. Abdominal ultrasonography revealed a focal, circumferential thickening of the wall of the duodenum extending from the pylorus aborally for 3 cm, and an enlarged gastric lymph node. Cytology of fine-needle aspirates of the intestinal mass and lymph node revealed an eosinophilic inflammatory infiltrate and numerous extracellular septate acute angle branching fungal-type hyphae. Occasional hyphae had globose terminal ends, as well as round to oval blastospores and germ tubes. Candida albicans was cultured from a surgical biopsy of the duodenal mass. No underlying host immunodeficiencies were identified. Passage of an abrasive intestinal foreign body was suspected to have caused intestinal mucosal damage resulting in focal intestinal candidiasis. The cat was treated with a short course of oral itraconazole and all clinical signs resolved. PMID:26862475

  6. Isolation and characterization of yeast monomorphic mutants of Candida albicans.

    PubMed Central

    Elorza, M V; Sentandreu, R; Ruiz-Herrera, J

    1994-01-01

    A method was devised for the isolation of yeast monomorphic (LEV) mutants of Candida albicans. By this procedure, about 20 stable yeast-like mutants were isolated after mutagenesis with ethyl methane sulfonate. The growth rate of the mutants in different carbon sources, both fermentable and not, was indistinguishable from that of the parental strain, but they were unable to grow as mycelial forms after application of any of the common effective inducers, i.e., heat shock, pH alterations, proline addition, or use of GlcNAc as the carbon source. Studies performed with one selected strain demonstrated that it had severe alterations in the chemical composition of the cell wall, mainly in the levels of chitin and glucans, and in specific mannoproteins, some of them recognizable by specific polyclonal and monoclonal antibodies. It is suggested that these structural alterations hinder the construction of a normal hyphal wall. Images PMID:8157600

  7. Ecology of Candida albicans gut colonization: inhibition of Candida adhesion, colonization, and dissemination from the gastrointestinal tract by bacterial antagonism.

    PubMed Central

    Kennedy, M J; Volz, P A

    1985-01-01

    Antibiotic-treated and untreated Syrian hamsters were inoculated intragastrically with Candida albicans to determine whether C. albicans could opportunistically colonize the gastrointestinal tract and disseminate to visceral organs. Antibiotic treatment decreased the total population levels of the indigenous bacterial flora and predisposed hamsters to gastrointestinal overgrowth and subsequent systemic dissemination by C. albicans in 86% of the animals. Both control hamsters not given antibiotics and antibiotic-treated animals reconventionalized with an indigenous microflora showed significantly lower gut populations of C. albicans, and C. albicans organisms were cultured from the visceral organs of 0 and 10% of the animals, respectively. Conversely, non-antibiotic-treated hamsters inoculated repeatedly with C. albicans had high numbers of C. albicans in the gut, and viable C. albicans was recovered from the visceral organs of 53% of the animals. Examination of the mucosal surfaces from test and control animals indicated further that animals which contained a complex indigenous microflora had significantly lower numbers of C. albicans associated with their gut walls than did antibiotic-treated animals. The ability of C. albicans to associate with intestinal mucosal surfaces also was tested by an in vitro adhesion assay. The results indicate that the indigenous microflora reduced the mucosal association of C. albicans by forming a dense layer of bacteria in the mucus gel, out-competing yeast cells for adhesion sites, and producing inhibitor substances (possibly volatile fatty acids, secondary bile acids, or both) that reduced C. albicans adhesion. It is suggested, therefore, that the indigenous intestinal microflora suppresses C. albicans colonization and dissemination from the gut by inhibiting Candida-mucosal association and reducing C. albicans population levels in the gut. Images PMID:3897061

  8. An Expanded Regulatory Network Temporally Controls Candida albicans Biofilm Formation

    PubMed Central

    Fox, Emily P.; Bui, Catherine K.; Nett, Jeniel E.; Hartooni, Nairi; Mui, Michael M.; Andes, David R.; Nobile, Clarissa J.; Johnson, Alexander D.

    2015-01-01

    Summary Candida albicans biofilms are composed of highly adherent and densely arranged cells with properties distinct from those of free-floating (planktonic) cells. These biofilms are a significant medical problem because they commonly form on implanted medical devices, are drug resistant, and are difficult to remove. C. albicans biofilms are not static structures; rather they are dynamic and develop over time. Here we characterize gene expression in biofilms during their development, and by comparing them to multiple planktonic reference states, we identify patterns of gene expression relevant to biofilm formation. In particular, we document time-dependent changes in genes involved in adhesion and metabolism, both of which are at the core of biofilm development. Additionally, we identify three new regulators of biofilm formation, Flo8, Gal4, and Rfx2, which play distinct roles during biofilm development over time. Flo8 is required for biofilm formation at all timepoints, and Gal4 and Rfx2 are needed for proper biofilm formation at intermediate time points. PMID:25784162

  9. Bacterial peptidoglycan-derived molecules activate Candida albicans hyphal growth.

    PubMed

    Wang, Yue; Xu, Xiao-Li

    2008-01-01

    Serum strongly induces the yeast-to-hypha growth transition in the human fungal pathogen Candida albicans, playing an important role in infection. However, identity of the serum inducer(s) and its sensor remain poorly defined. We used NMR to analyze the chromatographic serum fractionations enriched for the hypha-inducing activity and found structures resembling subunits of bacterial peptidoglycan (PGN). We then confirmed that several purified and synthetic muramyl dipeptides (MDPs), subunits of PGN, can indeed strongly promote C. albicans hyphal growth. Taking cue from the recognition of MDPs by the mammalian bacterial sensor Nod2 using its leucine-rich-repeat (LRR) domain, we discovered that MDPs activate the adenylyl cyclase Cyr1 by binding to its LRR domain. The cAMP/PKA signaling pathway is well known to control hyphal morphogenesis and other infection-related traits. Given the abundance of PGN at the large intestinal epithelial surface, a natural habitat and invasion site for C. albcians, our findings have important implications in the mechanisms of infection by this pathogen. PMID:19704871

  10. Bacterial peptidoglycan-derived molecules activate Candida albicans hyphal growth

    PubMed Central

    Xu, Xiao-Li

    2008-01-01

    Serum strongly induces the yeast-to-hypha growth transition in the human fungal pathogen Candida albicans, playing an important role in infection. However, identity of the serum inducer(s) and its sensor remain poorly defined. We used NMR to analyze the chromatographic serum fractionations enriched for the hypha-inducing activity and found structures resembling subunits of bacterial peptidoglycan (PGN). We then confirmed that several purified and synthetic muramyl dipeptides (MDPs), subunits of PGN, can indeed strongly promote C. albicans hyphal growth. Taking cue from the recognition of MDPs by the mammalian bacterial sensor Nod2 using its leucine-rich-repeat (LRR) domain, we discovered that MDPs activate the adenylyl cyclase Cyr1 by binding to its LRR domain. The cAMP/PKA signaling pathway is well known to control hyphal morphogenesis and other infection-related traits. Given the abundance of PGN at the large intestinal epithelial surface, a natural habitat and invasion site for C. albcians, our findings have important implications in the mechanisms of infection by this pathogen. PMID:19704871

  11. An expanded regulatory network temporally controls Candida albicans biofilm formation.

    PubMed

    Fox, Emily P; Bui, Catherine K; Nett, Jeniel E; Hartooni, Nairi; Mui, Michael C; Andes, David R; Nobile, Clarissa J; Johnson, Alexander D

    2015-06-01

    Candida albicans biofilms are composed of highly adherent and densely arranged cells with properties distinct from those of free-floating (planktonic) cells. These biofilms are a significant medical problem because they commonly form on implanted medical devices, are drug resistant and are difficult to remove. C. albicans biofilms are not static structures; rather they are dynamic and develop over time. Here we characterize gene expression in biofilms during their development, and by comparing them to multiple planktonic reference states, we identify patterns of gene expression relevant to biofilm formation. In particular, we document time-dependent changes in genes involved in adhesion and metabolism, both of which are at the core of biofilm development. Additionally, we identify three new regulators of biofilm formation, Flo8, Gal4, and Rfx2, which play distinct roles during biofilm development over time. Flo8 is required for biofilm formation at all time points, and Gal4 and Rfx2 are needed for proper biofilm formation at intermediate time points.

  12. Scolopendin 2 leads to cellular stress response in Candida albicans.

    PubMed

    Lee, Heejeong; Hwang, Jae-Sam; Lee, Dong Gun

    2016-07-01

    Centipedes, a kind of arthropod, have been reported to produce antimicrobial peptides as part of an innate immune response. Scolopendin 2 (AGLQFPVGRIGRLLRK) is a novel antimicrobial peptide derived from the body of the centipede Scolopendra subspinipes mutilans by using RNA sequencing. To investigate the intracellular responses induced by scolopendin 2, reactive oxygen species (ROS) and glutathione accumulation and lipid peroxidation were monitored over sublethal and lethal doses. Intracellular ROS and antioxidant molecule levels were elevated and lipids were peroxidized at sublethal concentrations. Moreover, the Ca(2+) released from the endoplasmic reticulum accumulated in the cytosol and mitochondria. These stress responses were considered to be associated with yeast apoptosis. Candida albicans cells exposed to scolopendin 2 were identified using diagnostic markers of apoptotic response. Various responses such as phosphatidylserine externalization, chromatin condensation, and nuclear fragmentation were exhibited. Scolopendin 2 disrupted the mitochondrial membrane potential and activated metacaspase, which was mediated by cytochrome c release. In conclusion, treatment of C. albicans with scolopendin 2 induced the apoptotic response at sublethal doses, which in turn led to mitochondrial dysfunction, metacaspase activation, and cell death. The cationic antimicrobial peptide scolopendin 2 from the centipede is a potential antifungal peptide, triggering the apoptotic response. PMID:27207682

  13. In Vitro Activity of Tea Tree Oil Vaginal Suppositories against Candida spp. and Probiotic Vaginal Microbiota.

    PubMed

    Di Vito, Maura; Mattarelli, Paola; Modesto, Monica; Girolamo, Antonietta; Ballardini, Milva; Tamburro, Annunziata; Meledandri, Marcello; Mondello, Francesca

    2015-10-01

    The aim of this work is to evaluate the in vitro microbicidal activity of vaginal suppositories (VS) containing tea tree oil (TTO-VS) towards Candida spp. and vaginal probiotics. A total of 20 Candida spp. strains, taken from patients with vaginitis and from an established type collection, including reference strains, were analysed by using the CLSI microdilution method. To study the action of VS towards the beneficial vaginal microbiota, the sensitivity of Bifidobacterium animalis subsp. lactis (DSM 10140) and Lactobacillus spp. (Lactobacillus casei R-215 and Lactobacillus acidophilus R-52) was tested. Both TTO-VS and TTO showed fungicidal activity against all strains of Candida spp. whereas placebo-VS or the Aloe gel used as controls were ineffective. The study of fractional fungicidal concentrations (FFC) showed synergistic interaction with the association between Amphotericin B and TTO (0.25 to 0.08 µg/ml, respectively) against Candida albicans. Instead, the probiotics were only affected by TTO concentration ≥ 4% v/v, while, at concentrations < 2% v/v, they remained viable. TTO-VS exhibits, in vitro, a selective fungicidal action, slightly affecting only the Bifidobacteriun animalis strain growth belonging to the vaginal microbiota. In vivo studies are needed to confirm the efficacy to prevent acute or recurrent vaginal candidiasis. PMID:26235937

  14. In Vitro Activity of Tea Tree Oil Vaginal Suppositories against Candida spp. and Probiotic Vaginal Microbiota.

    PubMed

    Di Vito, Maura; Mattarelli, Paola; Modesto, Monica; Girolamo, Antonietta; Ballardini, Milva; Tamburro, Annunziata; Meledandri, Marcello; Mondello, Francesca

    2015-10-01

    The aim of this work is to evaluate the in vitro microbicidal activity of vaginal suppositories (VS) containing tea tree oil (TTO-VS) towards Candida spp. and vaginal probiotics. A total of 20 Candida spp. strains, taken from patients with vaginitis and from an established type collection, including reference strains, were analysed by using the CLSI microdilution method. To study the action of VS towards the beneficial vaginal microbiota, the sensitivity of Bifidobacterium animalis subsp. lactis (DSM 10140) and Lactobacillus spp. (Lactobacillus casei R-215 and Lactobacillus acidophilus R-52) was tested. Both TTO-VS and TTO showed fungicidal activity against all strains of Candida spp. whereas placebo-VS or the Aloe gel used as controls were ineffective. The study of fractional fungicidal concentrations (FFC) showed synergistic interaction with the association between Amphotericin B and TTO (0.25 to 0.08 µg/ml, respectively) against Candida albicans. Instead, the probiotics were only affected by TTO concentration ≥ 4% v/v, while, at concentrations < 2% v/v, they remained viable. TTO-VS exhibits, in vitro, a selective fungicidal action, slightly affecting only the Bifidobacteriun animalis strain growth belonging to the vaginal microbiota. In vivo studies are needed to confirm the efficacy to prevent acute or recurrent vaginal candidiasis.

  15. Three prevacuolar compartment Rab GTPases impact Candida albicans hyphal growth.

    PubMed

    Johnston, Douglas A; Tapia, Arturo Luna; Eberle, Karen E; Palmer, Glen E

    2013-07-01

    Disruption of vacuolar biogenesis in the pathogenic yeast Candida albicans causes profound defects in polarized hyphal growth. However, the precise vacuolar pathways involved in yeast-hypha differentiation have not been determined. Previously we focused on Vps21p, a Rab GTPase involved in directing vacuolar trafficking through the late endosomal prevacuolar compartment (PVC). Herein, we identify two additional Vps21p-related GTPases, Ypt52p and Ypt53p, that colocalize with Vps21p and can suppress the hyphal defects of the vps21Δ/Δ mutant. Phenotypic analysis of gene deletion strains revealed that loss of both VPS21 and YPT52 causes synthetic defects in endocytic trafficking to the vacuole, as well as delivery of the virulence-associated vacuolar membrane protein Mlt1p from the Golgi compartment. Transcription of all three GTPase-encoding genes is increased under hyphal growth conditions, and overexpression of the transcription factor Ume6p is sufficient to increase the transcription of these genes. While only the vps21Δ/Δ single mutant has hyphal growth defects, these were greatly exacerbated in a vps21Δ/Δ ypt52Δ/Δ double mutant. On the basis of relative expression levels and phenotypic analysis of gene deletion strains, Vps21p is the most important of the three GTPases, followed by Ypt52p, while Ypt53p has an only marginal impact on C. albicans physiology. Finally, disruption of a nonendosomal AP-3-dependent vacuolar trafficking pathway in the vps21Δ/Δ ypt52Δ/Δ mutant, further exacerbated the stress and hyphal growth defects. These findings underscore the importance of membrane trafficking through the PVC in sustaining the invasive hyphal growth form of C. albicans.

  16. Development of a High-Throughput Candida albicans Biofilm Chip

    PubMed Central

    Srinivasan, Anand; Uppuluri, Priya; Lopez-Ribot, Jose; Ramasubramanian, Anand K.

    2011-01-01

    We have developed a high-density microarray platform consisting of nano-biofilms of Candida albicans. A robotic microarrayer was used to print yeast cells of C. albicans encapsulated in a collagen matrix at a volume as low as 50 nL onto surface-modified microscope slides. Upon incubation, the cells grow into fully formed “nano-biofilms”. The morphological and architectural complexity of these biofilms were evaluated by scanning electron and confocal scanning laser microscopy. The extent of biofilm formation was determined using a microarray scanner from changes in fluorescence intensities due to FUN 1 metabolic processing. This staining technique was also adapted for antifungal susceptibility testing, which demonstrated that, similar to regular biofilms, cells within the on-chip biofilms displayed elevated levels of resistance against antifungal agents (fluconazole and amphotericin B). Thus, results from structural analyses and antifungal susceptibility testing indicated that despite miniaturization, these biofilms display the typical phenotypic properties associated with the biofilm mode of growth. In its final format, the C. albicans biofilm chip (CaBChip) is composed of 768 equivalent and spatially distinct nano-biofilms on a single slide; multiple chips can be printed and processed simultaneously. Compared to current methods for the formation of microbial biofilms, namely the 96-well microtiter plate model, this fungal biofilm chip has advantages in terms of miniaturization and automation, which combine to cut reagent use and analysis time, minimize labor intensive steps, and dramatically reduce assay costs. Such a chip should accelerate the antifungal drug discovery process by enabling rapid, convenient and inexpensive screening of hundreds-to-thousands of compounds simultaneously. PMID:21544190

  17. Early detection of Candida albicans biofilms at porous electrodes.

    PubMed

    Congdon, Robert B; Feldberg, Alexander S; Ben-Yakar, Natalie; McGee, Dennis; Ober, Christopher; Sammakia, Bahgat; Sadik, Omowunmi A

    2013-02-15

    We describe the development of an electrochemical sensor for early detection of biofilm using Candida albicans. The electrochemical sensor used the ability of biofilms to accept electrons from redox mediators relative to the number of metabolically active cells present. Cyclic voltammetry and differential pulse voltammetry techniques were used to monitor the redox reaction of K(3)Fe(CN)(6) at porous reticulated vitreous carbon (RVC) (238.7 cm(2)) working electrodes versus Ag/AgCl reference. A shift in the peak potential occurred after 12 h of film growth, which is attributed to the presence of C. albicans. Moreover, the intensity of the ferricyanide reduction peak first increased as C. albicans deposited onto the porous electrodes at various growth times. The peak current subsequently decreased at extended periods of growth of 48 h. The reduction in peak current was attributed to the biofilm reaching its maximum growth thickness, which correlated with the maximum number of metabolically active cells. The observed diffusion coefficients for the bare RVC and biofilm-coated electrodes were 2.2 × 10(-3) and 7.0 × 10(-6) cm(2)/s, respectively. The increase in diffusivity from the bare electrode to the biofilm-coated electrode indicated some enhancement of electron transfer mediated by the biofilm to the porous electrode. Verification of the growth of biofilm was achieved using scanning electron microcopy and laser scanning confocal imaging microscopy. Validation with conventional plating techniques confirmed that the correlation (R(2) = 0.9392) could be achieved between the electrochemical sensors data and colony-forming units. PMID:23107627

  18. Miltefosine is effective against Candida albicans and Fusarium oxysporum nail biofilms in vitro.

    PubMed

    Machado Vila, Taissa Vieira; Sousa Quintanilha, Natália; Rozental, Sonia

    2015-11-01

    Onychomycosis is a fungal nail infection that represents ∼50 % of all nail disease cases worldwide. Clinical treatment with standard antifungals frequently requires long-term systemic therapy to avoid chronic disease. Onychomycosis caused by non-dermatophyte moulds, such as Fusarium spp., and yeasts, such as Candida spp., is particularly difficult to treat, possibly due to the formation of drug-resistant fungal biofilms on affected areas. Here, we show that the alkylphospholipid miltefosine, used clinically against leishmaniasis and cutaneous breast metastases, has potent activity against biofilms of Fusarium oxysporum and Candida albicans formed on human nail fragments in vitro. Miltefosine activity was compared with that of commercially available antifungals in the treatment of biofilms at two distinct developmental phases: formation and maturation (pre-formed biofilms). Drug activity towards biofilms formed on nail fragments and on microplate surfaces (microdilution assays) was evaluated using XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] assays, and drug effects on fingernail biofilms were analysed by scanning electron microscopy (SEM). For F. oxysporum, miltefosine at 8 μg ml- 1 inhibited biofilm formation by 93%, whilst 256 μg ml- 1 reduced the metabolic activity of pre-formed nail biofilms by 93%. Treatment with miltefosine at 1000 μg ml- 1 inhibited biofilm formation by 89% and reduced the metabolic activity of pre-formed C. albicans biofilms by 99%. SEM analyses of biofilms formed on fingernail fragments showed a clear reduction in biofilm biomass after miltefosine treatment, in agreement with XTT results. Our results show that miltefosine has potential as a therapeutic agent against onychomycosis and should be considered for in vivo efficacy studies, especially in topical formulations for refractory disease treatment. PMID:26404553

  19. Miltefosine is effective against Candida albicans and Fusarium oxysporum nail biofilms in vitro.

    PubMed

    Machado Vila, Taissa Vieira; Sousa Quintanilha, Natália; Rozental, Sonia

    2015-11-01

    Onychomycosis is a fungal nail infection that represents ∼50 % of all nail disease cases worldwide. Clinical treatment with standard antifungals frequently requires long-term systemic therapy to avoid chronic disease. Onychomycosis caused by non-dermatophyte moulds, such as Fusarium spp., and yeasts, such as Candida spp., is particularly difficult to treat, possibly due to the formation of drug-resistant fungal biofilms on affected areas. Here, we show that the alkylphospholipid miltefosine, used clinically against leishmaniasis and cutaneous breast metastases, has potent activity against biofilms of Fusarium oxysporum and Candida albicans formed on human nail fragments in vitro. Miltefosine activity was compared with that of commercially available antifungals in the treatment of biofilms at two distinct developmental phases: formation and maturation (pre-formed biofilms). Drug activity towards biofilms formed on nail fragments and on microplate surfaces (microdilution assays) was evaluated using XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] assays, and drug effects on fingernail biofilms were analysed by scanning electron microscopy (SEM). For F. oxysporum, miltefosine at 8 μg ml- 1 inhibited biofilm formation by 93%, whilst 256 μg ml- 1 reduced the metabolic activity of pre-formed nail biofilms by 93%. Treatment with miltefosine at 1000 μg ml- 1 inhibited biofilm formation by 89% and reduced the metabolic activity of pre-formed C. albicans biofilms by 99%. SEM analyses of biofilms formed on fingernail fragments showed a clear reduction in biofilm biomass after miltefosine treatment, in agreement with XTT results. Our results show that miltefosine has potential as a therapeutic agent against onychomycosis and should be considered for in vivo efficacy studies, especially in topical formulations for refractory disease treatment.

  20. Comparison of the in vitro activity of echinocandins against Candida albicans, Candida dubliniensis, and Candida africana by time-kill curves.

    PubMed

    Gil-Alonso, Sandra; Jauregizar, Nerea; Cantón, Emilia; Eraso, Elena; Quindós, Guillermo

    2015-05-01

    Candida albicans remains the most common fungal pathogen. This species is closely related to 2 phenotypically similar cryptic species, Candida dubliniensis and Candida africana. This study aims to compare the antifungal activities of echinocandins against 7 C. albicans, 5 C. dubliniensis, and 2 C. africana strains by time-kill methodology. MIC values were similar for the 3 species; however, differences in killing activity were observed among species, isolates, and echinocandins. Echinocandins produced weak killing activity against the 3 species. In all drugs, the fungicidal endpoint (99.9% mortality) was reached at ≤31 h with ≥0.5 μg/mL for anidulafungin in 4 C. albicans and 1 C. dubliniensis, for caspofungin in 1 C. albicans and 2 C. dubliniensis, and for micafungin in 4 C. albicans and 1 C. dubliniensis. None of echinocandins showed lethality against C. africana. Identification of these new cryptic species and time-kill studies would be recommendable when echinocandin treatment fails.

  1. A patient with allergic bronchopulmonary mycosis caused by Aspergillus fumigatus and Candida albicans.

    PubMed

    Wardhana; Datau, E A

    2012-10-01

    Allergic Bronchopulmonary Mycosis (ABPM) is an exagregated immunologic response to fungal colonization in the lower airways. It may cause by many kinds of fungal, but Aspergillus fumigatus is the most common cause of ABPM, although other Aspergillus and other fungal organisms, like Candida albicans, have been implicated. Aspergllus fumigatus and Candida albicans may be found as outdoor and indoor fungi, and cause the sensitization, elicitation of the disease pathology, and its clinical manifestations. Several diagnostic procedurs may be impicated to support the diagnosis of ABPM caused by Aspergillus fumigatus and Candida albicans. A case of allergic bronchopulmonary mycosis caused by Aspergillus fumigatus and Candida albicans in a 48 year old man was discussed. The patient was treated with antifungal, corticosteroids, and antibiotic for the secondary bacterial infection. The patient's condition is improved without any significant side effects. PMID:23314973

  2. The immune response against Candida spp. and Sporothrix schenckii.

    PubMed

    Martínez-Álvarez, José A; Pérez-García, Luis A; Flores-Carreón, Arturo; Mora-Montes, Héctor M

    2014-01-01

    Candida albicans is the main causative agent of systemic candidiasis, a condition with high mortality rates. The study of the interaction between C. albicans and immune system components has been thoroughly studied and nowadays there is a model for the anti-C. albicans immune response; however, little is known about the sensing of other pathogenic species of the Candida genus. Sporothrix schenckii is the causative agent of sporotrichosis, a subcutaneous mycosis, and thus far there is limited information about its interaction with the immune system. In this paper, we review the most recent information about the immune sensing of species from genus Candida and S. schenckii. Thoroughly searches in scientific journal databases were performed, looking for papers addressing either Candida- or Sporothrix-immune system interactions. There is a significant advance in the knowledge of non-C. albicans species of Candida and Sporothrix immune sensing; however, there are still relevant points to address, such as the specific contribution of pathogen-associated molecular patterns (PAMPs) for sensing by different immune cells and the immune receptors involved in such interactions. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012).

  3. In vitro activity of essential oils extracted from plants used as spices against fluconazole-resistant and fluconazole-susceptible Candida spp.

    PubMed

    Pozzatti, Patrícia; Scheid, Liliane Alves; Spader, Tatiana Borba; Atayde, Margareth Linde; Santurio, Janio Morais; Alves, Sydney Hartz

    2008-11-01

    In the present study, the antifungal activity of selected essential oils obtained from plants used as spices was evaluated against both fluconazole-resistant and fluconazole-susceptible Candida spp. The Candida species studied were Candida albicans, Candida dubliniensis, Candida tropicalis, Candida glabrata, and Candida krusei. For comparison purposes, they were arranged in groups as C. albicans, C. dubliniensis, and Candida non-albicans. The essential oils were obtained from Cinnamomum zeylanicum Breyn, Lippia graveolens HBK, Ocimum basilicum L., Origanum vulgare L., Rosmarinus officinalis L., Salvia officinalis L., Thymus vulgaris L., and Zingiber officinale. The susceptibility tests were based on the M27-A2 methodology. The chemical composition of the essential oils was obtained by gas chromatography-mass spectroscopy and by retention indices. The results showed that cinnamon, Mexican oregano, oregano, thyme, and ginger essential oils have different levels of antifungal activity. Oregano and ginger essential oils were found to be the most and the least efficient, respectively. The main finding was that the susceptibilities of fluconazole-resistant C. albicans, C. dubliniensis, and Candida non-albicans to Mexican oregano, oregano, thyme, and ginger essential oils were higher than those of the fluconazole-susceptible yeasts (P<0.05). In contrast, fluconazole-resistant C. albicans and Candida non-albicans were less susceptible to cinnamon essential oil than their fluconazole-susceptible counterparts (P<0.05). A relationship between the yeasts' susceptibilities and the chemical composition of the essential oils studied was apparent when these 2 parameters were compared. Finally, basil, rosemary, and sage essential oils did not show antifungal activity against Candida isolates at the tested concentrations. PMID:18997851

  4. Investigation of minor species Candida africana, Candida stellatoidea and Candida dubliniensis in the Candida albicans complex among Yaoundé (Cameroon) HIV-infected patients.

    PubMed

    Ngouana, Thierry K; Krasteva, Donika; Drakulovski, Pascal; Toghueo, Rufin K; Kouanfack, Charles; Ambe, Akaba; Reynes, Jacques; Delaporte, Eric; Boyom, Fabrice F; Mallié, Michèle; Bertout, Sébastien

    2015-01-01

    Minor species of the Candida albicans complex may cause overestimation of the epidemiology of C. albicans, and misidentifications could mask their implication in human pathology. Authors determined the occurrence of minor species of the C. albicans complex (C. africana, C. dubliniensis and C. stellatoidea) among Yaoundé HIV-infected patients, Cameroon. Stool, vaginal discharge, urine and oropharyngeal samples were analysed by mycological diagnosis. Isolates were identified by conventional methods and mass spectrometry (MS; carried out by the matrix-assisted laser desorption-ionisation time-of-flight MS protocol). Candida albicans isolates were thereafter submitted to the PCR amplification of the Hwp1 gene. The susceptibility of isolates to antifungal drugs was tested using the Clinical and Laboratory Standards Institute M27-A3 protocol. From 115 C. albicans obtained isolates, neither C. dubliniensis nor C. stellatoidea was observed; two strains of C. africana (422PV and 448PV) were identified by PCR electrophoretic profiles at 700 bp. These two C. africana strains were vaginal isolates. The isolate 448PV was resistant to ketoconazole at the minimal inhibitory concentration of 2 μg ml(-1), and showed reduced susceptibility to amphotericin B at 1 μg ml(-1). This first report on C. africana occurrence in Cameroon brings clues for the understanding of the global epidemiology of this yeast as well as that of minor species of the C. albicans complex.

  5. Manipulation of host diet to reduce gastrointestinal colonization by the opportunistic pathogen Candida albicans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Candida albicans, the most common human fungal pathogen, can cause systemic infections with a mortality rate of ~40%. Infections arise from colonization of the gastrointestinal (GI) tract, where C. albicans is part of the normal microflora. Reducing colonization in at-risk patients using antifungal ...

  6. [Meningitis to Candida albicans at the adult, use of the new diagnosis methods].

    PubMed

    Duclos, G; Dumont, J-C; Ranque, S; Zieleskiewicz, L; Bruder, N

    2014-01-01

    Candida albicans or non-albicans are a frequent source of infection but seldom displayed in cerebrospinal fluid although responsible of an important number of nosocomial meningitis. Diagnosis is difficult which often delays treatment, which in turn hinders prognostic. This clinical case shows a patient afflicted with a deadly C. albicans meningitis and allows us to focus on new diagnostic tools and advice against this infection. PMID:25127852

  7. [Isolation of Candida spp. from ascites in cirrhotic patients].

    PubMed

    Saludes, Paula; Araguás, Cristina; Sánchez-Delgado, Jordi; Dalmau, Blai; Font, Bernat

    2016-10-01

    The isolation of Candida spp. in ascites of cirrhotic patients is an uncommon situation in clinical practice. Factors that have been associated with increased susceptibility to primary fungal peritonitis are exposure to broad-spectrum antibiotics and immunosuppression, a typical situation of these patients. We report seven episodes of Candida spp. isolation in ascites of cirrhotic patients detected in our hospital during the past 15years.

  8. A piglet model for studying Candida albicans colonization of the human oro-gastrointestinal tract.

    PubMed

    Hoeflinger, Jennifer L; Coleman, David A; Oh, Soon-Hwan; Miller, Michael J; Hoyer, Lois L

    2014-08-01

    Pigs from a variety of sources were surveyed for oro-gastrointestinal (oro-GIT) carriage of Candida albicans. Candida albicans-positive animals were readily located, but we also identified C. albicans-free pigs. We hypothesized that pigs could be stably colonized with a C. albicans strain of choice, simply by feeding yeast cells. Piglets were farrowed routinely and remained with the sow for 4 days to acquire a normal microbiota. Piglets were then placed in an artificial rearing environment and fed sow milk replacer. Piglets were inoculated orally with one of three different C. albicans strains. Piglets were weighed daily, and culture swabs were collected to detect C. albicans orally, rectally and in the piglet's environment. Stable C. albicans colonization over the course of the study did not affect piglet growth. Necropsy revealed mucosally associated C. albicans throughout the oro-GIT with the highest abundance in the esophagus. Uninoculated control piglets remained C. albicans-negative. These data establish the piglet as a model to study C. albicans colonization of the human oro-GIT. Similarities between oro-GIT colonization in humans and pigs, as well as the ease of working with the piglet model, suggest its adaptability for use among investigators interested in understanding C. albicans-host commensal interactions.

  9. Vaginal lactobacilli as potential probiotics against Candida SPP.

    PubMed Central

    Gil1, Natalia F.; Martinez, Rafael C.R.; Gomes, Bruna C.; Nomizo, Auro; De Martinis, Elaine C. P.

    2010-01-01

    Urogenital infections affect millions of people every year worldwide. The treatment of these diseases usually requires the use of antimicrobial agents, and more recently, the use of probiotic lactic acid bacteria (LAB) cultures for the management of vaginal infections has been extensively studied. In this work, 11 vaginal lactobacilli isolates, previously obtained from healthy patients, were studied to screen microorganisms with probiotic properties against Candida spp. The LAB were tested for their ability of auto-aggregation, co-aggregation with C. albicans, C. glabrata, C. krusei, and C. tropicalis, adhesion to Caco-2 epithelial cells and production of lactic acid and hydrogen peroxide (H2O2). All lactobacilli isolates tested were able to auto-aggregate (ranging from 25.3% to 75.4% assessed at 4 hours of incubation) and to co-aggregate with the four Candida species into different degrees; among them L. crispatus showed the highest scores of co-aggregation. The highest amount of lactic acid was produced by L. salivarius (13.9 g/l), followed by L. johnsonii (6.5 g/l), L. acidophilus (5.5 g/l), and L. jensenii (5.4 g/l). All isolates produced H2O2, but the highest levels (3 – 10 mg/l) were observed for L. acidophilus, L. crispatus, L. gasseri, L. johnsonii, and L. vaginalis. Only L. agilis, L. jensenii, L. johnsonii and L. ruminus were able to adhere to epithelial Caco-2 cells. Among the isolates evaluated, L agilis, L. jensenii, L. johnsonii, and L. ruminus exhibited simultaneously several desirable properties as potential probiotic strains justifying future studies to evaluate their technological properties in different pharmaceutical preparations for human use. PMID:24031455

  10. The Fungus Candida albicans Tolerates Ambiguity at Multiple Codons

    PubMed Central

    Simões, João; Bezerra, Ana R.; Moura, Gabriela R.; Araújo, Hugo; Gut, Ivo; Bayes, Mónica; Santos, Manuel A. S.

    2016-01-01

    The ascomycete Candida albicans is a normal resident of the gastrointestinal tract of humans and other warm-blooded animals. It occurs in a broad range of body sites and has high capacity to survive and proliferate in adverse environments with drastic changes in oxygen, carbon dioxide, pH, osmolarity, nutrients, and temperature. Its biology is unique due to flexible reassignment of the leucine CUG codon to serine and synthesis of statistical proteins. Under standard growth conditions, CUG sites incorporate leucine (3% of the times) and serine (97% of the times) on a proteome wide scale, but leucine incorporation fluctuates in response to environmental stressors and can be artificially increased up to 98%. In order to determine whether such flexibility also exists at other codons, we have constructed several serine tRNAs that decode various non-cognate codons. Expression of these tRNAs had minor effects on fitness, but growth of the mistranslating strains at different temperatures, in medium with different pH and nutrients composition was often enhanced relatively to the wild type (WT) strain, supporting our previous data on adaptive roles of CUG ambiguity in variable growth conditions. Parallel evolution of the recombinant strains (100 generations) followed by full genome resequencing identified various strain specific single nucleotide polymorphisms (SNP) and one SNP in the deneddylase (JAB1) gene in all strains. Since JAB1 is a subunit of the COP9 signalosome complex, which interacts with cullin (Cdc53p) to mediate degradation of a variety of cellular proteins, our data suggest that neddylation plays a key role in tolerance and adaptation to codon ambiguity in C. albicans. PMID:27065968

  11. Susceptibility of Candida albicans to new synthetic sulfone derivatives.

    PubMed

    Staniszewska, Monika; Bondaryk, Małgorzata; Ochal, Zbigniew

    2015-02-01

    The influence of halogenated methyl sulfones, i.e. bromodichloromethyl-4-chloro-3-nitrophenyl sulfone (named halogenated methyl sulfone 1), dichloromethyl-4-chloro-3-nitrophenyl sulfone (halogenated methyl sulfone 2), and chlorodibromomethyl-4-hydrazino-3-nitrophenyl sulfone (halogenated methyl sulfone 3), on cell growth inhibition, aspartic protease gene (SAP4-6) expression, adhesion to epithelium, and filamentation was investigated. Antifungal susceptibility of the halogenated methyl sulfones was determined with the M27-A3 protocol in the range of 16-0.0313 µg/mL. Adherence to Caco-2 cells was performed in 24-well plates; relative quantification was normalized against ACT1 in cells after 18 h of growth in YEPD and on Caco-2 cells. SAP4-6 expression was analyzed using RT-PCR. Structure-activity relationship studies suggested that halogenated methyl sulfone 1 containing bromodichloromethyl or dichloromethyl function at C-4 (halogenated methyl sulfone 2) of the phenyl ring showed the best activity (100% cell inhibition at 0.5 µg/mL), while hydrazine at C-1 (halogenated methyl sulfone 3) reduced the sulfone potential (100% = 4 µg/mL). SAP4-6 were up- or down-regulated depending on the strains' genetic background and the substitutions on the phenyl ring. Halogenated methyl sulfone 2 repressed germination and affected adherence to epithelium (P ≤ 0.05). The tested halogenated methyl sulfones interfered with the adhesion of Candida albicans cells to the epithelial tissues, without affecting their viability after 90 min of incubation. The mode of action of the halogenated methyl sulfones was attributed to the reduced virulence of C. albicans. SAP5 and SAP6 contribute to halogenated methyl sulfones resistance. Thus, halogenated methyl sulfones can inhibit biofilm formation due to their interference with adherence and with the yeast-to-hyphae transition.

  12. Function and Regulation of Cph2 in Candida albicans

    PubMed Central

    Lane, Shelley; Di Lena, Pietro; Tormanen, Kati; Baldi, Pierre

    2015-01-01

    Candida albicans is associated with humans as both a harmless commensal organism and a pathogen. Cph2 is a transcription factor whose DNA binding domain is similar to that of mammalian sterol response element binding proteins (SREBPs). SREBPs are master regulators of cellular cholesterol levels and are highly conserved from fungi to mammals. However, ergosterol biosynthesis is regulated by the zinc finger transcription factor Upc2 in C. albicans and several other yeasts. Cph2 is not necessary for ergosterol biosynthesis but is important for colonization in the murine gastrointestinal (GI) tract. Here we demonstrate that Cph2 is a membrane-associated transcription factor that is processed to release the N-terminal DNA binding domain like SREBPs, but its cleavage is not regulated by cellular levels of ergosterol or oxygen. Chromatin immunoprecipitation sequencing (ChIP-seq) shows that Cph2 binds to the promoters of HMS1 and other components of the regulatory circuit for GI tract colonization. In addition, 50% of Cph2 targets are also bound by Hms1 and other factors of the regulatory circuit. Several common targets function at the head of the glycolysis pathway. Thus, Cph2 is an integral part of the regulatory circuit for GI colonization that regulates glycolytic flux. Transcriptome sequencing (RNA-seq) shows a significant overlap in genes differentially regulated by Cph2 and hypoxia, and Cph2 is important for optimal expression of some hypoxia-responsive genes in glycolysis and the citric acid cycle. We suggest that Cph2 and Upc2 regulate hypoxia-responsive expression in different pathways, consistent with a synthetic lethal defect of the cph2 upc2 double mutant in hypoxia. PMID:26342020

  13. Humoral Immunity Links Candida albicans Infection and Celiac Disease

    PubMed Central

    Fradin, Chantal; Salleron, Julia; Damiens, Sébastien; Moragues, Maria Dolores; Souplet, Vianney; Jouault, Thierry; Robert, Raymond; Dubucquoi, Sylvain; Sendid, Boualem; Colombel, Jean Fréderic; Poulain, Daniel

    2015-01-01

    Objective The protein Hwp1, expressed on the pathogenic phase of Candida albicans, presents sequence analogy with the gluten protein gliadin and is also a substrate for transglutaminase. This had led to the suggestion that C. albicans infection (CI) may be a triggering factor for Celiac disease (CeD) onset. We investigated cross-immune reactivity between CeD and CI. Methods Serum IgG levels against recombinant Hwp1 and serological markers of CeD were measured in 87 CeD patients, 41 CI patients, and 98 healthy controls (HC). IgA and IgG were also measured in 20 individuals from each of these groups using microchips sensitized with 38 peptides designed from the N-terminal of Hwp1. Results CI and CeD patients had higher levels of anti-Hwp1 (p=0.0005 and p=0.004) and anti-gliadin (p=0.002 and p=0.0009) antibodies than HC but there was no significant difference between CeD and CI patients. CeD and CI patients had higher levels of anti-transglutaminase IgA than HC (p=0.0001 and p=0.0039). During CI, the increase in anti-Hwp1 paralleled the increase in anti-gliadin antibodies. Microchip analysis showed that CeD patients were more reactive against some Hwp1 peptides than CI patients, and that some deamidated peptides were more reactive than their native analogs. Binding of IgG from CeD patients to Hwp1 peptides was inhibited by γIII gliadin peptides. Conclusions Humoral cross-reactivity between Hwp1 and gliadin was observed during CeD and CI. Increased reactivity to Hwp1 deamidated peptide suggests that transglutaminase is involved in this interplay. These results support the hypothesis that CI may trigger CeD onset in genetically-susceptible individuals. PMID:25793717

  14. Functional characterization of Candida albicans Hos2 histone deacetylase

    PubMed Central

    Karthikeyan, G; Paul-Satyaseela, Maneesh; Dhatchana Moorthy, Nachiappan; Gopalaswamy, Radha; Narayanan, Shridhar

    2014-01-01

    Candida albicans is a mucosal commensal organism capable of causing superficial (oral and vaginal thrush) infections in immune normal hosts, but is a major pathogen causing systemic and mucosal infections in immunocompromised individuals. Azoles have been very effective anti-fungal agents and the mainstay in treating opportunistic mold and yeast infections. Azole resistant strains have emerged compromising the utility of this class of drugs. It has been shown that azole resistance can be reversed by the co-administration of a histone deacetylase (HDAC) inhibitor, suggesting that resistance is mediated by epigenetic mechanisms possibly involving Hos2, a fungal deacetylase. We report here the cloning and functional characterization of  HOS2 (High Osmolarity  Sensitive) , a gene coding for fungal histone deacetylase from  C. albicans. Inhibition studies showed that Hos2 is susceptible to pan inhibitors such as trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA), but is not inhibited by class I inhibitors such as MS-275. This  in  vitro enzymatic assay, which is amenable to high throughput could be used for screening potent fungal Hos2 inhibitors that could be a potential anti-fungal adjuvant. Purified Hos2 protein consistently deacetylated tubulins, rather than histones from TSA-treated cells. Hos2 has been reported to be a putative NAD+ dependent histone deacetylase, a feature of sirtuins. We assayed for sirtuin activation with resveratrol and purified Hos2 protein and did not find any sirtuin activity. PMID:25110576

  15. Sampling of Candida albicans and Candida tropicalis by Langerin-positive dendritic cells in mouse Peyer's patches.

    PubMed

    De Jesus, Magdia; Rodriguez, Adam E; Yagita, Hideo; Ostroff, Gary R; Mantis, Nicholas J

    2015-11-01

    Members of the Candida genus, including C. albicans and C. tropicalis are opportunistic fungal pathogens that are increasingly associated with gastrointestinal infections and inflammatory bowel diseases. In healthy populations, however, C. albicans and C. tropicalis are considered benign members of the mycobiome, and are presumably kept in check by the mucosal immune system. In this study, we demonstrate in mice that C. albicans and C. tropicalis are sampled by Peyer's patch (PP) dendritic cells (DCs). Uptake into gut-associated lymphoid tissues occurred rapidly and was at least partly M cell-dependent. C. albicans and C. tropicalis preferentially localized in (and persisted within) a recently identified sub- population of Peyer's patch DCs distinguished by their expression of the C-type lectin receptor, Langerin. This study is the first to identify a subset of PP DCs capable of sampling Candida species.

  16. Morphological and physiological changes induced by contact-dependent interaction between Candida albicans and Fusobacterium nucleatum.

    PubMed

    Bor, Batbileg; Cen, Lujia; Agnello, Melissa; Shi, Wenyuan; He, Xuesong

    2016-01-01

    Candida albicans and Fusobacterium nucleatum are well-studied oral commensal microbes with pathogenic potential that are involved in various oral polymicrobial infectious diseases. Recently, we demonstrated that F. nucleatum ATCC 23726 coaggregates with C. albicans SN152, a process mainly mediated by fusobacterial membrane protein RadD and Candida cell wall protein Flo9. The aim of this study was to investigate the potential biological impact of this inter-kingdom interaction. We found that F. nucleatum ATCC 23726 inhibits growth and hyphal morphogenesis of C. albicans SN152 in a contact-dependent manner. Further analysis revealed that the inhibition of Candida hyphal morphogenesis is mediated via RadD and Flo9 protein pair. Using a murine macrophage cell line, we showed that the F. nucleatum-induced inhibition of Candida hyphal morphogenesis promotes C. albicans survival and negatively impacts the macrophage-killing capability of C. albicans. Furthermore, the yeast form of C. albicans repressed F. nucleatum-induced MCP-1 and TNFα production in macrophages. Our study suggests that the interaction between C. albicans and F. nucleatum leads to a mutual attenuation of virulence, which may function to promote a long-term commensal lifestyle within the oral cavity. This finding has significant implications for our understanding of inter-kingdom interaction and may impact clinical treatment strategies. PMID:27295972

  17. Morphological and physiological changes induced by contact-dependent interaction between Candida albicans and Fusobacterium nucleatum

    PubMed Central

    Bor, Batbileg; Cen, Lujia; Agnello, Melissa; Shi, Wenyuan; He, Xuesong

    2016-01-01

    Candida albicans and Fusobacterium nucleatum are well-studied oral commensal microbes with pathogenic potential that are involved in various oral polymicrobial infectious diseases. Recently, we demonstrated that F. nucleatum ATCC 23726 coaggregates with C. albicans SN152, a process mainly mediated by fusobacterial membrane protein RadD and Candida cell wall protein Flo9. The aim of this study was to investigate the potential biological impact of this inter-kingdom interaction. We found that F. nucleatum ATCC 23726 inhibits growth and hyphal morphogenesis of C. albicans SN152 in a contact-dependent manner. Further analysis revealed that the inhibition of Candida hyphal morphogenesis is mediated via RadD and Flo9 protein pair. Using a murine macrophage cell line, we showed that the F. nucleatum-induced inhibition of Candida hyphal morphogenesis promotes C. albicans survival and negatively impacts the macrophage-killing capability of C. albicans. Furthermore, the yeast form of C. albicans repressed F. nucleatum-induced MCP-1 and TNFα production in macrophages. Our study suggests that the interaction between C. albicans and F. nucleatum leads to a mutual attenuation of virulence, which may function to promote a long-term commensal lifestyle within the oral cavity. This finding has significant implications for our understanding of inter-kingdom interaction and may impact clinical treatment strategies. PMID:27295972

  18. Effect of Low-Level Laser therapy on the fungal proliferation of Candida albicans

    NASA Astrophysics Data System (ADS)

    Carneiro, Vanda S. M.; Araújo, Natália C.; Menezes, Rebeca F. d.; Moreno, Lara M.; Santos-Neto, Alexandrino d. P.; Gerbi, Marleny Elizabeth M.

    2016-03-01

    Candida albicans plays an important role in triggering infections in HIV+ patients. The indiscriminate use of antifungals has led to resistance to Candida albicans, which requires new treatment alternatives for oral candidiasis. Low-level laser therapy promotes a considerable improvement in the healing of wounds and in curing illnesses caused by microorganisms. The aim of the present study was to assess the effect of laser radiation on the cell proliferation of Candida albicans in immunosuppressed patients. Six Candida albicans strains that had been isolated from immunosuppressed patients were divided into a control group and experimental groups, which received eight sessions of laser therapy (InGaAlP, λ685nm, P = 30mW, CW, Φ~6 mm and GaAlAs, λ830nm, P = 40mW, CW, Φ~6 mm) using dosimetries of 6J/cm2, 8J/cm2, 10J/cm2 and 12J/cm2 for each wavelength and power. The results were not statistically significant (Kruskal Wallis, p > 0.05), although the proliferation of Candida albicans was lower in some of the experimental groups. The dosimetry of 6J/cm2 (GaAlAs, λ830nm, P = 40mW) provided lower mean scores than the other groups for the growth of Candida. Further studies are required to confirm whetehr laser therapy is a viable option in the treatment of fungal infections.

  19. Association of Oral Candida albicans with Severe Early Childhood Caries - A Pilot Study

    PubMed Central

    Thomas, Ann; Mhambrey, Sanjana; Chokshi, Achala; Jana, Sinjana; Thakur, Sneha; Jose, Deepak; Bajpai, Garima

    2016-01-01

    Introduction In early childhood, children are more susceptible to opportunistic microbial colonization in the oral cavity due to immature immune system and not fully established micro flora. The current literature proposes a probable role of Candida albicans, a fungus in the etiopathogenesis of dental caries. Aim This study was conducted to compare the Candida albicans count in children with severe early childhood caries and caries free children. Materials and Methods A cross-sectional study was conducted in 40 randomly selected healthy children between 12 to 71 months of age, who were divided into two groups based on the caries experience as Severe Early Childhood Caries (SECC) (dmfs ≥4) and caries free (dmfs = 0). The caries experiences (dmfs index) of the 40 children were recorded using visible light and diagnostic instruments. A 2ml sample of unstimulated whole saliva collected from the children was transported to the microbiology laboratory in universal containers and evaluated for Candida albicans count using the selective media. The data was statistically analyzed using SPSS software 17.0. Results Candida albicans was found in both the SECC group and caries free group. Median Candida albicans of the SECC group was numerically greater than the caries free group and this difference was highly statistically significant (p=0.012). Conclusion In this present cross-sectional study, we found a 100% prevalence of Candida albicans in the saliva of the study children. There was a highly significant increase in Candida albicans count in SECC children compared to the caries free children. PMID:27656551

  20. Effects of histatin 5 and derived peptides on Candida albicans.

    PubMed Central

    Ruissen, A L; Groenink, J; Helmerhorst, E J; Walgreen-Weterings, E; Van't Hof, W; Veerman, E C; Nieuw Amerongen, A V

    2001-01-01

    Three anti-microbial peptides were compared with respect to their killing activity against Candida albicans and their ability to disturb its cellular and internal membranes. Histatin 5 is an anti-fungal peptide occurring naturally in human saliva, while dhvar4 and dhvar5 are variants of its active domain, with increased anti-microbial activity. dhvar4 has increased amphipathicity compared with histatin 5, whereas dhvar5 has amphipathicity comparable with that of histatin 5. All three peptides caused depolarization of the cytoplasmic and/or mitochondrial membrane, indicating membranolytic activity. For the variant peptides both depolarization and killing occurred at a faster rate. With FITC-labelled peptides, no association with the cytoplasmic membrane was observed, contradicting the formation of permanent transmembrane multimeric peptide pores. Instead, the peptides were internalized and act on internal membranes, as demonstrated with mitochondrion- and vacuole-specific markers. In comparison with histatin 5, the variant peptides showed a more destructive effect on mitochondria. Entry of the peptides and subsequent killing were dependent on the metabolic state of the cells. Blocking of the mitochondrial activity led to complete protection against histatin 5 activity, whereas that of dhvar4 was hardly affected and that of dhvar5 was affected only intermediately. PMID:11368762

  1. Integrating Candida albicans metabolism with biofilm heterogeneity by transcriptome mapping

    PubMed Central

    Rajendran, Ranjith; May, Ali; Sherry, Leighann; Kean, Ryan; Williams, Craig; Jones, Brian L.; Burgess, Karl V.; Heringa, Jaap; Abeln, Sanne; Brandt, Bernd W.; Munro, Carol A.; Ramage, Gordon

    2016-01-01

    Candida albicans biofilm formation is an important virulence factor in the pathogenesis of disease, a characteristic which has been shown to be heterogeneous in clinical isolates. Using an unbiased computational approach we investigated the central metabolic pathways driving biofilm heterogeneity. Transcripts from high (HBF) and low (LBF) biofilm forming isolates were analysed by RNA sequencing, with 6312 genes identified to be expressed in these two phenotypes. With a dedicated computational approach we identified and validated a significantly differentially expressed subnetwork of genes associated with these biofilm phenotypes. Our analysis revealed amino acid metabolism, such as arginine, proline, aspartate and glutamate metabolism, were predominantly upregulated in the HBF phenotype. On the contrary, purine, starch and sucrose metabolism was generally upregulated in the LBF phenotype. The aspartate aminotransferase gene AAT1 was found to be a common member of these amino acid pathways and significantly upregulated in the HBF phenotype. Pharmacological inhibition of AAT1 enzyme activity significantly reduced biofilm formation in a dose-dependent manner. Collectively, these findings provide evidence that biofilm phenotype is associated with differential regulation of metabolic pathways. Understanding and targeting such pathways, such as amino acid metabolism, is potentially useful for developing diagnostics and new antifungals to treat biofilm-based infections. PMID:27765942

  2. Prosthetic joint infections with osteomyelitis due to Candida albicans.

    PubMed

    Lerch, K; Kalteis, T; Schubert, T; Lehn, N; Grifka, J

    2003-12-01

    We report the case of a 78-year-old woman who suffered from a severe soft tissue and bone infection of her left knee 3 years after a total knee-joint replacement without loosening of her endoprosthesis. Cultures from joint aspiration and tissue specimen identified Staphylococcus aureus and Candida albicans. Direct microscopic examination of vital spongy bone and fibrous tissue revealed microabscesses and seeds of yeasts inside the fatty marrow and interface. After removal of the prosthesis several soft tissue and bone specimens were taken during planned re-operations. The histological examination showed no morphological changing, no reduction or extinction of the yeast cells under fluconazole therapy with a dosage of 6 mg kg(-1) body weight (400 mg daily). Curing of the fungal infection with eradication of the yeasts in the bony specimens was achieved with higher doses of 12 mg kg(-1) body weight (800 mg day(-1)) over a 2 month regimen in combination with repeated surgical debridements.

  3. Molecular mechanisms of primary resistance to flucytosine in Candida albicans.

    PubMed

    Hope, William W; Tabernero, Lydia; Denning, David W; Anderson, Michael J

    2004-11-01

    Primary resistance in Candida albicans to flucytosine (5-FC) was investigated in 25 strains by identifying and sequencing the genes FCA1, FUR1, FCY21, and FCY22, which code for cytosine deaminase, uracil phosphoribosyltransferase (UPRT), and two purine-cytosine permeases, respectively. These proteins are involved in pyrimidine salvage and 5-FC metabolism. An association between a polymorphic nucleotide and resistance to 5-FC was found within FUR1 where the substitution of cytidylate for thymidylate at nucleotide position 301 results in the replacement of arginine with cysteine at amino acid position 101 in UPRT. Isolates that are homozygous for this mutation display increased levels of resistance to 5-FC, whereas heterozygous isolates have reduced susceptibility. Three-dimensional protein modeling of UPRT suggests that the Arg101Cys mutation disturbs the quaternary structure of the enzyme, which is postulated to compromise optimal enzyme activity. A single resistant isolate, lacking the above polymorphism in FUR1, has a homozygous polymorphism in FCA1 that results in a glycine-to-aspartate substitution at position 28 in cytosine deaminase.

  4. Oral administration of the broad-spectrum antibiofilm compound toremifene inhibits Candida albicans and Staphylococcus aureus biofilm formation in vivo.

    PubMed

    De Cremer, Kaat; Delattin, Nicolas; De Brucker, Katrijn; Peeters, Annelies; Kucharíková, Soña; Gerits, Evelien; Verstraeten, Natalie; Michiels, Jan; Van Dijck, Patrick; Cammue, Bruno P A; Thevissen, Karin

    2014-12-01

    We here report on the in vitro activity of toremifene to inhibit biofilm formation of different fungal and bacterial pathogens, including Candida albicans, Candida glabrata, Candida dubliniensis, Candida krusei, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis. We validated the in vivo efficacy of orally administered toremifene against C. albicans and S. aureus biofilm formation in a rat subcutaneous catheter model. Combined, our results demonstrate the potential of toremifene as a broad-spectrum oral antibiofilm compound. PMID:25288093

  5. The role of pattern recognition receptors in the innate recognition of Candida albicans.

    PubMed

    Zheng, Nan-Xin; Wang, Yan; Hu, Dan-Dan; Yan, Lan; Jiang, Yuan-Ying

    2015-01-01

    Candida albicans is both a commensal microorganism in healthy individuals and a major fungal pathogen causing high mortality in immunocompromised patients. Yeast-hypha morphological transition is a well known virulence trait of C. albicans. Host innate immunity to C. albicans critically requires pattern recognition receptors (PRRs). In this review, we summarize the PRRs involved in the recognition of C. albicans in epithelial cells, endothelial cells, and phagocytic cells separately. We figure out the differential recognition of yeasts and hyphae, the findings on PRR-deficient mice, and the discoveries on human PRR-related single nucleotide polymorphisms (SNPs).

  6. Antifungal susceptibility and molecular typing of 115 Candida albicans isolates obtained from vulvovaginal candidiasis patients in 3 Shanghai maternity hospitals.

    PubMed

    Ying, Chunmei; Zhang, Hongju; Tang, Zhenhua; Chen, Huifen; Gao, Jing; Yue, Chaoyan

    2016-05-01

    In our multicenter study, we studied the distribution of Candida species in vulvovaginal candidiasis patients and investigated antifungal susceptibility profile and genotype of Candida albicans in vaginal swab. A total of 115 Candida albicans strains were detected in 135 clinical isolates. Minimum inhibitory concentration determinations showed that 83% and 81% of the 115 Candida albicans strains were susceptible to fluconazole and voriconazole. Randomly amplified polymorphic DNA analysis (RAPD) was applied to identify clonally related isolates from different patients at the local level. All tested strains were classified into genotype A (77.4%), genotype B (18.3%), and genotype C (4.3%). Genotype A was further classified into five subtypes and genotype B into two subtypes.Candida albicans was the dominant pathogen of vulvovaginal candidiasis, the majority belonging to genotype A in this study. Exposure to azoles is a risk factor for the emergence of azole resistance among Candida albicans isolated from VVC patients.

  7. Molecular and Histological Association Between Candida albicans from Oral Soft Tissue and Carious Dentine of HIV-Positive Children.

    PubMed

    Blignaut, Elaine; van Heerden, Willie F P

    2015-10-01

    Candida albicans and caries are frequently investigated among healthy and immunosuppressed individuals. The objective of this study was to demonstrate the presence of C. albicans on both oral soft and hard tissue and to investigate, at molecular level, the genetic subtype of the organism from the two oral sites. Tongue swabs and dentine scrapings from 362 HIV-positive children, referred for the extraction of carious primary teeth, were cultured on CHROMagar and identified to species level with ID32C. Histological staining of extracted carious teeth was also done. In patients with positive C. albicans cultures from both the tongue and carious dentine, DNA fingerprinting of such paired isolates was performed, using Southern blot hybridisation with the Ca3 probe. Yeasts were cultured from the tongue of 151 (41.7 %) individuals and 57 (37.7 %) simultaneously yielded positive C. albicans cultures from carious dentine. Nine different yeast spp. were identified from the tongue using the ID32C commercial system, but C. albicans was the only species recovered from carious dentine and histological investigation demonstrated fungal elements penetrated into the dentine and not limited to superficial debris on the floor of the cavity. Twelve of 13 paired isolates of C. albicans revealed identical fingerprinting patterns. The findings from this study demonstrated that in a particular individual, the same genetic subtype of C. albicans was capable of colonising both oral soft tissue and carious dentine. This renders carious teeth a constant source, or reservoir, of potentially infectious agents and, particularly among immunosuppressed individuals, should therefore not be left unattended.

  8. Molecular and Histological Association Between Candida albicans from Oral Soft Tissue and Carious Dentine of HIV-Positive Children.

    PubMed

    Blignaut, Elaine; van Heerden, Willie F P

    2015-10-01

    Candida albicans and caries are frequently investigated among healthy and immunosuppressed individuals. The objective of this study was to demonstrate the presence of C. albicans on both oral soft and hard tissue and to investigate, at molecular level, the genetic subtype of the organism from the two oral sites. Tongue swabs and dentine scrapings from 362 HIV-positive children, referred for the extraction of carious primary teeth, were cultured on CHROMagar and identified to species level with ID32C. Histological staining of extracted carious teeth was also done. In patients with positive C. albicans cultures from both the tongue and carious dentine, DNA fingerprinting of such paired isolates was performed, using Southern blot hybridisation with the Ca3 probe. Yeasts were cultured from the tongue of 151 (41.7 %) individuals and 57 (37.7 %) simultaneously yielded positive C. albicans cultures from carious dentine. Nine different yeast spp. were identified from the tongue using the ID32C commercial system, but C. albicans was the only species recovered from carious dentine and histological investigation demonstrated fungal elements penetrated into the dentine and not limited to superficial debris on the floor of the cavity. Twelve of 13 paired isolates of C. albicans revealed identical fingerprinting patterns. The findings from this study demonstrated that in a particular individual, the same genetic subtype of C. albicans was capable of colonising both oral soft tissue and carious dentine. This renders carious teeth a constant source, or reservoir, of potentially infectious agents and, particularly among immunosuppressed individuals, should therefore not be left unattended. PMID:26153022

  9. A novel antifungal is active against Candida albicans biofilms and inhibits mutagenic acetaldehyde production in vitro.

    PubMed

    Nieminen, Mikko T; Novak-Frazer, Lily; Rautemaa, Vilma; Rajendran, Ranjith; Sorsa, Timo; Ramage, Gordon; Bowyer, Paul; Rautemaa, Riina

    2014-01-01

    The ability of C. albicans to form biofilms is a major virulence factor and a challenge for management. This is evident in biofilm-associated chronic oral-oesophageal candidosis, which has been shown to be potentially carcinogenic in vivo. We have previously shown that most Candida spp. can produce significant levels of mutagenic acetaldehyde (ACH). ACH is also an important mediator of candidal biofilm formation. We have also reported that D,L-2-hydroxyisocaproic acid (HICA) significantly inhibits planktonic growth of C. albicans. The aim of the present study was to investigate the effect of HICA on C. albicans biofilm formation and ACH production in vitro. Inhibition of biofilm formation by HICA, analogous control compounds or caspofungin was measured using XTT to measure biofilm metabolic activity and PicoGreen as a marker of biomass. Biofilms were visualised by scanning electron microscopy (SEM). ACH levels were measured by gas chromatography. Transcriptional changes in the genes involved in ACH metabolism were measured using RT-qPCR. The mean metabolic activity and biomass of all pre-grown (4, 24, 48 h) biofilms were significantly reduced after exposure to HICA (p<0.05) with the largest reductions seen at acidic pH. Caspofungin was mainly active against biofilms pre-grown for 4 h at neutral pH. Mutagenic levels (>40 µM) of ACH were detected in 24 and 48 h biofilms at both pHs. Interestingly, no ACH production was detected from D-glucose in the presence of HICA at acidic pH (p<0.05). Expression of genes responsible for ACH catabolism was up-regulated by HICA but down-regulated by caspofungin. SEM showed aberrant hyphae and collapsed hyphal structures during incubation with HICA at acidic pH. We conclude that HICA has potential as an antifungal agent with ability to inhibit C. albicans cell growth and biofilm formation. HICA also significantly reduces the mutagenic potential of C. albicans biofilms, which may be important when treating bacterial-fungal biofilm

  10. Silicone colonization by non-Candida albicans Candida species in the presence of urine.

    PubMed

    Silva, Sónia; Negri, Melyssa; Henriques, Mariana; Oliveira, Rosário; Williams, David; Azeredo, Joana

    2010-07-01

    Urinary tract infections (UTIs) are the most common nosocomial infections and 80 % are related to the use of urinary catheters. Furthermore, Candida species are responsible for around 15 % of UTIs and an increasing involvement of non-Candida albicans Candida (NCAC) species (e.g. Candida glabrata, Candida tropicalis and Candida parapsilosis) has been recognized. Given the fact that silicone is frequently used in the manufacture of urinary catheters, the aim of this work was to compare both the adhesion and biofilm formation on silicone of different urinary clinical isolates of NCAC species (i.e. C. glabrata, C. tropicalis and C. parapsilosis) in the presence of urine. Several clinical isolates of NCAC species recovered from patients with UTIs, together with reference strains of each species, were examined. Adhesion and biofilm formation were performed in artificial urine and the biofilm biomass was assessed by crystal violet staining. Hydrophobicity and surface charge of cells was determined by measuring contact angles and zeta potential, respectively. The number of viable cells in biofilms was determined by enumeration of c.f.u. after appropriate culture. The biofilm structure was also examined by confocal laser scanning microscopy (CLSM). The results showed that all isolates adhered to silicone in a species- and strain-dependent manner with C. parapsilosis showing the lowest and C. glabrata the highest levels of adhesion. However, these differences in adhesion abilities cannot be correlated with surface properties since all strains examined were hydrophilic and exhibited a similar zeta potential. Despite a higher number of cultivable cells being recovered after 72 h of incubation, stronger biofilm formation was not observed and CLSM showed an absence of extracellular polymeric material for all isolates examined. In summary, this work demonstrated that all tested NCAC species were able to adhere to and survive on silicone in the presence of urine. Furthermore, C

  11. Candida albicans Is Phagocytosed, Killed, and Processed for Antigen Presentation by Human Dendritic Cells

    PubMed Central

    Newman, Simon L.; Holly, Angela

    2001-01-01

    Candida albicans is a component of the normal flora of the alimentary tract and also is found on the mucocutaneous membranes of the healthy host. Candida is the leading cause of invasive fungal disease in premature infants, diabetics, and surgical patients, and of oropharyngeal disease in AIDS patients. As the induction of cell-mediated immunity to Candida is of critical importance in host defense, we sought to determine whether human dendritic cells (DC) could phagocytose and degrade Candida and subsequently present Candida antigens to T cells. Immature DC obtained by culture of human monocytes in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4 phagocytosed unopsonized Candida in a time-dependent manner, and phagocytosis was not enhanced by opsonization of Candida in serum. Like macrophages (Mφ), DC recognized Candida by the mannose-fucose receptor. Upon ingestion, DC killed Candida as efficiently as human Mφ, and fungicidal activity was not enhanced by the presence of fresh serum. Although phagocytosis of Candida by DC stimulated the production of superoxide anion, inhibitors of the respiratory burst (or NO production) did not inhibit killing of Candida, even when phagocytosis was blocked by preincubation of DC with cytochalasin D. Further, although apparently only modest phagolysosomal fusion occurred upon DC phagocytosis of Candida, killing of Candida under anaerobic conditions was almost equivalent to killing under aerobic conditions. Finally, DC stimulated Candida-specific lymphocyte proliferation in a concentration-dependent manner after phagocytosis of both viable and heat-killed Candida cells. These data suggest that, in vivo, such interactions between DC and C. albicans may facilitate the induction of cell-mediated immunity. PMID:11598054

  12. Enhancement of non-Candida antibody responses by Candida albicans cell wall glycoprotein.

    PubMed

    Domer, J E; Elkins, K L; Ennist, D L; Stashak, P W; Garner, R E; Baker, P J

    1987-11-01

    Two cell wall glycoprotein extracts from Candida albicans (glycoprotein [GP] and peptidoglucomannan [PGM]) were tested for their influence on antibody responses to type III pneumococcal polysaccharide and sheep erythrocytes. GP was isolated from lipid-extracted cell walls with ethylenediamine, whereas PGM was extracted with dilute sodium hydroxide. Both glycoproteins increased the number of antibody-producing plaque-forming cells in the spleens of mice immunized with type III polysaccharide or sheep erythrocytes, although PGM appeared to be about 10 times more effective. PGM could be administered up to 3 days prior to immunization with sheep erythrocytes to elicit enhancement; it did not have to be administered by the same route as the immunogen to cause significant enhancement. Enhancement did not appear to be the result of a direct mitogenic effect of GP and PGM on lymphocytes, nor did these glycoproteins appear to stimulate the production of B-cell growth factors or interleukin 2.

  13. Person-to-person transfer of Candida albicans in the spacecraft environment

    NASA Technical Reports Server (NTRS)

    Pierson, D. L.; Mehta, S. K.; Magee, B. B.; Mishra, S. K.

    1995-01-01

    We assessed the exchange of Candida albicans among crew members during 10 Space Shuttle missions. Throat, nasal, urine and faecal specimens were collected from 61 crew members twice before and once after space flights ranging from 7 to 10 days in duration; crews consisted of groups of five, six or seven men and women. Candida albicans was isolated at least once from 20 of the 61 subjects (33%). Candida strains were identified by restriction-fragment length polymorphism (RFLP) after digestion by the endonucleases EcoRI and HinfI; further discrimination was gained by Southern blot hybridization with the C. albicans repeat fragment 27A. Eighteen of the 20 Candida-positive crew members carried different strains of C. albicans in the specimens collected. Possible transfer of C. albicans between members of the same crew was demonstrated only once in the 10 missions studied. We conclude that the transfer of C. albicans among crew members during Space Shuttle flights is less frequent than had been predicted from earlier reports.

  14. Improved gene ontology annotation for biofilm formation, filamentous growth, and phenotypic switching in Candida albicans.

    PubMed

    Inglis, Diane O; Skrzypek, Marek S; Arnaud, Martha B; Binkley, Jonathan; Shah, Prachi; Wymore, Farrell; Sherlock, Gavin

    2013-01-01

    The opportunistic fungal pathogen Candida albicans is a significant medical threat, especially for immunocompromised patients. Experimental research has focused on specific areas of C. albicans biology, with the goal of understanding the multiple factors that contribute to its pathogenic potential. Some of these factors include cell adhesion, invasive or filamentous growth, and the formation of drug-resistant biofilms. The Gene Ontology (GO) (www.geneontology.org) is a standardized vocabulary that the Candida Genome Database (CGD) (www.candidagenome.org) and other groups use to describe the functions of gene products. To improve the breadth and accuracy of pathogenicity-related gene product descriptions and to facilitate the description of as yet uncharacterized but potentially pathogenicity-related genes in Candida species, CGD undertook a three-part project: first, the addition of terms to the biological process branch of the GO to improve the description of fungus-related processes; second, manual recuration of gene product annotations in CGD to use the improved GO vocabulary; and third, computational ortholog-based transfer of GO annotations from experimentally characterized gene products, using these new terms, to uncharacterized orthologs in other Candida species. Through genome annotation and analysis, we identified candidate pathogenicity genes in seven non-C. albicans Candida species and in one additional C. albicans strain, WO-1. We also defined a set of C. albicans genes at the intersection of biofilm formation, filamentous growth, pathogenesis, and phenotypic switching of this opportunistic fungal pathogen, which provides a compelling list of candidates for further experimentation.

  15. Intra-amniotic Candida albicans infection induces mucosal injury and inflammation in the ovine fetal intestine

    PubMed Central

    Nikiforou, Maria; Jacobs, Esmee M.R.; Kemp, Matthew W.; Hornef, Mathias W.; Payne, Matthew S.; Saito, Masatoshi; Newnham, John P.; Janssen, Leon E.W.; Jobe, Alan H.; Kallapur, Suhas G.; Kramer, Boris W.; Wolfs, Tim G.A.M.

    2016-01-01

    Chorioamnionitis is caused by intrauterine infection with microorganisms including Candida albicans (C.albicans). Chorioamnionitis is associated with postnatal intestinal pathologies including necrotizing enterocolitis. The underlying mechanisms by which intra-amniotic C.albicans infection adversely affects the fetal gut remain unknown. Therefore, we assessed whether intra-amniotic C.albicans infection would cause intestinal inflammation and mucosal injury in an ovine model. Additionally, we tested whether treatment with the fungistatic fluconazole ameliorated the adverse intestinal outcome of intra-amniotic C.albicans infection. Pregnant sheep received intra-amniotic injections with 107 colony-forming units C.albicans or saline at 3 or 5 days before preterm delivery at 122 days of gestation. Fetuses were given intra-amniotic and intra-peritoneal fluconazole treatments 2 days after intra-amniotic administration of C.albicans. Intra-amniotic C.albicans caused intestinal colonization and invasive growth within the fetal gut with mucosal injury and intestinal inflammation, characterized by increased CD3+ lymphocytes, MPO+ cells and elevated TNF-α and IL-17 mRNA levels. Fluconazole treatment in utero decreased intestinal C.albicans colonization, mucosal injury but failed to attenuate intestinal inflammation. Intra-amniotic C.albicans caused intestinal infection, injury and inflammation. Fluconazole treatment decreased mucosal injury but failed to ameliorate C.albicans-mediated mucosal inflammation emphasizing the need to optimize the applied antifungal therapeutic strategy. PMID:27411776

  16. Chronic Candida albicans Meningitis in a 4-Year-Old Girl with a Homozygous Mutation in the CARD9 Gene (Q295X).

    PubMed

    Herbst, Martin; Gazendam, Roel; Reimnitz, Denise; Sawalle-Belohradsky, Julie; Groll, Andreas; Schlegel, Paul-Gerhardt; Belohradsky, Bernd; Renner, Ellen; Klepper, Jörg; Grimbacher, Bodo; Kuijpers, Taco; Liese, Johannes

    2015-09-01

    A 4-year-old Turkish girl of consanguineous parents was hospitalized for the evaluation of headaches and recurrent febrile episodes of unknown origin. Her medical history was unremarkable except for a few episodes of uncomplicated oral thrush. Meningitis was diagnosed, and Candida albicans was the only pathogen identified by polymerase chain reaction and culture. Despite systemic antifungal multidrug therapy, a prolonged course of 16 months of therapy was necessary to clear C. albicans from the cerebrospinal fluid. Molecular genetic analysis revealed a homozygous caspase recruitment domain 9 (CARD9) mutation (Q295X), which was reported to predispose to chronic mucocutaneous candidiasis. Immunologic workup excluded predisposing B-cell and T-cell defects. In addition, T cells producing interleukin-17 were repeatedly measured within the normal range. Analyses of neutrophils demonstrated normal nicotinamide adenine dinucleotide phosphate oxidase activity in response to various stimuli including Staphylococcus aureus and C. albicans. Additional neutrophilic functional testing, however, showed a decreased cytotoxicity to nonopsonized C. albicans, indicating an impaired killing mechanism against Candida spp. independent from the production of reactive oxygen species by the nicotinamide adenine dinucleotide phosphate oxidase system. Because this defect was only demonstrated in the absence of opsonins, it might especially predispose to chronic C. albicans infections in the central nervous system where opsonin concentrations are usually low. We, therefore, suggest that due to an additional neutrophil dependent defect CARD9 deficiency predisposes not only to chronic mucocutaneous candidiasis, but also to invasive chronic Candida infections, especially of the central nervous system.

  17. Cilofungin (LY121019), an antifungal agent with specific activity against Candida albicans and Candida tropicalis.

    PubMed Central

    Hall, G S; Myles, C; Pratt, K J; Washington, J A

    1988-01-01

    Cilofungin (LY121019) is an antifungal agent that interferes with beta-glucan synthesis in the cells walls of fungi. The activity of this agent against 256 clinical isolates of yeasts was determined. It was found to be very active in vitro against Candida albicans (MIC for 90% of isolates [MIC90], less than or equal to 0.31 microgram/ml; minimal fungicidal concentration for 90% of isolates [MFC90], less than or equal to 0.31 micrograms/ml) and C. tropicalis (MIC90, less than or equal to 0.31 microgram/ml; MFC90, less than or equal to 0.31 microgram/ml) and moderately active against Torulopsis glabrata (MIC90 and MFC90, less than or equal to 20 micrograms/ml). All C. parapsilosis, Cryptococcus, and Saccharomyces cerevisiae strains were resistant. The activity of cilofungin was affected by medium and inoculum size. Antibiotic medium no. 3 was used as the standard medium. Isolates of C. albicans and C. tropicalis demonstrated a paradoxical effect in Sabouraud dextrose broth and yeast nitrogen base broth in that growth was partially inhibited at MICs equivalent to those in antibiotic medium no. 3, but growth continued, in many instances, throughout all concentrations tested. There was decreased activity of cilofungin with inocula greater than 10(5) CFU/ml. The temperature and duration of incubation did not affect its activity. Images PMID:3058017

  18. New aniline blue dye medium for rapid identification and isolation of Candida albicans.

    PubMed Central

    Goldschmidt, M C; Fung, D Y; Grant, R; White, J; Brown, T

    1991-01-01

    Organic dyes have long been used in diagnostic microbiology to differentiate species by color reactions. We studied the ability of a new noninhibitory medium, YM agar containing 0.01% aniline blue WS dye, Colour Index 42780 (YMAB), to identify Candida albicans among 1,554 yeast specimens obtained from seven clinical laboratories. Appropriate American Type Culture Collection and other characterized strains served as controls. A total of 487 of the clinical strains were identified as C. albicans. The remainder were other Candida species and non-Candida yeasts. Clinical isolates and controls were grown on Sabouraud agar for 18 h at 30 degrees C and then transferred to YMAB. Plates were incubated for 12 to 18 h at 30 degrees C, and colonies were observed for yellow-green fluorescence under long-wave UV light (A365). All control strains of C. albicans and Candida stellatoidea fluoresced, as did 480 of the 490 isolates designated as C. albicans (which included 3 strains of C. stellatoidea). Cells of C. albicans grown on YMAB produced germ tubes in serum. Only five of the other 1,062 non-C. albicans yeasts fluoresced. The sensitivity and specificity were 98.0 and 99.5%, respectively, with a predictive value of 99.1%. A fluorescent metabolite was found in cell wall particulate fractions of C. albicans sonic extracts grown on YMAB but not in non-C. albicans yeasts. This metabolite showed the same spectral curve as those of metabolites from whole cells in a recording spectrofluorometer when it was excited at 400 nm and scanned from 420 to 550 nm. Thus, growth on YMAB generates the production of a fluorescent moiety that can be used to specifically identify C. albicans within 12 to 18 h. Images PMID:1864924

  19. [A case report of pulmonary infiltration with eosinophilia syndrome induced by Candida albicans].

    PubMed

    Miyagawa, H; Yokota, S; Kajimoto, K; Makimoto, K; Sato, K; Nabe, M; Tada, S; Kimura, I

    1992-01-01

    A sixty six-year-old female who had been treated for bronchial asthma for about 25 years was admitted to the hospital with complaints of episodes of dyspnea, eosinophilia and infiltrative shadows in the chest X-ray film. An infiltrative shadow appeared to move from the left to the right lung field and finally formed a shadow of atelectasis in the middle field of the right lung. A sputum culture showed only Candida albicans. Allergic and immunologic examination revealed high IgE serum levels with specific IgE against Candida albicans in high titer, and Aspergillus fumigatus in low titer. The precipitating antibody was shown only against Candida antigen. Additionally, the blastogenic response to Candida antigen was high in comparison with other fungal antigens including Aspergillus fumigatus. The clinical features and laboratory findings of this patient were found to satisfy Rosenberg's criteria for allergic bronchopulmonary aspergillosis (ABPA), except for the existence of Candida albicans in place of Aspergillus species as the causative antigen. The pathogenesis of PIE syndrome has been studied and various allergic mechanisms against many antigens reported. In this patient Candida albicans could be playing the crucial role in the formation of PIE syndrome, which might be best described as allergic bronchopulmonary candidiasis (ABPC). PMID:1554325

  20. Imaging morphogenesis of Candida albicans during infection in a live animal

    NASA Astrophysics Data System (ADS)

    Mitra, Soumya; Dolan, Kristy; Foster, Thomas H.; Wellington, Melanie

    2010-01-01

    Candida albicans is an opportunistic human fungal pathogen that requires an intact host immune response to prevent disease. Thus, studying host-pathogen interactions is critical to understanding and preventing this disease. We report a new model infection system in which ongoing C. albicans infections can be imaged at high spatial resolution in the ears of living mice. Intradermal inoculation into mouse ears with a C. albicans strain expressing green fluorescent protein results in systemic C. albicans infection that can be imaged in vivo using confocal microscopy. We observed filamentous growth of the organism in vivo as well as formation of microabscesses. This model system will allow us to gain significant new information about C. albicans pathogenesis through studies of host-C. albicans interactions in the native environment.

  1. Imaging morphogenesis of Candida albicans during infection in a live animal.

    PubMed

    Mitra, Soumya; Dolan, Kristy; Foster, Thomas H; Wellington, Melanie

    2010-01-01

    Candida albicans is an opportunistic human fungal pathogen that requires an intact host immune response to prevent disease. Thus, studying host-pathogen interactions is critical to understanding and preventing this disease. We report a new model infection system in which ongoing C. albicans infections can be imaged at high spatial resolution in the ears of living mice. Intradermal inoculation into mouse ears with a C. albicans strain expressing green fluorescent protein results in systemic C. albicans infection that can be imaged in vivo using confocal microscopy. We observed filamentous growth of the organism in vivo as well as formation of microabscesses. This model system will allow us to gain significant new information about C. albicans pathogenesis through studies of host-C. albicans interactions in the native environment.

  2. An Optimized Lock Solution Containing Micafungin, Ethanol and Doxycycline Inhibits Candida albicans and Mixed C. albicans – Staphyloccoccus aureus Biofilms

    PubMed Central

    Lown, Livia; Peters, Brian M.; Walraven, Carla J.; Noverr, Mairi C.; Lee, Samuel A.

    2016-01-01

    Candida albicans is a major cause of catheter-related bloodstream infections and is associated with high morbidity and mortality. Due to the propensity of C. albicans to form drug-resistant biofilms, the current standard of care includes catheter removal; however, reinsertion may be technically challenging or risky. Prolonged exposure of an antifungal lock solution within the catheter in conjunction with systemic therapy has been experimentally attempted for catheter salvage. Previously, we demonstrated excellent in vitro activity of micafungin, ethanol, and high-dose doxycycline as single agents for prevention and treatment of C. albicans biofilms. Thus, we sought to investigate optimal combinations of micafungin, ethanol, and/or doxycycline as a lock solution. We performed two- and three-drug checkerboard assays to determine the in vitro activity of pairwise or three agents in combination for prevention or treatment of C. albicans biofilms. Optimal lock solutions were tested for activity against C. albicans clinical isolates, reference strains and polymicrobial C. albicans-S. aureus biofilms. A solution containing 20% (v/v) ethanol, 0.01565 μg/mL micafungin, and 800 μg/mL doxycycline demonstrated a reduction of 98% metabolic activity and no fungal regrowth when used to prevent fungal biofilm formation; however there was no advantage over 20% ethanol alone. This solution was also successful in inhibiting the regrowth of C. albicans from mature polymicrobial biofilms, although it was not fully bactericidal. Solutions containing 5% ethanol with low concentrations of micafungin and doxycycline demonstrated synergistic activity when used to prevent monomicrobial C. albicans biofilm formation. A combined solution of micafungin, ethanol and doxycycline is highly effective for the prevention of C. albicans biofilm formation but did not demonstrate an advantage over 20% ethanol alone in these studies. PMID:27428310

  3. An Optimized Lock Solution Containing Micafungin, Ethanol and Doxycycline Inhibits Candida albicans and Mixed C. albicans - Staphyloccoccus aureus Biofilms.

    PubMed

    Lown, Livia; Peters, Brian M; Walraven, Carla J; Noverr, Mairi C; Lee, Samuel A

    2016-01-01

    Candida albicans is a major cause of catheter-related bloodstream infections and is associated with high morbidity and mortality. Due to the propensity of C. albicans to form drug-resistant biofilms, the current standard of care includes catheter removal; however, reinsertion may be technically challenging or risky. Prolonged exposure of an antifungal lock solution within the catheter in conjunction with systemic therapy has been experimentally attempted for catheter salvage. Previously, we demonstrated excellent in vitro activity of micafungin, ethanol, and high-dose doxycycline as single agents for prevention and treatment of C. albicans biofilms. Thus, we sought to investigate optimal combinations of micafungin, ethanol, and/or doxycycline as a lock solution. We performed two- and three-drug checkerboard assays to determine the in vitro activity of pairwise or three agents in combination for prevention or treatment of C. albicans biofilms. Optimal lock solutions were tested for activity against C. albicans clinical isolates, reference strains and polymicrobial C. albicans-S. aureus biofilms. A solution containing 20% (v/v) ethanol, 0.01565 μg/mL micafungin, and 800 μg/mL doxycycline demonstrated a reduction of 98% metabolic activity and no fungal regrowth when used to prevent fungal biofilm formation; however there was no advantage over 20% ethanol alone. This solution was also successful in inhibiting the regrowth of C. albicans from mature polymicrobial biofilms, although it was not fully bactericidal. Solutions containing 5% ethanol with low concentrations of micafungin and doxycycline demonstrated synergistic activity when used to prevent monomicrobial C. albicans biofilm formation. A combined solution of micafungin, ethanol and doxycycline is highly effective for the prevention of C. albicans biofilm formation but did not demonstrate an advantage over 20% ethanol alone in these studies. PMID:27428310

  4. Echinocandin to fluconazole step-down therapy in critically ill patients with invasive, susceptible Candida albicans infections.

    PubMed

    van der Geest, Patrick J; Rijnders, Bart J A; Vonk, Alieke G; Groeneveld, A B Johan

    2016-03-01

    Invasive Candida spp. infections are increasingly diagnosed in critically ill patients. For initial treatment, an echinocandin is recommended with a possible step-down to fluconazole when the patients' condition is improving and the isolate appears susceptible, but there are no data to support such policy. We studied the safety and efficacy of step-down therapy in critically ill patients with culture proven deep seated or bloodstream infections by C. albicans susceptible to fluconazole. All patients admitted into the intensive care unit from January 2010 to December 2014, who had a culture proven invasive C. albicans infection and received initial treatment with an echinocandin for at least 4 days were included. Data on patient characteristics, treatment and vital outcomes were assessed. Of the 56 patients, 32 received step-down fluconazole therapy, at median day 5, whereas the echinocandin was continued in the other 24. No differences where seen in baseline characteristics or risk factors for invasive C. albicans infection between the two groups. Response rates were similar and no difference where seen in 28-day or 90-day mortality between the groups. Step-down therapy to fluconazole may be safe and effective in critically ill patients with invasive infections by C. albicans, susceptible to fluconazole, who have clinically improved as early as 4 days after start of treatment with an echinocandin.

  5. Delicate Metabolic Control and Coordinated Stress Response Critically Determine Antifungal Tolerance of Candida albicans Biofilm Persisters

    PubMed Central

    Li, Peng; Alpi, Emanuele; Vizcaino, Juan A.

    2015-01-01

    Candida infection has emerged as a critical health care burden worldwide, owing to the formation of robust biofilms against common antifungals. Recent evidence shows that multidrug-tolerant persisters critically account for biofilm recalcitrance, but their underlying biological mechanisms are poorly understood. Here, we first investigated the phenotypic characteristics of Candida biofilm persisters under consecutive harsh treatments of amphotericin B. The prolonged treatments effectively killed the majority of the cells of biofilms derived from representative strains of Candida albicans, Candida glabrata, and Candida tropicalis but failed to eradicate a small fraction of persisters. Next, we explored the tolerance mechanisms of the persisters through an investigation of the proteomic profiles of C. albicans biofilm persister fractions by liquid chromatography-tandem mass spectrometry. The C. albicans biofilm persisters displayed a specific proteomic signature, with an array of 205 differentially expressed proteins. The crucial enzymes involved in glycolysis, the tricarboxylic acid cycle, and protein synthesis were markedly downregulated, indicating that major metabolic activities are subdued in the persisters. It is noteworthy that certain metabolic pathways, such as the glyoxylate cycle, were able to be activated with significantly increased levels of isocitrate lyase and malate synthase. Moreover, a number of important proteins responsible for Candida growth, virulence, and the stress response were greatly upregulated. Interestingly, the persisters were tolerant to oxidative stress, despite highly induced intracellular superoxide. The current findings suggest that delicate metabolic control and a coordinated stress response may play a crucial role in mediating the survival and antifungal tolerance of Candida biofilm persisters. PMID:26195524

  6. The problems of urinary tract infections with Candida spp. aetiology in women.

    PubMed

    Tomczak, Hanna; Szałek, Edyta; Grześkowiak, Edmund

    2014-01-01

    Urinary tract infections (UTIs) in women are a growing clinical concern. The most frequent risk factors of UTIs with fungal aetiology in women are: antibiotic therapy (especially broad-spectrum antibiotics), immunosuppressive therapy, diabetes, malnutrition, pregnancy, and frequent intercourse. The aim of the study was to analyse urinary tract infections with Candida spp. aetiology in women hospitalised at the Clinical Hospital in Poznań, Poland, between 2009 and 2011. The investigations revealed that as many as 71% of positive urine cultures with Candida fungi came from women. The following fungi were most frequently isolated from the patients under analysis: C. albicans (47%), C. glabrata (31%), C. tropicalis (6%), C. krusei (3%). In order to diagnose a UTI the diagnosis cannot be based on a single result of a urine culture. Due to the small number of antifungal drugs and high costs of treatment, antifungal drugs should be applied with due consideration and care.

  7. Candida albicans Transcriptional Profiling Within Biliary Fluid From a Patient With Cholangitis, Before and After Antifungal Treatment and Surgical Drainage

    PubMed Central

    Clancy, Cornelius J.; Meslin, Camille; Badrane, Hassan; Cheng, Shaoji; Losada, Liliana C.; Nierman, William C.; Vergidis, Pascalis; Clark, Nathan L.; Nguyen, M. Hong

    2016-01-01

    We used ribonucleic acid sequencing to profile Candida albicans transcription within biliary fluid from a patient with cholangitis; samples were collected before and after treatment with fluconazole and drainage. Candida albicans transcriptomes at the infection site distinguished treated from untreated cholangitis. After treatment, 1131 C. albicans genes were differentially expressed in biliary fluid. Up-regulated genes were enriched in hyphal growth, cell wall organization, adhesion, oxidation reduction, biofilm, and fatty acid and ergosterol biosynthesis. This is the first study to define Candida global gene expression during deep-seated human infection. Successful treatment of cholangitis induced C. albicans genes involved in fluconazole responses and pathogenesis.

  8. Avian pox infection with secondary Candida albicans encephalitis in a juvenile golden eagle (Aquila chrysaetos).

    PubMed

    Shrubsole-Cockwill, Alana N; Millins, Caroline; Jardine, Claire; Kachur, Kelti; Parker, Dennilyn L

    2010-03-01

    Abstract: A juvenile golden eagle (Aquila chrysaetos) was presented with proliferative epithelial lesions, consistent with avian poxvirus infection, around the eyes, on commissures of the beak, and on both feet. Despite treatment, the eagle declined clinically, and, 15 days after presentation, the eagle began seizuring and was euthanatized because of a poor prognosis. On postmortem examination, avian poxvirus infection was confirmed in the nodular skin lesions, and Candida albicans was cultured from the skin, lungs, and brain. Breaks in the skin barrier from poxvirus infection likely led to secondary infection with C albicans. Systemic vascular dissemination of C albicans to the brain resulted in thrombosis, hemorrhage, local hypoxia, and the clinically observed seizures. The combination of the breach in the primary immune system, immunosuppression, and a prolonged course of antibiotics were contributory factors to the opportunistic fungal infection in this eagle. Candida albicans should be considered as a differential diagnosis for encephalitis in an immunocompromised avian patient. PMID:20496607

  9. [In vitro nystatin sensitivity of vaginal isolates of Candida spp].

    PubMed

    Andreu, C M; Medina, Y E; Gonzáles, T C; Llanes, D M

    2001-01-01

    The minimum inhibitory concentration (MIC) of nistatine, one of the most used antifungal agents for this micosis, was determined in 68 Candida strains isolated from vaginal smears. Candida albicans represented 75% of the total strains whereas C. parapsilosis, C. krusei and C. glabrata were much less frequently found. The predisposing factors were pregnancy and antibacterial treatment whereas leukorrhea and itching were the prevailing symptoms in most of the cases. MIC values from the use of a broth dilution method ranged from 0,5-8mg/mL and the geometric mean was 1.36mg/ mL. For C. albicans, MIC was 4mg/mL due to two strains that showed the highest MIC values (8 mg/mL). Similarly, the strains showed low MIC values, this means that therapeutic failures are not inherent to the emergence of resistant strains.

  10. Reduced inhibition of Candida albicans adhesion by saliva from patients receiving oral cancer therapy.

    PubMed Central

    Umazume, M; Ueta, E; Osaki, T

    1995-01-01

    The effect of saliva on the adhesion of Candida albicans to epithelial cells was examined in vitro by using saliva from healthy controls and patients with oral squamous cell carcinoma. The adhesion of C. albicans to established epithelial tumor cells was reduced by 40% by salivary treatment of the C. albicans or epithelial cells. The inhibitory activity of saliva was almost completely abolished by anti-secretory immunoglobulin A antibody, concanavalin A, and mannose. Compared with saliva from healthy individuals, that from patients who had received chemoradiotherapy for oral carcinoma showed reduced suppression of C. albicans adhesion, which accompanied decreased salivary secretory immunoglobulin A and lactoferrin concentrations. A greater number of C. albicans cells adhered to buccal cells obtained from patients who had received chemoradiotherapy than to those from healthy individuals. Treatment of either epithelial cells or C. albicans with anticancer drugs induced an increase in adherence of epithelial cells and yeast cells. In contrast, concanavalin A- and mannose-pretreated C. albicans exhibited reduced adhesion to epithelial cells. No further decrease of C. albicans adhesion was observed when both epithelial cells and yeast phase C. albicans were treated with mannose. In conclusion, the inhibition of C. albicans adhesion by saliva depends largely on mannose residues on salivary glycoproteins and mannose is one of the binding ligands on both C. albicans and epithelial cells. In addition, anticancer therapy may induce oral C. albicans overgrowth by decreasing salivation and the concentrations of glycoproteins in saliva inhibiting C. albicans adhesion and by increasing the adhesive properties of both C. albicans and oral epithelial cells. PMID:7714204

  11. Effects of simulated microgravity by RCCS on the biological features of Candida albicans.

    PubMed

    Jiang, Wenjun; Xu, Bingxin; Yi, Yong; Huang, Yuling; Li, Xiao-Ou; Jiang, Fuquan; Zhou, Jinlian; Zhang, Jianzhong; Cui, Yan

    2014-01-01

    During the spaceflight, a wide variety of microorganisms may be carried to the outer space by astronauts and aviation component. The yeast Candida albicans is an important opportunistic pathogen responsible for a variety of cutaneous and systemic human infections in human body, and the yeast cell itself could be affected by various stressful environmental factors including the weightless environment. We evaluated the effects of simulated microgravity on biological features of Candida albicans using the rotary cell culture system (RCCS). The growth curves of Candida albicans cultured in RCCS were recorded by spectrophotometer, the morphogenic switches were observed by optical microscope, and the viability of cells exposed to the various concentrations of fluconazole solution was assayed by flow cytometry at 7th, 14th and 21st day of experiment. The results showed that Candida albicans SC5314 under modeled microgravity were manifested as the growth curves leftward-shifted, lag phase shortened, along with logarithmic phase and stationary phase forwarded (P < 0.05). The simulated microgravity increased the growth rate and mycelia formation of Candida albicans. A statistically significant decrease in viability was detected in cells cultured for 7 d, 14 d and 21 d in group of simulated microgravity compared with the control group (P < 0.05). The increase of exposure time to simulate microgravity resulted in the decrease of viability of cells accordingly in same drug concentration compared with the control group. The study demonstrated that the three weeks' simulated microgravity in RCCS had a noticeable affect on the growth status of mycelia and spores and the morphogenic switches of Candida albicans, meanwhile, the yeast cells under simulated microgravity showed an increased antifungal susceptibility to fluconazole. PMID:25120754

  12. Candida albicans and non-albicans species as etiological agent of vaginitis in pregnant and non-pregnant women.

    PubMed

    Babic, Mirela; Hukic, Mirsada

    2010-02-01

    Pregnancy represents a risk factor in the occurrence of vaginal candidosis. The objectives of our study were: to make determination of the microscopic findings of vaginal swab, frequency of Candida species in the culture of pregnant women and patients who are not pregnant, determine the Candida species in all cultures, and to determine the frequency and differences in the frequency of C. albicans and other non-albicans species. In one year study performed during 2006 year, we tested patients of Gynaecology and Obstetrics clinic of the Clinical Centre in Sarajevo and Gynaecology department of the General hospital in Sarajevo. 447 woman included in the study were separated in two groups: 203 pregnant (in the last trimester of pregnancy), and 244 non-pregnant woman in period of fertility. Each vaginal swab was examined microscopically. The yeast, number of colonies, and the species of Candida were determined on Sabouraud dextrose agar with presence of antibiotics. For determination of Candida species, we used germ tube test for detection of C. albicans, and cultivation on the selective medium and assimilation tests for detection of non-albicans species. The results indicated positive microscopic findings in the test group (40,9%), as well as greater number of positive cultures (46,8%). The most commonly detected species for both groups was C. albicans ( test group 40.9% and control group 23,0%). The most commonly detected non-albicans species for the test group were C. glabrata (4,2 %) and C. krusei (3,2%), and for the control group were C. glabrata (3,2%) and C. parapsilosis (3,2%). The microscopic findings correlated with the number of colonies in positive cultures. In the test group, we found an increased number of yeasts (64,3%), and the pseudopyphae and blastopores by microscopic examination as an indication of infection. In the control group, we found a small number of yeasts (64,6%) , in the form of blastopores, as an indication of the candida colonisation. Our

  13. Detection of Candida albicans mRNA in Archival Histopathology Samples by Reverse Transcription-PCR

    PubMed Central

    Beggs, Kyle T.; Holmes, Ann R.; Cannon, Richard D.; Rich, Alison M.

    2004-01-01

    The feasibility of detecting Candida albicans mRNA in formalin-fixed paraffin-embedded archival human histopathology specimens by reverse transcription-PCR (RT-PCR) was investigated. RT with gene-specific primers was used to detect five single-copy C. albicans gene transcripts, including those of two housekeeping genes, in oral candidiasis samples up to 8 years of age. PMID:15131211

  14. Effectiveness of Photodynamic Therapy for the Inactivation of Candida spp. on Dentures: In Vitro Study

    PubMed Central

    Mima, Ewerton Garcia de Oliveira; Ribeiro, Daniela Garcia; Dovigo, Livia Nordi; Vergani, Carlos Eduardo; Bagnato, Vanderlei Salvador

    2011-01-01

    Abstract Objective: This in vitro study evaluated the effectiveness of photodynamic therapy (PDT) for the inactivation of different species of Candida on maxillary complete dentures. Background data: The treatment of denture stomatitis requires the inactivation of Candida spp. on dentures. PDT has been reported as an effective method for Candida inactivation. Methods: Reference strains of C. albicans, C. glabrata, C. tropicalis, C. dubliniensis and C. krusei were tested. Thirty-four dentures were fabricated in a standardized procedure and subjected to ethylene oxide sterilization. The dentures were individually inoculated with one of the strains and incubated at 37°C for 24 h. Dentures submitted to PDT (P+L+) were individually sprayed with 50 mg/L of Photogem® (PS) and, after 30 min, illuminated by LED light for 26 min (37.5 J/cm2). Additional dentures were treated only with PS (P+L-) or light (P-L+) or neither (P-L-). Samples of serial dilutions were spread on Sabouraud dextrose agar and incubated at 37°C for 48 h. The colonies were counted and the values of log (cfu/mL) were analyzed by Kruskall-Wallis and Dunn tests (p<0.05). Results: For all species of Candida, PDT resulted in significant reduction (p<0.05) of cfu/mL values from dentures when compared with P-L- (reductions from 1.73 to 3.99 log10). Significant differences (p<0.05), but lower reductions, were also observed for P+L- and P-L+when compared with P-L- for some species of Candida. Conclusions: PDT was an effective method for reducing Candida spp. on dentures. PMID:21916614

  15. The synthesis and synergistic antifungal effects of chalcones against drug resistant Candida albicans.

    PubMed

    Wang, Yuan-Hua; Dong, Huai-Huai; Zhao, Fei; Wang, Jie; Yan, Fang; Jiang, Yuan-Ying; Jin, Yong-Sheng

    2016-07-01

    To identify effective and low toxicity synergistic antifungal compounds, 24 derivatives of chalcone were synthesized to restore the effectiveness of fluconazole against fluconazole-resistant Candida albicans. The minimal inhibitory concentration (MIC80) and the fractional inhibitory concentration index (FICI) of the antifungal synergist fluconazole were measured against fluconazole-resistant Candida albicans. This was done via methods established by the clinical and laboratory standards institute (CLSI). Of the synthesized compounds, 2'-hydroxy-4'-methoxychalcone (8) exhibited the most potent in vitro (FICI=0.007) effects. The structure activity relationship of the compounds are then discussed. PMID:27210436

  16. Betamethasone augments the antifungal effect of menadione--towards a novel anti-Candida albicans combination therapy.

    PubMed

    Jakab, Ágnes; Emri, Tamás; Sipos, Lilla; Kiss, Ágnes; Kovács, Renátó; Dombrádi, Viktor; Kemény-Beke, Ádám; Balla, József; Majoros, László; Pócsi, István

    2015-08-01

    The fluorinated glucocorticoid betamethasone stimulated both the extracellular phospholipase production and hypha formation of the opportunistic human pathogen Candida albicans and also decreased the efficiency of the polyene antimycotics amphotericin B and nystatin against C. albicans in a dose-dependent manner. Importantly, betamethasone increased synergistically the anti-Candida activity of the oxidative stress generating agent menadione, which may be exploited in future combination therapies to prevent or cure C. albicans infections, in the field of dermatology.

  17. Cloning of the RHO1 gene from Candida albicans and its regulation of beta-1,3-glucan synthesis.

    PubMed Central

    Kondoh, O; Tachibana, Y; Ohya, Y; Arisawa, M; Watanabe, T

    1997-01-01

    The Saccharomyces cerevisiae RHO1 gene encodes a low-molecular-weight GTPase. One of its recently identified functions is the regulation of beta-1,3-glucan synthase, which synthesizes the main component of the fungal cell wall (J. Drgonova et al., Science 272:277-279, 1996; T. Mazur and W. Baginsky, J. Biol. Chem. 271:14604-14609, 1996; and H. Qadota et al., Science 272:279-281, 1996). From the opportunistic pathogenic fungus Candida albicans, we cloned the RHO1 gene by the PCR and cross-hybridization methods. Sequence analysis revealed that the Candida RHO1 gene has a 597-nucleotide region which encodes a putative 22.0-kDa peptide. The deduced amino acid sequence predicts that Candida albicans Rho1p is 82.9% identical to Saccharomyces Rho1p and contains all the domains conserved among Rho-type GTPases from other organisms. The Candida albicans RHO1 gene could rescue a S. cerevisiae strain containing a rho1 deletion. Furthermore, recombinant Candida albicans Rho1p could reactivate the beta-1,3-glucan synthesis activities of both C. albicans and S. cerevisiae membranes in which endogenous Rho1p had been depleted by Tergitol NP-40-NaCl treatment. Candida albicans Rho1p was copurified with the beta-1,3-glucan synthase putative catalytic subunit, Candida albicans Gsc1p, by product entrapment. Candida albicans Rho1p was shown to interact directly with Candida albicans Gsc1p in a ligand overlay assay and a cross-linking study. These results indicate that Candida albicans Rho1p acts in the same manner as Saccharomyces cerevisiae Rho1p to regulate beta-1,3-glucan synthesis. PMID:9401032

  18. Candida albicans and C. tropicalis Isolates from the Expired Breathes of Captive Dolphins and Their Environments in an Aquarium.

    PubMed

    Takahashi, Hideo; Ueda, Keiichi; Itano, Eiko Nakagawa; Yanagisawa, Makio; Murata, Yoshiteru; Murata, Michiko; Yaguchi, Takashi; Murakami, Masaru; Kamei, Katsuhiko; Inomata, Tomo; Miyahara, Hirokazu; Sano, Ayako; Uchida, Senzo

    2010-12-22

    Genotypes of Candida spp. isolated from exhalation of 20 dolphins, 11 water samples from captive pools, and 24 oral cavities of staff members in an aquarium using a combination of multiple drug resistance 1 gene (MDR1) and the internal transcribed spacer (ITS) 1 5.8s-ITS 2 regions of ribosomal RNA gene (ITS rDNA) sequences were studied. The holding ratios of the dolphins, captive pools, and staff members were 70, 90, and 29%, respectively. Isolated pathogenic yeast species common to the dolphins and environments were Candida albicans and C. tropicalis. Identical genotypes in both Candida spp. based on the combination of MDR1 and ITSrDNA were found in some dolphins, between a dolphin and a staff, among dolphins and environments, and among environments. The results indicated the diffusion and exchange of pathogenic yeasts at the aquarium among dolphins and environments. The isolates at the aquarium showed higher rates of resistance to azole antifungals compared to reference isolates.

  19. Frequency, pathogenicity and microbiologic outcome of non-Candida albicans candiduria.

    PubMed

    Occhipinti, D J; Gubbins, P O; Schreckenberger, P; Danziger, L H

    1994-06-01

    A retrospective review of urine cultures obtained from patients at the University of Illinois Hospital revealed that the frequency of isolation of non-albicans Candida species increased significantly from 1990 to 1991 (p = 0.0003), while the frequency of isolation of Candida albicans species decreased significantly (p = 0.0006). Patients with urine cultures positive for non-albicans Candida species of Torulopsis glabrata during 1991 were identified for review. Sixty-seven patients were eligible for evaluation. Non-albicans candiduria developed in an average of 12 days. Identical fungal species were isolated from the blood following a positive urine culture in only two patients. Twenty patients were treated; candiduria persisted in 9 (45%), while resolution occurred in 11 (55%). The remaining 47 patients were not treated. Non-albicans candiduria persisted in 30 (64%) of these patients and resolved in 15 (32%); in the remaining two patients (4%) the microbiologic outcome was undetermined. The difference in microbiologic outcomes between treated and untreated patients was not significant using the Chi-square test (p = 0.170). Non-albicans candiduria developed rapidly, frequently persisted whether treated or untreated, and rarely progressed to candidemia.

  20. Systemic Staphylococcus aureus infection mediated by Candida albicans hyphal invasion of mucosal tissue

    PubMed Central

    Schlecht, Lisa Marie; Peters, Brian M.; Krom, Bastiaan P.; Freiberg, Jeffrey A.; Hänsch, Gertrud M.; Filler, Scott G.

    2015-01-01

    Candida albicans and Staphylococcus aureus are often co-isolated in cases of biofilm-associated infections. C. albicans can cause systemic disease through morphological switch from the rounded yeast to the invasive hyphal form. Alternatively, systemic S. aureus infections arise from seeding through breaks in host epithelial layers although many patients have no documented portal of entry. We describe a novel strategy by which S. aureus is able to invade host tissue and disseminate via adherence to the invasive hyphal elements of Candida albicans. In vitro and ex vivo findings demonstrate a specific binding of the staphylococci to the candida hyphal elements. The C. albicans cell wall adhesin Als3p binds to multiple staphylococcal adhesins. Furthermore, Als3p is required for C. albicans to transport S. aureus into the tissue and cause a disseminated infection in an oral co-colonization model. These findings suggest that C. albicans can facilitate the invasion of S. aureus across mucosal barriers, leading to systemic infection in co-colonized patients. PMID:25332378

  1. HWY-289, a novel semi-synthetic protoberberine derivative with multiple target sites in Candida albicans.

    PubMed

    Park, K S; Kang, K C; Kim, K Y; Jeong, P Y; Kim, J H; Adams, D J; Kim, J H; Paik, Y K

    2001-05-01

    The antifungal properties of 515 synthetic and semi-synthetic protoberberines were investigated. HWY-289 was chosen for further study because it exhibited the most significant anti-Candida activity (MICs were 1.56 mg/L for Candida albicans and Candida krusei; 6.25 mg/L for Candida guilliermondii) but did not demonstrate toxicity in rats. HWY-289 inhibited the incorporation of L-[methyl-(14)C]methionine into the C-24 of ergosterol in whole cells of C. albicans (IC(50) 20 microM). However, HWY-289 (100 microM) had no effect on mammalian cholesterol biosynthesis in rat microsomes while miconazole (100 microM) was a potent inhibitor of cholesterol biosynthesis under identical assay conditions. A second major target site for HWY-289 was identified that involves cell wall biosynthesis in C. albicans. HWY-289 was a potent inhibitor of the chitin synthase isozymes CaCHS1 and CaCHS2, with IC(50) values of 22 microM for each enzyme. The effect was highly specific in that HWY-289 had no significant effect on C. albicans CaCHS3 (IC(50) > 200 microM). Thus, HWY-289 compared favourably with well-established antifungal agents as an inhibitor of the growth of Candida species in vitro, and may have considerable potential as a new class of antifungal agent that lacks toxic side effects in the human host.

  2. Comparative adherence of Candida albicans and Candida dubliniensis to human buccal epithelial cells and extracellular matrix proteins.

    PubMed

    Jordan, Rachael P C; Williams, David W; Moran, Gary P; Coleman, David C; Sullivan, Derek J

    2014-04-01

    Candida albicans and Candida dubliniensis are very closely related pathogenic yeast species. Despite their close relationship, C. albicans is a far more successful colonizer and pathogen of humans. The purpose of this study was to determine if the disparity in the virulence of the two species is attributed to differences in their ability to adhere to human buccal epithelial cells (BECs) and/or extracellular matrix proteins. When grown overnight at 30°C in yeast extract peptone dextrose, genotype 1 C. dubliniensis isolates were found to be significantly more adherent to human BECs than C. albicans or C. dubliniensis genotypes 2-4 (P < 0.001). However, when the yeast cells were grown at 37°C, no significant difference between the adhesion of C. dubliniensis genotype 1 and C. albicans to human BECs was observed, and C. dubliniensis genotype 1 and C. albicans adhered to BECs in significantly greater numbers than the other C. dubliniensis genotypes (P < 0.001). Using surface plasmon resonance analysis, C. dubliniensis isolates were found to adhere in significantly greater numbers than C. albicans to type I and IV collagen, fibronectin, laminin, vitronectin, and proline-rich peptides. These data suggest that C. albicans is not more adherent to epithelial cells or matrix proteins than C. dubliniensis and therefore other factors must contribute to the greater levels of virulence exhibited by C. albicans.

  3. Inhibitory Effect of Alpha-Mangostin on Adhesion of Candida albicans to Denture Acrylic

    PubMed Central

    Kaomongkolgit, Ruchadaporn; Jamdee, Kusuma

    2015-01-01

    Objective: Candida-associated denture stomatitis is a very common disease affecting denture wearers. It is characterized by the presence of yeast biofilm on the denture, primarily associated with C. albicans. The investigation of agents that can reduce C. albicans adhesion may represent a significant advancement in the prevention and treatment of this disease. This study aims to investigate the effect of alpha-mangostin on the in vitro adhesion of C. albicans to denture acrylic and germ tube formation by C. albicans and to compare its activity with clotrimazole which is a topical antifungal agent commonly used for the treatment of Candida-associated denture stomatitis. Materials and Methodology: Alpha-mangostin was extracted by thin layer chromatography. The effect of alpha-mangostin on adhesion of C. albicans to denture acrylic was determined by using a colorimetric tetrazolium assay and germ tube formation by C. albicans was determined by using the counting chamber. Results: A significant reduction of C. albicans adhesion to denture acrylic was evident after exposure to 2,000 µg/ml of alpha-mangostin for only 15 min. In addition, the 2,000 µg/ml of the alpha-mangostin-treated C. albicans had a reduced ability for germ tube formation. These inhibitory effects of alpha-mangostin were as effective as clotrimazole. Conclusion: Alpha-mangostin has antifungal property against C. albicans by inhibiting the adhesion to denture acrylic and germ tube formation in vitro. These results suggest the potential application of alpha-mangostin as a topical medication or a natural oral hygiene product for treatment of Candida-associated denture stomatitis. PMID:26962371

  4. [Presumptive identification of Candida spp. and other clinically important yeasts: usefulness of Brilliance Candida Agar].

    PubMed

    Alfonso, Claudia; López, Mónica; Arechavala, Alicia; Perrone, María Del Carmen; Guelfand, Liliana; Bianchi, Mario

    2010-06-30

    Fungal infections caused by yeasts have increased during the last decades and invasive forms represent a serious problem for human health. Candida albicans is the species most frequently isolated from clinical samples. However, other emerging yeast pathogens are increasingly responsible for mycotic infections, and some of them are resistant to some antifungal drugs. Consequently, it is necessary to have methods that can provide a rapid presumptive identification at species level. Numerous chromogenic agar media have been shown to be of value as diagnostic tools. We have compared a chromogenic medium, Brilliance Candida Agar, with CHROMagar Candida, the chromogenic medium most used in our country. A multicentre study was conducted in 16 Hospitals belonging to the Mycology Net of Buenos Aires City Government. A total of 240 yeast isolates were included in this research. The new chromogenic agar showed results very similar to those obtained with CHROMagar Candida.

  5. Presumptive identification of Candida species other than C. albicans, C. krusei, and C. tropicalis with the chromogenic medium CHROMagar Candida

    PubMed Central

    Hospenthal, Duane R; Beckius, Miriam L; Floyd, Karon L; Horvath, Lynn L; Murray, Clinton K

    2006-01-01

    Background CHROMagar Candida (CaC) is increasingly being reported as a medium used to differentiate Candida albicans from non-albicans Candida (NAC) species. Rapid identification of NAC can assist the clinician in selecting appropriate antifungal therapy. CaC is a differential chromogenic medium designed to identify C. albicans, C. krusei, and C. tropicalis based on colony color and morphology. Some reports have proposed that CaC can also reliably identify C. dubliniensis and C. glabrata. Methods We evaluated the usefulness of CaC in the identification of C. dubliniensis, C. famata, C. firmetaria, C. glabrata, C. guilliermondii, C. inconspicua, C. kefyr, C. lipolytica, C. lusitaniae, C. norvegensis, C. parapsilosis, and C. rugosa. Results Most NAC produced colonies that were shades of pink, lavender, or ivory. Several isolates of C. firmetaria and all C. inconspicua produced colonies difficult to differentiate from C. krusei. Most C. rugosa isolates produced unique colonies with morphology like C. krusei except in a light blue-green color. C. glabrata isolates produced small dark violet colonies that could be differentiated from the pink and lavender colors produced by other species. All seventeen isolates of C. dubliniensis produced green colonies similar to those produced by C. albicans. Conclusion C. glabrata and C. rugosa appear distinguishable from other species using CaC. Some NAC, including C. firmetaria and C. inconspicua, could be confused with C. krusei using this medium. PMID:16390552

  6. External ecological niche for Candida albicans within reducing, oxygen-limited zones of wetlands.

    PubMed

    Stone, Wendy; Jones, Barbara-Lee; Wilsenach, Jac; Botha, Alfred

    2012-04-01

    Candida albicans within the human host is well studied; however, identifying environmental reservoirs of pathogens is epidemiologically valuable for disease management. Oxygen-limited, carbohydrate-rich zones of wetlands, to which sewage-borne C. albicans is often exposed, are characteristically similar to the gastrointestinal reservoir. Consequently, using quantitative real-time PCR (qRT-PCR) and gas chromatography-mass spectrometry (GC-MS), we demonstrated that oxygen-limited zones in polluted wetlands may act as potential reservoirs of C. albicans.

  7. Host defence against Candida albicans and the role of pattern-recognition receptors.

    PubMed

    Gauglitz, Gerd G; Callenberg, Helene; Weindl, Günther; Korting, Hans C

    2012-05-01

    Recognition of Candida albicans is mediated by several classes of pattern-recognition receptors, including Toll-like receptors and C-type lectin receptors. Cell wall components of C. albicans, interact with the pattern-recognition receptors, which are expressed by different cells, primarily antigen-presenting cells. This review aims to discuss the different pattern-recognition receptors responsible for recognition of special structures of C. albicans, which are known to activate intracellular signals that finally lead to directed and efficient host defence.

  8. Potential Targets for Antifungal Drug Discovery Based on Growth and Virulence in Candida albicans

    PubMed Central

    Li, Xiuyun; Hou, Yinglong; Yue, Longtao; Liu, Shuyuan; Du, Juan

    2015-01-01

    Fungal infections, especially infections caused by Candida albicans, remain a challenging problem in clinical settings. Despite the development of more-effective antifungal drugs, their application is limited for various reasons. Thus, alternative treatments with drugs aimed at novel targets in C. albicans are needed. Knowledge of growth and virulence in fungal cells is essential not only to understand their pathogenic mechanisms but also to identify potential antifungal targets. This article reviews the current knowledge of the mechanisms of growth and virulence in C. albicans and examines potential targets for the development of new antifungal drugs. PMID:26195510

  9. Essential Oils, Silver Nanoparticles and Propolis as Alternative Agents Against Fluconazole Resistant Candida albicans, Candida glabrata and Candida krusei Clinical Isolates.

    PubMed

    Szweda, Piotr; Gucwa, Katarzyna; Kurzyk, Ewelina; Romanowska, Ewa; Dzierżanowska-Fangrat, Katarzyna; Zielińska Jurek, Anna; Kuś, Piotr Marek; Milewski, Sławomir

    2015-06-01

    Development of effective and safe therapeutic treatment of fungal infections remains one of the major challenge for modern medicine. The aim of presented investigation was to analyze the in vitro antifungal activity of selected essential oils, ethanolic extracts of propolis and silver nanoparticles dropped on TiO2 against azole-resistant C. albicans (n = 20), C. glabrata (n = 14) and C. krusei (n = 10) clinical isolates. Among tested essential oils, the highest activity has definitely been found in the case of the oil isolated from the bark of Cinnamomum cassia, with MIC and MFC values for all tested strains in the range of 0.0006-0.0097 % (v/v) and 0.0012-0.019 % (v/v), respectively. High activity was also observed for the Lemon, Basil, Thyme, Geranium and Clove (from buds) essential oils. Significant differences in fungicidal activity have been observed in the case of four tested propolis samples. Only one of them revealed high activity, with MFC values in the range from 0.156 to 1.25 % (v/v). Satisfactory fungicidal activity, against C. albicans and C. glabrata isolates, was also observed in the case of silver nanoparticles, however C. krusei isolates were mostly resistant. We also revealed that constituents of most of essential oils and propolis as well as silver nanoparticles are not substrates for drug transporters, which belong to the most important factors affecting resistance of Candida spp. clinical isolates to many of conventional antimycotics. To conclude, the results of our investigation revealed that essential oils, propolis and silver nanoparticles represent high potential for controlling and prevention candidiasis. PMID:25805904

  10. Essential Oils, Silver Nanoparticles and Propolis as Alternative Agents Against Fluconazole Resistant Candida albicans, Candida glabrata and Candida krusei Clinical Isolates.

    PubMed

    Szweda, Piotr; Gucwa, Katarzyna; Kurzyk, Ewelina; Romanowska, Ewa; Dzierżanowska-Fangrat, Katarzyna; Zielińska Jurek, Anna; Kuś, Piotr Marek; Milewski, Sławomir

    2015-06-01

    Development of effective and safe therapeutic treatment of fungal infections remains one of the major challenge for modern medicine. The aim of presented investigation was to analyze the in vitro antifungal activity of selected essential oils, ethanolic extracts of propolis and silver nanoparticles dropped on TiO2 against azole-resistant C. albicans (n = 20), C. glabrata (n = 14) and C. krusei (n = 10) clinical isolates. Among tested essential oils, the highest activity has definitely been found in the case of the oil isolated from the bark of Cinnamomum cassia, with MIC and MFC values for all tested strains in the range of 0.0006-0.0097 % (v/v) and 0.0012-0.019 % (v/v), respectively. High activity was also observed for the Lemon, Basil, Thyme, Geranium and Clove (from buds) essential oils. Significant differences in fungicidal activity have been observed in the case of four tested propolis samples. Only one of them revealed high activity, with MFC values in the range from 0.156 to 1.25 % (v/v). Satisfactory fungicidal activity, against C. albicans and C. glabrata isolates, was also observed in the case of silver nanoparticles, however C. krusei isolates were mostly resistant. We also revealed that constituents of most of essential oils and propolis as well as silver nanoparticles are not substrates for drug transporters, which belong to the most important factors affecting resistance of Candida spp. clinical isolates to many of conventional antimycotics. To conclude, the results of our investigation revealed that essential oils, propolis and silver nanoparticles represent high potential for controlling and prevention candidiasis.

  11. Antifungal mechanism of essential oil from Anethum graveolens seeds against Candida albicans.

    PubMed

    Chen, Yuxin; Zeng, Hong; Tian, Jun; Ban, Xiaoquan; Ma, Bingxin; Wang, Youwei

    2013-08-01

    This work studied the antifungal mechanism of dill seed essential oil (DSEO) against Candida albicans. Flow cytometric analysis and inhibition of ergosterol synthesis were performed to clarify the mechanism of action of DSEO on C. albicans. Upon treatment of cells with DSEO, propidium iodide penetrated C. albicans through a lesion in its plasma membrane. DSEO also significantly reduced the amount of ergosterol. These findings indicate that the plasma membrane of C. albicans was damaged by DSEO. The effect of DSEO on the functions of the mitochondria in C. albicans was also studied. We assayed the mitochondrial membrane potential (mtΔψ) using rhodamine 123 and determined the production of mitochondrial dysfunction-induced reactive oxygen species (ROS) via flow cytometry. The effects of the antioxidant l-cysteine (Cys) on DSEO-induced ROS production and the antifungal effect of DSEO on C. albicans were investigated. Exposure to DSEO increased mtΔψ. Dysfunctions in the mitochondria caused ROS accumulation in C. albicans. This increase in the level of ROS production and DSEO-induced decrease in cell viability were prevented by the addition of Cys, indicating that ROS are an important mediator of the antifungal action of DSEO. These findings indicate that the cytoplasmic membrane and mitochondria are the main anti-Candida targets of DSEO. PMID:23657528

  12. Growth of Candida albicans in human saliva is supported by low-molecular-mass compounds.

    PubMed

    Valentijn-Benz, Marianne; Nazmi, Kamran; Brand, Henk S; van't Hof, Wim; Veerman, Enno C I

    2015-12-01

    Saliva plays a key role in the maintenance of a stable oral microflora. It contains antimicrobial compounds but also functions as a substrate for growth of bacteria under conditions of low external nutrient supply. Besides bacteria, yeasts, in particular Candida albicans, commonly inhabit the oral cavity. Under immunocompromised conditions, instantaneous outgrowth of this yeast occurs in oral carriers of C. albicans, suggesting that this yeast is able to survive in the oral cavity with saliva as sole source of growth substrate. The aim of the present study was to identify the salivary constituents that are used by C. albicans for growth and survival in saliva. In addition, we have explored the effect of growth in saliva on the susceptibility of C. albicans to histatin 5, a salivary antifungal peptide. It was found that C. albicans was able to grow in human saliva without addition of glucose, and in the stationary phase could survive for more than 400 h. Candida albicans grown in saliva was more than 10 times less susceptible for salivary histatin 5 than C. albicans cultured in Sabouraud medium.

  13. Micafungin triggers caspase-dependent apoptosis in Candida albicans and Candida parapsilosis biofilms, including caspofungin non-susceptible isolates.

    PubMed

    Shirazi, F; Kontoyiannis, D P

    2015-01-01

    Candida biofilms play an important role in infections associated with medical devices and are resistant to antifungals. We hypothesized that the echinocandin micafungin (MICA) exerts an enhanced antifungal activity against caspofungin (CAS)-susceptible (CAS-S) and CAS-non-susceptible (CAS-NS) Candida albicans and Candida parapsilosis which is at least in part through apoptosis, even in the biofilm environment. Apoptosis was characterized by detecting reactive oxygen species (ROS) accumulation, depolarization of mitochondrial membrane potential (MMP), DNA fragmentation, lack of plasma membrane integrity, and metacaspase activation following exposure of Candida biofilm to MICA for 3h at 37°C in RPMI 1640 medium. The minimum inhibitory concentration was higher for CAS (2.0-16.0 μg/mL) than for MICA (1.0-8.0 μg/mL) for Candida biofilms. Elevated intracellular ROS levels and depolarization of MMP was evident in CAS-S C. albicans (3.0-4.2 fold) and C. parapsilosis (4.8-5.4 fold) biofilms compared with CAS-NS (1.2 fold) after exposure to MICA (0.25x-1xMIC). Elevated intracellular ROS levels and depolarization of MMP was evident in CAS-S C. albicans (3.0-4.2 fold) and C. parapsilosis (4.8-5.4 fold) biofilms compared with CAS-NS (1.2 fold) after exposure to MICA (0.25x-1xMIC). Finally higher ß-1, 3 glucan levels were seen in sessile cells compared to planktonic cells, especially in CAS-NS strains. MICA treatment might induce a metacaspase-dependent apoptotic process in biofilms of both CAS-S C. albicans and C. parapsilosis, and to some degree in CAS-NS strains.

  14. Effect of Nitric Oxide on the Antifungal Activity of Oxidative Stress and Azoles Against Candida albicans.

    PubMed

    Li, De-Dong; Yang, Chang-Chun; Liu, Ping; Wang, Yan; Sun, Yan

    2016-06-01

    Nitric oxide (NO) is a small molecule with a wide range of biological activities in mammalian and bacteria. However, the role of NO in fungi, especially Candida albicans, is not clear. In this study, we confirmed the generation of endogenous NO in C. albicans, and found that the production of endogenous NO in C. albicans was associated with nitric oxide synthase pathway. Our results further indicated that the production of endogenous NO in C. albicans was reduced under oxidative stress such as menadione or H2O2 treatment. Meanwhile, exogenous NO donor, sodium nitroprusside (SNP), synergized with H2O2 against C. albicans. Interestingly, SNP could inhibit the antifungal effect of azoles against C. albicans in vitro, suggesting that NO might be involved in the resistance of C. albicans to antifungals. Collectively, this study demonstrated the production of endogenous NO in C. albicans, and indicated that NO may play an important role in the response of C. albicans to oxidative stress and azoles. PMID:27570314

  15. Human Epithelial Cells Discriminate between Commensal and Pathogenic Interactions with Candida albicans.

    PubMed

    Rast, Timothy J; Kullas, Amy L; Southern, Peter J; Davis, Dana A

    2016-01-01

    The commensal fungus, Candida albicans, can cause life-threatening infections in at risk individuals. C. albicans colonizes mucosal surfaces of most people, adhering to and interacting with epithelial cells. At low concentrations, C. albicans is not pathogenic nor does it cause epithelial cell damage in vitro; at high concentrations, C. albicans causes mucosal infections and kills epithelial cells in vitro. Here we show that while there are quantitative dose-dependent differences in exposed epithelial cell populations, these reflect a fundamental qualitative difference in host cell response to C. albicans. Using transcriptional profiling experiments and real time PCR, we found that wild-type C. albicans induce dose-dependent responses from a FaDu epithelial cell line. However, real time PCR and Western blot analysis using a high dose of various C. albicans strains demonstrated that these dose-dependent responses are associated with ability to promote host cell damage. Our studies support the idea that epithelial cells play a key role in the immune system by monitoring the microbial community at mucosal surfaces and initiating defensive responses when this community is dysfunctional. This places epithelial cells at a pivotal position in the interaction with C. albicans as epithelial cells themselves promote C. albicans stimulated damage.

  16. Antimicrobial blue light therapy for Candida albicans burn infection in mice

    NASA Astrophysics Data System (ADS)

    Zhang, Yunsong; Wang, Yucheng; Murray, Clinton K.; Hamblin, Michael R.; Gu, Ying; Dai, Tianhong

    2015-05-01

    In this preclinical study, we investigated the utility of antimicrobial blue light therapy for Candida albicans infection in acutely burned mice. A bioluminescent strain of C. albicans was used. The susceptibilities to blue light inactivation were compared between C. albicans and human keratinocyte. In vitro serial passaging of C. albicans on blue light exposure was performed to evaluate the potential development of resistance to blue light inactivation. A mouse model of acute thermal burn injury infected with the bioluminescent strain of C. albicans was developed. Blue light (415 nm) was delivered to mouse burns for decolonization of C. albicans. Bioluminescence imaging was used to monitor in real time the extent of fungal infection in mouse burns. Experimental results showed that C. albicans was approximately 42-fold more susceptible to blue light inactivation in vitro than human keratinocyte (P=0.0022). Serial passaging of C. albicans on blue light exposure implied a tendency for the fungal susceptibility to blue light inactivation to decrease with the numbers of passages. Blue light reduced fungal burden by over 4-log10 (99.99%) in acute mouse burns infected with C. albicans in comparison to infected mouse burns without blue light therapy (P=0.015).

  17. Gene expression profile of THP-1 cells treated with heat-killed Candida albicans

    PubMed Central

    Hu, Zhi-De; Wei, Ting-Ting; Tang, Qing-Qin; Ma, Ning; Wang, Li-Li; Qin, Bao-Dong; Yin, Jian-Rong

    2016-01-01

    Background Mechanisms under immune response against Candida albicans (C. albicans) remain largely unknown. To better understand the mechanisms of innate immune response against C. albicans, we analyzed the gene expression profile of THP-1 cells stimulated with heat-killed C. albicans. Methods THP-1 cells were stimulated with heat-killed C. albicans for 9 hours at a ratio of 1:1, and gene expression profile of the cells was analyzed using Whole Human Genome Oligo Microarray. Differentially expressed genes were defined as change folds more than 2 and with statistical significance. Gene ontology (GO) and pathway analysis were used to systematically identify biological connections of differentially expressed genes, as well as the pathways associated with the immune response against C. albicans. Results A total of 355 genes were up-regulated and 715 genes were down-regulated significantly. The up-regulated genes were particularly involved in biological process of RNA processing and pathway of the spliceosome. In case of down-regulated genes, the particularly involved immune-related pathways were G-protein coupled receptor signaling pathway, calcium signaling pathway, MAPK signaling pathway and Ras pathway. Conclusions We depict the gene expression profile of heat-killed C. albicans stimulated THP-1 cells, and identify the major pathways involved in immune response against C. albicans. These pathways are potential candidate targets for developing anti-C. albicans agent. PMID:27275483

  18. Human Epithelial Cells Discriminate between Commensal and Pathogenic Interactions with Candida albicans

    PubMed Central

    Rast, Timothy J.; Kullas, Amy L.; Southern, Peter J.; Davis, Dana A.

    2016-01-01

    The commensal fungus, Candida albicans, can cause life-threatening infections in at risk individuals. C. albicans colonizes mucosal surfaces of most people, adhering to and interacting with epithelial cells. At low concentrations, C. albicans is not pathogenic nor does it cause epithelial cell damage in vitro; at high concentrations, C. albicans causes mucosal infections and kills epithelial cells in vitro. Here we show that while there are quantitative dose-dependent differences in exposed epithelial cell populations, these reflect a fundamental qualitative difference in host cell response to C. albicans. Using transcriptional profiling experiments and real time PCR, we found that wild-type C. albicans induce dose-dependent responses from a FaDu epithelial cell line. However, real time PCR and Western blot analysis using a high dose of various C. albicans strains demonstrated that these dose-dependent responses are associated with ability to promote host cell damage. Our studies support the idea that epithelial cells play a key role in the immune system by monitoring the microbial community at mucosal surfaces and initiating defensive responses when this community is dysfunctional. This places epithelial cells at a pivotal position in the interaction with C. albicans as epithelial cells themselves promote C. albicans stimulated damage. PMID:27088599

  19. Liposomal thymoquinone effectively combats fluconazole-resistant Candida albicans in a murine model.

    PubMed

    Khan, Masood Alam; Aljarbou, Ahmad N; Khan, Arif; Younus, Hina

    2015-05-01

    The aim of the present study was to develop a novel liposomal formulation of thymoquinone (TQ) to treat fluconazole-susceptible and -resistant Candida albicans (C. albicans) infections. The liposomal preparation of TQ (Lip-TQ) was used against a fluconazole-susceptible or -resistant isolate of C. albicans. Various doses of fluconazole (0, 5, 10, 20 and 40 mg/kg) or free TQ or Lip-TQ (0, 1, 2 and 5mg/kg) were used to treat C. albicans infected mice. Mice were observed for 40 days post C. albicans infection, and their kidneys were assessed for the fungal load. Fluconazole showed anti-fungal activity against the drug-susceptible, but not against the -resistant isolate of C. albicans. Free TQ showed its activity against both fluconazole-susceptible or -resistant C. albicans, however, Lip-TQ was found to be the most effective and imparted ∼ 100% and ∼ 90% survival of mice infected with fluconazole-susceptible and -resistant isolates of C. albicans, respectively. Mice treated with Lip-TQ showed highly reduced severity of infection in their tissue homogenates. Therefore, Lip-TQ may effectively be used in the treatment of C. albicans infections, including those which are not responding to fluconazole.

  20. Human Epithelial Cells Discriminate between Commensal and Pathogenic Interactions with Candida albicans.

    PubMed

    Rast, Timothy J; Kullas, Amy L; Southern, Peter J; Davis, Dana A

    2016-01-01

    The commensal fungus, Candida albicans, can cause life-threatening infections in at risk individuals. C. albicans colonizes mucosal surfaces of most people, adhering to and interacting with epithelial cells. At low concentrations, C. albicans is not pathogenic nor does it cause epithelial cell damage in vitro; at high concentrations, C. albicans causes mucosal infections and kills epithelial cells in vitro. Here we show that while there are quantitative dose-dependent differences in exposed epithelial cell populations, these reflect a fundamental qualitative difference in host cell response to C. albicans. Using transcriptional profiling experiments and real time PCR, we found that wild-type C. albicans induce dose-dependent responses from a FaDu epithelial cell line. However, real time PCR and Western blot analysis using a high dose of various C. albicans strains demonstrated that these dose-dependent responses are associated with ability to promote host cell damage. Our studies support the idea that epithelial cells play a key role in the immune system by monitoring the microbial community at mucosal surfaces and initiating defensive responses when this community is dysfunctional. This places epithelial cells at a pivotal position in the interaction with C. albicans as epithelial cells themselves promote C. albicans stimulated damage. PMID:27088599

  1. Photodynamic Inactivation of Candida albicans with Imidazoacridinones: Influence of Irradiance, Photosensitizer Uptake and Reactive Oxygen Species Generation.

    PubMed

    Taraszkiewicz, Aleksandra; Szewczyk, Grzegorz; Sarna, Tadeusz; Bielawski, Krzysztof P; Nakonieczna, Joanna

    2015-01-01

    The increasing applicability of antifungal treatments, the limited range of available drug classes and the emergence of drug resistance in Candida spp. suggest the need for new treatment options. To explore the applicability of C. albicans photoinactivation, we examined nine structurally different imidazoacridinone derivatives as photosensitizing agents. The most effective derivatives showed a >10(4)-fold reduction of viable cell numbers. The fungicidal action of the three most active compounds was compared at different radiant powers (3.5 to 63 mW/cm2), and this analysis indicated that 7 mW/cm2 was the most efficient. The intracellular accumulation of these compounds in fungal cells correlated with the fungicidal activity of all 9 derivatives. The lack of effect of verapamil, an inhibitor targeting Candida ABC efflux pumps, suggests that these imidazoacridinones are not substrates for ABC transporters. Thus, unlike azoles, a major class of antifungals used against Candida, ABC transporter-mediated resistance is unlikely. Electron paramagnetic resonance (EPR)-spin trapping data suggested that the fungicidal light-induced action of these derivatives might depend on the production of superoxide anion. The highest generation rate of superoxide anion was observed for 1330H, 1610H, and 1611. Singlet oxygen production was also detected upon the irradiation of imidazoacridinone derivatives with UV laser light, with a low to moderate yield, depending on the type of compound. Thus, imidazoacridinone derivatives examined in the present study might act via mixed type I/type II photodynamic mechanism. The presented data indicate lack of direct correlation between the structures of studied imidazoacridinones, cell killing ability, and ROS production. However, we showed for the first time that for imidazoacridinones not only intracellular accumulation is necessary prerequisite of lethal photosensitization of C. albicans, but also localization within particular cellular

  2. Photodynamic Inactivation of Candida albicans with Imidazoacridinones: Influence of Irradiance, Photosensitizer Uptake and Reactive Oxygen Species Generation.

    PubMed

    Taraszkiewicz, Aleksandra; Szewczyk, Grzegorz; Sarna, Tadeusz; Bielawski, Krzysztof P; Nakonieczna, Joanna

    2015-01-01

    The increasing applicability of antifungal treatments, the limited range of available drug classes and the emergence of drug resistance in Candida spp. suggest the need for new treatment options. To explore the applicability of C. albicans photoinactivation, we examined nine structurally different imidazoacridinone derivatives as photosensitizing agents. The most effective derivatives showed a >10(4)-fold reduction of viable cell numbers. The fungicidal action of the three most active compounds was compared at different radiant powers (3.5 to 63 mW/cm2), and this analysis indicated that 7 mW/cm2 was the most efficient. The intracellular accumulation of these compounds in fungal cells correlated with the fungicidal activity of all 9 derivatives. The lack of effect of verapamil, an inhibitor targeting Candida ABC efflux pumps, suggests that these imidazoacridinones are not substrates for ABC transporters. Thus, unlike azoles, a major class of antifungals used against Candida, ABC transporter-mediated resistance is unlikely. Electron paramagnetic resonance (EPR)-spin trapping data suggested that the fungicidal light-induced action of these derivatives might depend on the production of superoxide anion. The highest generation rate of superoxide anion was observed for 1330H, 1610H, and 1611. Singlet oxygen production was also detected upon the irradiation of imidazoacridinone derivatives with UV laser light, with a low to moderate yield, depending on the type of compound. Thus, imidazoacridinone derivatives examined in the present study might act via mixed type I/type II photodynamic mechanism. The presented data indicate lack of direct correlation between the structures of studied imidazoacridinones, cell killing ability, and ROS production. However, we showed for the first time that for imidazoacridinones not only intracellular accumulation is necessary prerequisite of lethal photosensitization of C. albicans, but also localization within particular cellular

  3. Prospective evaluation of the chromogenic medium CandiSelect 4 for differentiation and presumptive identification of non-Candida albicans Candida species.

    PubMed

    Zhao, Liang; de Hoog, G Sybren; Cornelissen, Akke; Lyu, Qian; Mou, Lili; Liu, Taohua; Cao, Yu; Vatanshenassan, Mansoureh; Kang, Yingqian

    2016-02-01

    Rapid identification of pathogenic yeasts is a crucial step in timely and appropriate antifungal therapy. For diagnostics in the clinical laboratory, simplified alternatives to barcoding are needed. CandiSelect 4 (CS4) medium, a chromogenic medium for isolation of clinical yeasts, allows routine recognition of Candida albicans and presumptive identification of Candida tropicalis, Candida glabrata, and Candida krusei. We evaluated an extension of this method with 46 non-Candida albicans Candida (NCAC) and 7 Malassezia species. The medium supported growth of all species tested and a wide diversity of cultural types were observed. Colony colours were in violet, turquoise (including green and blue), or white tinges. Eight NCAC species produced violet pigmentation similar to that of C. albicans. Most NCAC species, including C. glabrata and C. tropicalis were distributed in the turquoise group. Malassezia species were invariably blue.

  4. Prospective evaluation of the chromogenic medium CandiSelect 4 for differentiation and presumptive identification of non-Candida albicans Candida species.

    PubMed

    Zhao, Liang; de Hoog, G Sybren; Cornelissen, Akke; Lyu, Qian; Mou, Lili; Liu, Taohua; Cao, Yu; Vatanshenassan, Mansoureh; Kang, Yingqian

    2016-02-01

    Rapid identification of pathogenic yeasts is a crucial step in timely and appropriate antifungal therapy. For diagnostics in the clinical laboratory, simplified alternatives to barcoding are needed. CandiSelect 4 (CS4) medium, a chromogenic medium for isolation of clinical yeasts, allows routine recognition of Candida albicans and presumptive identification of Candida tropicalis, Candida glabrata, and Candida krusei. We evaluated an extension of this method with 46 non-Candida albicans Candida (NCAC) and 7 Malassezia species. The medium supported growth of all species tested and a wide diversity of cultural types were observed. Colony colours were in violet, turquoise (including green and blue), or white tinges. Eight NCAC species produced violet pigmentation similar to that of C. albicans. Most NCAC species, including C. glabrata and C. tropicalis were distributed in the turquoise group. Malassezia species were invariably blue. PMID:26781374

  5. Altered hepatic clearance and killing of Candida albicans in the isolated perfused mouse liver model.

    PubMed

    Sawyer, R T; Horst, M N; Garner, R E; Hudson, J; Jenkins, P R; Richardson, A L

    1990-09-01

    The adherence of Candida albicans was studied in situ by using the perfused mouse liver model. After exhaustive washing, 10(6) C. albicans were infused into mouse livers. At the time of recovery, 62 +/- 5% (mean +/- standard error of the mean) of the infused C. albicans were recovered from the liver and 14 +/- 3% were recovered from the effluent for a total recovery of 76 +/- 4%. This indicates that 86 +/- 3% of the original inoculum was trapped by the liver and that 24 +/- 4% was killed within the liver. Chemical pretreatment of C. albicans with 8 M urea, 12 mM dithiothreitol, 2% beta-mercaptoethanol, 1% sodium dodecyl sulfate, 10% Triton X-100, or 3 M potassium chloride or enzyme pretreatment with alpha-mannosidase, alpha-chymotrypsin, subtilisin, beta-N-acetyl-glucosaminidase, pronase, trypsin, papain, or lipase did not alter adherence of C. albicans to hepatic tissue. By contrast, pepsin pretreatment significantly decreased hepatic trapping. Simultaneous perfusion with either 100 mg of C. albicans glycoprotein per liter or 100 mg of C. albicans mannan per liter also decreased trapping. Furthermore, both substances eluted previously trapped C. albicans from hepatic tissue. Chemical pretreatment with 8 M urea, 12 mM dithiothreitol, or 3 M KCI or enzymatic pretreatment with alpha-mannosidase, subtilisin, alpha-chymotrypsin, or papain increased killing of C. albicans three- to fivefold within hepatic tissue. The data suggest that mannose-containing structures on the surface of C. albicans, for example. mannans or glucomannoproteins, mediate adherence of C. albicans within the liver. Indirectly, chemical and enzymatic pretreatment renders C. albicans more susceptible to hepatic killing.

  6. Candida albicans Shaving to Profile Human Serum Proteins on Hyphal Surface

    PubMed Central

    Marín, Elvira; Parra-Giraldo, Claudia M.; Hernández-Haro, Carolina; Hernáez, María L.; Nombela, César; Monteoliva, Lucía; Gil, Concha

    2015-01-01

    Candida albicans is a human opportunistic fungus and it is responsible for a wide variety of infections, either superficial or systemic. C. albicans is a polymorphic fungus and its ability to switch between yeast and hyphae is essential for its virulence. Once C. albicans obtains access to the human body, the host serum constitutes a complex environment of interaction with C. albicans cell surface in bloodstream. To draw a comprehensive picture of this relevant step in host-pathogen interaction during invasive candidiasis, we have optimized a gel-free shaving proteomic strategy to identify both, human serum proteins coating C. albicans cells and fungi surface proteins simultaneously. This approach was carried out with normal serum (NS) and heat inactivated serum (HIS). We identified 214 human and 372 C. albicans unique proteins. Proteins identified in C. albicans included 147 which were described as located at the cell surface and 52 that were described as immunogenic. Interestingly, among these C. albicans proteins, we identified 23 GPI-anchored proteins, Gpd2 and Pra1, which are involved in complement system evasion and 7 other proteins that are able to attach plasminogen to C. albicans surface (Adh1, Eno1, Fba1, Pgk1, Tdh3, Tef1, and Tsa1). Furthermore, 12 proteins identified at the C. albicans hyphae surface induced with 10% human serum were not detected in other hypha-induced conditions. The most abundant human proteins identified are involved in complement and coagulation pathways. Remarkably, with this strategy, all main proteins belonging to complement cascades were identified on the C. albicans surface. Moreover, we identified immunoglobulins, cytoskeletal proteins, metabolic proteins such as apolipoproteins and others. Additionally, we identified more inhibitors of complement and coagulation pathways, some of them serpin proteins (serine protease inhibitors), in HIS vs. NS. On the other hand, we detected a higher amount of C3 at the C. albicans surface in

  7. A single strain of Candida albicans associated with separate episodes of fungemia and meningitis.

    PubMed Central

    Porter, S D; Noble, M A; Rennie, R

    1996-01-01

    Four isolates of Candida albicans recovered from the blood and cerebral spinal fluid of a 66-year-old man during episodes of systemic infection separated by 3 months and antifungal therapy were analyzed by a variety of molecular typing methods. All four isolates were shown to represent the same strain, indicating a relapse of infection rather than reinfection. PMID:8784598

  8. Cerebral macroabscess caused by Candida albicans in an immunocompetent patient: A diagnostic challenge

    PubMed Central

    Figueiredo, Sônia M.; Campolina, Sabrina; Rosa, Carlos A.; Gontijo, Marcus; Tirone, Thelma; Assunção, Claudia B.; Freire, Tarcísio F.A.; Christo, Paulo P.; Caligiorne, Rachel B.

    2014-01-01

    We describe the history of a 24-year-old immunocompetent man with an expansive lesion in the brainstem that, after many misdiagnoses, was found to be caused by a Candida albicans abscess. One year after surgery and 3 months of fluconazole treatment, the patient was asymptomatic and all image and laboratory tests were normal. PMID:24567895

  9. Comparative Susceptibility of Candida albicans to Amphotericin B and Amphotericin B Methyl Ester

    PubMed Central

    Bannatyne, Robert M.; Cheung, Rose

    1977-01-01

    The in vitro antifungal activities of amphotericin B (AMB) and amphotericin B methyl ester (AME) were compared against 465 clinical isolates of Candida albicans. AMB and AME possessed comparable activity against half of the strains, but against the remainder of the strains the activity of AME was slightly lower than that of AMB. Rarely did AME show superior antifungal activity to AMB. PMID:335958

  10. Effect of surface treatments of porcelain on adhesion of Candida albicans.

    PubMed

    Lawaf, Shirin; Azizi, Arash; Farzad, Azin; Adimi, Parvaneh

    2016-01-01

    Surface treatment of porcelain is required to minimize the adhesion of microorganisms to surfaces of the restoration. This study sought to assess the effects of 3 different porcelain surface treatments on adhesion of Candida albicans. This in vitro experimental study was conducted on 60 porcelain disks (10 × 3 mm) randomly divided into 4 groups of 15. The nonglazed group received no surface treatment; specimens in the other 3 groups were glazed in the furnace, overglazed with liquid glaze, or polished using a polishing kit. The specimens were washed, sterilized, and separately incubated with 350 µL of Candida albicans suspension for 24 hours. Specimens were then rinsed for 20 seconds and shaken in 1 mL of saline solution for 1 minute, and 20 µL of this suspension was cultured in a plate and incubated at 37°C for 48 hours. Candida albicans colonies were counted to assess the number of microorganisms adhering to each disk. Data were analyzed with the Kruskal-Wallis test. Statistically significant differences were found among the 4 groups in terms of C albicans adherence (P = 0.001). The nonglazed porcelain had the highest and the overglazed porcelain had the lowest mean adherence value. No statistically significant difference was noted between glazed and polished specimens. Based on the obtained results, overglazing resulted in the least adhesion of C albicans, and polishing provided a surface as smooth as a glazed surface. PMID:27367639

  11. Virulence and pathogenicity of Candida albicans is enhanced in biofilms containing oral bacteria.

    PubMed

    Cavalcanti, Yuri Wanderley; Morse, Daniel James; da Silva, Wander José; Del-Bel-Cury, Altair Antoninha; Wei, Xiaoqing; Wilson, Melanie; Milward, Paul; Lewis, Michael; Bradshaw, David; Williams, David Wynne

    2015-01-01

    This study examined the influence of bacteria on the virulence and pathogenicity of candidal biofilms. Mature biofilms (Candida albicans-only, bacteria-only, C. albicans with bacteria) were generated on acrylic and either analysed directly, or used to infect a reconstituted human oral epithelium (RHOE). Analyses included Candida hyphae enumeration and assessment of Candida virulence gene expression. Lactate dehydrogenase (LDH) activity and Candida tissue invasion following biofilm infection of the RHOE were also measured. Candida hyphae were more prevalent (p < 0.05) in acrylic biofilms also containing bacteria, with genes encoding secreted aspartyl-proteinases (SAP4/SAP6) and hyphal-wall protein (HWP1) up-regulated (p < 0.05). Candida adhesin genes (ALS3/EPA1), SAP6 and HWP1 were up-regulated in mixed-species biofilm infections of RHOE. Multi-species infections exhibited higher hyphal proportions (p < 0.05), up-regulation of IL-18, higher LDH activity and tissue invasion. As the presence of bacteria in acrylic biofilms promoted Candida virulence, consideration should be given to the bacterial component when managing denture biofilm associated candidoses.

  12. Antifungal activity of silver nanoparticles in combination with nystatin and chlorhexidine digluconate against Candida albicans and Candida glabrata biofilms.

    PubMed

    Monteiro, Douglas R; Silva, Sónia; Negri, Melyssa; Gorup, Luiz F; de Camargo, Emerson R; Oliveira, Rosário; Barbosa, Debora B; Henriques, Mariana

    2013-11-01

    Although silver nanoparticles (SN) have been investigated as an alternative to conventional antifungal drugs in the control of Candida-associated denture stomatitis, the antifungal activity of SN in combination with antifungal drugs against Candida biofilms remains unknown. Therefore, the aim of this study was to evaluate the antifungal efficacy of SN in combination with nystatin (NYT) or chlorhexidine digluconate (CHG) against Candida albicans and Candida glabrata biofilms. The drugs alone or combined with SN were applied on mature Candida biofilms (48 h), and after 24 h of treatment their antibiofilm activities were assessed by total biomass quantification (by crystal violet staining) and colony forming units enumeration. The structure of Candida biofilms was analysed by scanning electron microscopy (SEM) images. The data indicated that SN combined with either NYT or CHG demonstrated synergistic antibiofilm activity, and this activity was dependent on the species and on the drug concentrations used. SEM images showed that some drug combinations were able to disrupt Candida biofilms. The results of this study suggest that the combination of SN with NYT or CHG may have clinical implications in the treatment of denture stomatitis. However, further studies are needed before recommending the use of these drugs safely in clinical situations. PMID:23773119

  13. Evaluation of Candida albicans formation on feldspathic porcelain subjected to four surface treatment methods.

    PubMed

    Karayazgan, Banu; Atay, Arzu; Saracli, Mehmet Ali; Gunay, Yumushan

    2010-03-01

    Candida albicans, known for its adhesion on prosthetic materials and oral tissues, is the most frequently encountered fungal infection in dentistry. The aim of this study was to evaluate the effects of four different surface treatment methods and immersion in artificial saliva on the surface roughness of and candida adhesion on dental porcelains. The four surface treatment methods were namely: natural glaze, overglaze, dual ion exchange, and polishing. Surface roughness of porcelain was evaluated using a surface profilometer and by SEM. Candida adhesion was examined by culturing two Candida strains on porcelain specimens followed by a colorimetric method using XTT/Coenzyme Q0. It became evident that Candida adhesion was found more in the specimens treated with natural glaze and polishing. Further, by the visual inspection of SEM images and comparison of surface roughness, polished and natural-glazed specimens showed rougher surface characteristics than overglazed and dual-ion-exchanged specimens. PMID:20379024

  14. IL-33 Priming Enhances Peritoneal Macrophage Activity in Response to Candida albicans.

    PubMed

    Tran, Vuvi G; Cho, Hong R; Kwon, Byungsuk

    2014-08-01

    IL-33 is a member of the IL-1 cytokine family and plays a role in the host defense against bacteria, viruses, and fungi. In this study, we investigated the function of IL-33 and its receptor in in vitro macrophage responses to Candida albicans. Our results demonstrate that pre-sensitization of isolated peritoneal macrophages with IL-33 enhanced their pro-inflammatory cytokine production and phagocytic activity in response to C. albicans. These macrophage activities were entirely dependent on the ST2-MyD88 signaling pathway. In addition, pre-sensitization with IL-33 also increased ROS production and the subsequent killing ability of macrophages following C. albicans challenge. These results indicate that IL-33 may increase anti-fungal activity against Candida through macrophage-mediated resistance mechanisms. PMID:25177252

  15. Evaluation of the new chromogenic medium Candida ID 2 for isolation and identification of Candida albicans and other medically important Candida species.

    PubMed

    Eraso, Elena; Moragues, María D; Villar-Vidal, María; Sahand, Ismail H; González-Gómez, Nagore; Pontón, José; Quindós, Guillermo

    2006-09-01

    The usefulness of Candida ID 2 (CAID2) reformulated medium (bioMérieux, France) has been compared with that of the former Candida ID (CAID; bioMérieux), Albicans ID 2 (ALB2; bioMérieux), and CHROMagar Candida (CAC; Chromagar, France) chromogenic media for the isolation and presumptive identification of clinically relevant yeasts. Three hundred forty-five stock strains from culture collections, and 103 fresh isolates from different clinical specimens were evaluated. CAID2 permitted differentiation based on colony color between Candida albicans (cobalt blue; sensitivity, 91.7%; specificity, 97.2%) and Candida dubliniensis (turquoise blue; sensitivity, 97.9%; specificity, 96.6%). Candida tropicalis gave distinguishable pink-bluish colonies in 97.4% of the strains in CAID2 (sensitivity, 97.4%; specificity, 100%); the same proportion was reached in CAC, where colonies were blue-gray (sensitivity, 97.4%; specificity, 98.7%). CAC and CAID2 showed 100% sensitivity values for the identification of Candida krusei. However, with CAID2, experience is required to differentiate the downy aspect of the white colonies of C. krusei from other white-colony-forming species. The new CAID2 medium is a good candidate to replace CAID and ALB2, and it compares well to CAC for culture and presumptive identification of clinically relevant Candida species. CAID2 showed better results than CAC in some aspects, such as quicker growth and color development of colonies from clinical specimens, detection of mixed cultures, and presumptive differentiation between C. albicans and C. dubliniensis.

  16. Evaluation of the new chromogenic medium Candida ID 2 for isolation and identification of Candida albicans and other medically important Candida species.

    PubMed

    Eraso, Elena; Moragues, María D; Villar-Vidal, María; Sahand, Ismail H; González-Gómez, Nagore; Pontón, José; Quindós, Guillermo

    2006-09-01

    The usefulness of Candida ID 2 (CAID2) reformulated medium (bioMérieux, France) has been compared with that of the former Candida ID (CAID; bioMérieux), Albicans ID 2 (ALB2; bioMérieux), and CHROMagar Candida (CAC; Chromagar, France) chromogenic media for the isolation and presumptive identification of clinically relevant yeasts. Three hundred forty-five stock strains from culture collections, and 103 fresh isolates from different clinical specimens were evaluated. CAID2 permitted differentiation based on colony color between Candida albicans (cobalt blue; sensitivity, 91.7%; specificity, 97.2%) and Candida dubliniensis (turquoise blue; sensitivity, 97.9%; specificity, 96.6%). Candida tropicalis gave distinguishable pink-bluish colonies in 97.4% of the strains in CAID2 (sensitivity, 97.4%; specificity, 100%); the same proportion was reached in CAC, where colonies were blue-gray (sensitivity, 97.4%; specificity, 98.7%). CAC and CAID2 showed 100% sensitivity values for the identification of Candida krusei. However, with CAID2, experience is required to differentiate the downy aspect of the white colonies of C. krusei from other white-colony-forming species. The new CAID2 medium is a good candidate to replace CAID and ALB2, and it compares well to CAC for culture and presumptive identification of clinically relevant Candida species. CAID2 showed better results than CAC in some aspects, such as quicker growth and color development of colonies from clinical specimens, detection of mixed cultures, and presumptive differentiation between C. albicans and C. dubliniensis. PMID:16954270

  17. Antifungal Effect of Zataria multiflora Essence on Experimentally Contaminated Acryl Resin Plates With Candida albicans

    PubMed Central

    Jafari, Abbas Ali; Falah Tafti, Abbas; Hoseiny, Seyed Mehdi; Kazemi, Abdolhossein

    2015-01-01

    Background: Adherence and colonization of Candida species particularly C. albicans on denture surfaces, forms a microbial biofilm, which may result denture stomatitis in complete denture users. Objectives: The purpose of the present study was to evaluate the antifungal effect Zataria multiflora essence in removing of Candida albicans biofilms on experimentally contaminated resin acryl plates. Materials and Methods: In the present experimental study, 160 resin acrylic plates (10 × 10 × 1 mm) were contaminated by immersion in 1 × 103 C. albicans suspension for 24 hours to prepare experimental Candida biofilms. The total number of Candida cells, which adhered to 20 randomly selected acryl resin plates was determined as the Candia load before cleaning. The remaining 140 plates were divided to seven groups of 20 and immersed in five concentrations of Zataria multiflora essence from 50 to 3.125 mg/mL as test, 100000 IU nystatin as the positive and sterile physiologic serum as the negative control. The remaining Candida cells on each acryl plate were also enumerated and data were analyzed using the SPSS 16 software with Kruskal-Wallis and Wilcoxon tests. Results: Zataria essence at concentrations of 50 and 25 mg/mL removed 100% of attached Candida cells similar to nystatine (MFC), while weaker Zataria essence solutions cleaned 88%, 60.5% and 44.7% of attached Candida cells. Kruskal-wallis test showed a statistically significant difference between all test groups (P = 0.0001). In this study 12.5 mg/mL concentration of Zataria multiflora was considered as the minimum inhibitory concentration (MIC90). Conclusions: Zataria essence, at concentrations of 50 and 25 mg/mL, effectively removed Candida cells that had adhered to the denture surface, similar to the level of removal observed for 100000 IU nystatin. PMID:25763273

  18. The correlation of virulence, pathogenicity, and itraconazole resistance with SAP activity in Candida albicans strains.

    PubMed

    Feng, Wenli; Yang, Jing; Pan, Yanwei; Xi, Zhiqin; Qiao, Zusha; Ma, Yan

    2016-02-01

    The relationship between SAP2 activity and drug resistance in Candida albicans was investigated by using itraconazole-resistant and itraconazole-sensitive C. albicans isolates. The precipitation zones were measured to analyze SAP2 activity. Mice were classified into itraconazole-resistant and -sensitive C. albicans isolate groups, and a control group, with their survival and mortality rate being observed over 30 days. The relative expression levels of CDR1, CDR2, MDR1, and SAP2 were measured using RT-PCR. It was found that the secreted aspartyl proteinase activity of itraconazole-resistant C. albicans strains was significantly higher than that of itraconazole-sensitive C. albicans strains (P < 0.001). A significantly higher mortality rate was recorded for mice treated with itraconazole-resistant C. albicans than for mice treated with itraconazole-sensitive C. albicans. In regards to the CDR1, CDR2, and MDR1 genes, there was no significant difference between the 2 groups of mice. Positive correlations between SAP2 and MDR1 and between CDR1 and CDR2 were found. The high expression level of SAP2 may relate to the virulence, pathogenicity, and resistance of C. albicans.

  19. Time-course proteomic profile of Candida albicans during adaptation to a fetal serum.

    PubMed

    Aoki, Wataru; Ueda, Tomomi; Tatsukami, Yohei; Kitahara, Nao; Morisaka, Hironobu; Kuroda, Kouichi; Ueda, Mitsuyoshi

    2013-02-01

    Candida albicans is a commensal organism; however, it causes fatal diseases if the host immunity is compromised. The mortality rate is very high due to the lack of effective treatment, leading to ceaseless demand for novel pharmaceuticals. In this study, time-course proteomics of C. albicans during adaptation to fetal bovine serum (FBS) was described. Time-course proteomics is a promising way to understand the exact process of going adaptation in dynamically changing environments. Candida albicans was cultivated in yeast nitrogen base (YNB) ± FBS media, and we identified 1418 proteins in the endpoint samples incubated for 0 or 60 min by a LC-MS/MS system with a long monolithic silica capillary column. Next, we carried out time-course proteomics of the YNB + FBS samples to identify top-priority proteins for adaption to FBS. We identified 16 proteins as nascent/newly synthesized proteins, and they were recognized as candidates of important virulent factors. Gene ontology analysis revealed that transport-related proteins were enriched in the 16 proteins, indicating that C. albicans probably put priority in time on the acquisition of essential elements. Time-course proteomics of C. albicans revealed the order of priority to adapt to FBS. Depicting time-course dynamics will lead to profound understandings of virulence of C. albicans. PMID:23620121

  20. [Evaluation of a new chromogenic medium (Candida ID) for the isolation and presumptive identification of Candida albicans and other medically important yeasts].

    PubMed

    Quindós, G; Alonso-Vargas, R; Helou, S; Arechavala, A; Martín-Mazuelos, E; Negroni, R

    2001-03-01

    Candidiasis is a frequent human infection caused mainly by Candida albicans. However, other species are emerging as important pathogens, as Candida glabrata, Candida parapsilosis, Candida tropicalis, Candida krusei or Candida guilliermondii. Rapid identification of clinical isolates could facilitate diagnosis and treatment. Candida ID (bioMerieux, Spain) is a new medium for the isolation and presumptive identification of yeasts: C. albicans grows as blue colonies, and C. tropicalis, C. guilliermondii, Candida kefyr and Candida lusitaniae as pink ones. The utility of Candida ID was evaluated with more than 700 clinical isolates and type culture collection strains from different genera including Candida, Cryptococcus, Saccharomyces, and Rhodotorula. Presumptive identification was confirmed by germ tube test, microscopic morphology and chlamydoconidia production on corn meal agar and carbohydrate assimilation on API-ATB ID 32C or Vitek (bioMerieux). Growth on Candida ID was rapid (18-24 h) for most of the yeast strains tested. Sensitivity and specificity of identification of C. albicans was significantly high (>98%), since a very low number of isolates were found to be false negative or false positive. A better result was obtained for species growing as pink colonies (>99.5%). Detection of different species of medical important yeasts was easy with Candida ID, as perfectly distinct colors and textures of colonies were observed on this medium. Candida ID allowed the discrimination between C. glabrata (creamy and smooth) and C. krusei (rough and white) colonies. Other species showed different colony textures and colours, white being the predominant colour. Candida ID was very useful for the presumptive identification C. albicans isolates.

  1. Hydrophobic properties of Candida spp. under the influence of selected essential oils.

    PubMed

    Rajkowska, Katarzyna; Kunicka-Styczyńska, Alina; Pęczek, Marlena

    2015-01-01

    Processes of colonization of biotic and abiotic surfaces and biofilm formation depend inter alia on hydrophobic properties of Candida spp. The aim of this research was to determine the effect of tea tree, thyme and clove essential oils on hydrophobic properties of environmental and clinical Candida isolates. The relative cell surface hydrophobicity of strains tested was high, and ranged from 68.7% to 91.2%, with the highest value for a C. rugosa food-borne strain. The effectiveness of essential oils was diversified and depended on the type of essential oil, concentration and yeast strain. Statistically significant decrease of hydrophobicity indexes was observed after application of tea tree oil for C. krusei, clove oil for C. albicans reference strain, and all essential oils tested for C. rugosa. Only in the case of C. famata food-borne strain and C. albicans clinical isolate, solely used essential oils did not affect their hydrophobic properties. To determine the interactions of essential oils, their mixtures (1 MIC:1 MIC, 1 MIC:2 MIC and 2 MIC:1 MIC) were applied. Generally, essential oils used in combinations influenced yeast's hydrophobic properties much more than applied separately. The essential oils' mixtures reduced hydrophobicity of Candida yeasts in the range of 8.2 to 45.1%, depending on combination and strain. The interaction indexes of essential oils used in combinations predominantly indicate their additive effect. The application of tea tree, thyme and clove essential oils, especially in combinations, decreases hydrophobicity of the tested Candida isolates with implications of a probable advantageous limitation of their ability to colonize the food production industry environment.

  2. Hydrophobic properties of Candida spp. under the influence of selected essential oils.

    PubMed

    Rajkowska, Katarzyna; Kunicka-Styczyńska, Alina; Pęczek, Marlena

    2015-01-01

    Processes of colonization of biotic and abiotic surfaces and biofilm formation depend inter alia on hydrophobic properties of Candida spp. The aim of this research was to determine the effect of tea tree, thyme and clove essential oils on hydrophobic properties of environmental and clinical Candida isolates. The relative cell surface hydrophobicity of strains tested was high, and ranged from 68.7% to 91.2%, with the highest value for a C. rugosa food-borne strain. The effectiveness of essential oils was diversified and depended on the type of essential oil, concentration and yeast strain. Statistically significant decrease of hydrophobicity indexes was observed after application of tea tree oil for C. krusei, clove oil for C. albicans reference strain, and all essential oils tested for C. rugosa. Only in the case of C. famata food-borne strain and C. albicans clinical isolate, solely used essential oils did not affect their hydrophobic properties. To determine the interactions of essential oils, their mixtures (1 MIC:1 MIC, 1 MIC:2 MIC and 2 MIC:1 MIC) were applied. Generally, essential oils used in combinations influenced yeast's hydrophobic properties much more than applied separately. The essential oils' mixtures reduced hydrophobicity of Candida yeasts in the range of 8.2 to 45.1%, depending on combination and strain. The interaction indexes of essential oils used in combinations predominantly indicate their additive effect. The application of tea tree, thyme and clove essential oils, especially in combinations, decreases hydrophobicity of the tested Candida isolates with implications of a probable advantageous limitation of their ability to colonize the food production industry environment. PMID:26601324

  3. Terpenoids inhibit Candida albicans growth by affecting membrane integrity and arrest of cell cycle.

    PubMed

    Zore, Gajanan B; Thakre, Archana D; Jadhav, Sitaram; Karuppayil, S Mohan

    2011-10-15

    Anti-Candida potential of six terpenoids were evaluated in this study against various isolates of Candida albicans (n=39) and non-C. albicans (n=9) that are differentially susceptible to fluconazole. All the six terpenoids tested, showed excellent activity and were equally effective against isolates of Candida sps., tested in this study. Linalool and citral were the most effective ones, inhibiting all the isolates at ≤0.064% (v/v). Five among the six terpenoids tested were fungicidal. Time dependent kill curve assay showed that MFCs of linalool and eugenol were highly toxic to C. albicans, killing 99.9% inoculum within seven min of exposure, while that of citronellal, linalyl acetate and citral required 15min, 1h and 2h, respectively. FIC index values (Linalool - 0.140, benzyl benzoate - 0.156, eugenol - 0.265, citral - 0.281 and 0.312 for linalyl acetate and citronellal) and isobologram obtained by checker board assay showed that all the six terpenoids tested exhibit excellent synergistic activity with fluconazole against a fluconazole resistant strain of C. albicans. Terpenoids tested arrested C. albicans cells at different phases of the cell cycle i.e. linalool and LA at G1, citral and citronellal at S phase and benzyl benzoate at G2-M phase and induced apoptosis. Linalool, citral, citronellal and benzyl benzoate caused more than 50% inhibition of germ tube induction at 0.008%, while eugenol and LA required 0.032 and 0.016% (v/v) concentrations, respectively. MICs of all the terpenoids for the C. albicans growth were non toxic to HeLa cells. Terpenoids tested exhibited excellent activity against C. albicans yeast and hyphal form growth at the concentrations that are non toxic to HeLa cells. Terpenoids tested in this study may find use in antifungal chemotherapy, not only as antifungal agents but also as synergistic agents along with conventional drugs like fluconazole.

  4. Direct identification and recognition of yeast species from clinical material by using albicans ID and CHROMagar Candida plates.

    PubMed Central

    Baumgartner, C; Freydiere, A M; Gille, Y

    1996-01-01

    Two chromogenic media, Albicans ID and CHROMagar Candida agar plates, were compared with a reference medium, Sabouraud-chloramphenicol agar, and standard methods for the identification of yeast species. This study involved 951 clinical specimens. The detection rates for the two chromogenic media for polymicrobial specimens were 20% higher than that for the Sabouraud-chloramphenicol agar plates. The rates of identification of Candida albicans for Albicans ID and CHROMagar Candida agar plates were, respectively, 37.0 and 6.0% after 24 h of incubation and 93.6 and 92.2% after 72 h of incubation, with specificities of 99.8 and 100%. Furthermore, CHROMagar Candida plates identified 13 of 14 Candida tropicalis and 9 of 12 Candida krusei strains after 48 h of incubation. PMID:8789038

  5. DNA content, kinetic complexity, and the ploidy question in Candida albicans.

    PubMed Central

    Riggsby, W S; Torres-Bauza, L J; Wills, J W; Townes, T M

    1982-01-01

    Candida albicans is a dimorphic fungus that is pathogenic for humans. No sexual cycle has been reported for this fungus, and earlier reports have differed on whether typical strains of C. albicans are haploid or diploid. Previous estimates of the DNA content of C. albicans varied by one order of magnitude. We used three independent methods to measure the kinetic complexity of the single-copy DNA from a typical strain of C. albicans (strain H317) to determine the DNA content per haploid genote; we obtained values of 15 and 20 fg per cell by using S1 nuclease and hydroxyapatite assays, respectively. Optical assays for DNA reassociation kinetics, although not definitive in themselves, yielded values in this range. Chemical measurements of the DNA content of several typical strains, including strain H317, yielded values clustered about a mean of 37 fg per cell. We concluded that these strains are diploid. PMID:6765567

  6. Increase of mouse resistance to Candida albicans infection by thymosin alpha 1.

    PubMed Central

    Bistoni, F; Marconi, P; Frati, L; Bonmassar, E; Garaci, E

    1982-01-01

    Studies were carried out to assess the ability of thymosin alpha 1 to prolong the survival of mice challenged with Candida albicans. Two- to four-month-old mice were treated with graded doses of thymosin alpha 1 before, after, or before and after intravenous challenge with C. albicans. Significant resistance ot lethal infection was afforded by 100 micrograms of thymosin alpha 1 per kg given before or before and after challenge, whereas no protection was found in mice treated with thymosin alpha 1 administered at any dose level after inoculation. Pretreatment with thymosin alpha 1 also prevented the increased susceptibility to C. albicans infection of mice pretreated with cyclophosphamide on day -6. The results showed that thymosin alpha 1 was capable of protecting untreated or cyclophosphamide-pretreated mice from C. albicans infection at an optimal dose and schedule of administration. PMID:7085074

  7. Additive potential of ginger starch on antifungal potency of honey against Candida albicans

    PubMed Central

    Moussa, Ahmed; Noureddine, Djebli; SM, Hammoudi; Saad, Aissat; Bourabeh, Akila; Houari, Hemida

    2012-01-01

    Objective To evaluate the additive action of ginger starch on the antifungal activity of honey against Candida albicans (C. albicans). Methods C. albicans was used to determine the minimum inhibitory concentration (MIC) of four varieties of Algerian honey. Lower concentrations of honey than the MIC were incubated with a set of concentrations of starch and then added to media to determine the minimum additive inhibitory concentration (MAIC). Results The MIC for the four varieties of honey without starch against C. albicans ranged between 38% and 42% (v/v). When starch was incubated with honey and then added to media, a MIC drop was noticed with each variety. MAIC of the four varieties ranged between 32% honey (v/v) with 4% starch and 36% honey (v/v) with 2% starch. Conclusions The use of ginger starch allows honey benefit and will constitute an alternative way against the resistance to antifungal agents. PMID:23569909

  8. Synthesis, antimicrobial evaluation and theoretical prediction of NMR chemical shifts of thiazole and selenazole derivatives with high antifungal activity against Candida spp.

    NASA Astrophysics Data System (ADS)

    Łączkowski, Krzysztof Z.; Motylewska, Katarzyna; Baranowska-Łączkowska, Angelika; Biernasiuk, Anna; Misiura, Konrad; Malm, Anna; Fernández, Berta

    2016-03-01

    Synthesis and investigation of antimicrobial activities of novel thiazoles and selenazoles is presented. Their structures were determined using NMR, FAB(+)-MS, HRMS and elemental analyses. To support the experiment, theoretical calculations of the 1H NMR shifts were carried out for representative systems within the DFT B3LYP/6-311++G** approximation which additionally confirmed the structure of investigated compounds. Among the derivatives, compounds 4b, 4h, 4j and 4l had very strong activity against reference strains of Candida albicans ATCC and Candida parapsilosis ATCC 22019 with MIC = 0.49-7.81 μg/ml. In the case of compounds 4b, 4c, 4h - 4j and 4l, the activity was very strong against of Candida spp. isolated from clinical materials, i.e. C. albicans, Candida krusei, Candida inconspicua, Candida famata, Candida lusitaniae, Candida sake, C. parapsilosis and Candida dubliniensis with MIC = 0.24-15.62 μg/ml. The activity of several of these was similar to the activity of commonly used antifungal agent fluconazole. Additionally, compounds 4m - 4s were found to be active against Gram-positive bacteria, both pathogenic staphylococci Staphylococcus aureus ATCC with MIC = 31.25-125 μg/ml and opportunistic bacteria, such as Staphylococcus epidermidis ATCC 12228 and Micrococcus luteus ATCC 10240 with MIC = 7.81-31.25 μg/ml.

  9. Synthesis, antimicrobial evaluation and theoretical prediction of NMR chemical shifts of thiazole and selenazole derivatives with high antifungal activity against Candida spp.

    NASA Astrophysics Data System (ADS)

    Łączkowski, Krzysztof Z.; Motylewska, Katarzyna; Baranowska-Łączkowska, Angelika; Biernasiuk, Anna; Misiura, Konrad; Malm, Anna; Fernández, Berta

    2016-03-01

    Synthesis and investigation of antimicrobial activities of novel thiazoles and selenazoles is presented. Their structures were determined using NMR, FAB(+)-MS, HRMS and elemental analyses. To support the experiment, theoretical calculations of the 1H NMR shifts were carried out for representative systems within the DFT B3LYP/6-311++G** approximation which additionally confirmed the structure of investigated compounds. Among the derivatives, compounds 4b, 4h, 4j and 4l had very strong activity against reference strains of Candida albicans ATCC and Candida parapsilosis ATCC 22019 with MIC = 0.49-7.81 μg/ml. In the case of compounds 4b, 4c, 4h - 4j and 4l, the activity was very strong against of Candida spp. isolated from clinical materials, i.e. C. albicans, Candida krusei, Candida inconspicua, Candida famata, Candida lusitaniae, Candida sake, C. parapsilosis and Candida dubliniensis with MIC = 0.24-15.62 μg/ml. The activity of several of these was similar to the activity of commonly used antifungal agent fluconazole. Additionally, compounds 4m - 4s were found to be active against Gram-positive bacteria, both pathogenic staphylococci Staphylococcus aureus ATCC with MIC = 31.25-125 μg/ml and opportunistic bacteria, such as Staphylococcus epidermidis ATCC 12228 and Micrococcus luteus ATCC 10240 with MIC = 7.81-31.25 μg/ml.

  10. Potent antifungal activity of extracts and pure compound isolated from pomegranate peels and synergism with fluconazole against Candida albicans.

    PubMed

    Endo, Eliana Harue; Cortez, Diógenes Aparício Garcia; Ueda-Nakamura, Tânia; Nakamura, Celso Vataru; Dias Filho, Benedito Prado

    2010-09-01

    Activity-guided repeated fractionation of crude hydro alcoholic extract prepared from the fruit peel of Punica granatum on a silica-gel column yielded a compound that exhibited strong antifungal activity against Candida spp. Based on spectral analyses, the compound was identified as punicalagin. Punicalagin showed strong activity against Candida albicans and Candida parapsilosis, with MICs of 3.9 and 1.9 microg/ml, respectively. The combination of punicalagin and fluconazole showed a synergistic interaction. MIC for fluconazole decreased twofold when combined with the extract. The FIC index was 0.25. The synergism observed in disk-diffusion and checkerboard assays was confirmed in time-kill curves. The effect of punicalagin on the morphology and ultrastructure in treated yeast cells was examined by scanning and transmission electron microscopy. An irregular budding pattern and pseudohyphae were seen in treated yeasts. By transmission electron microscopy, treated cells showed a thickened cell wall, changes in the space between cell wall and the plasma membrane, vacuoles, and a reduction in cytoplasmic content. Since the punicalagin concentration effective in vitro is achievable in vivo, the combination of this agent with fluconazole represents an attractive prospect for the development of new management strategies for candidiasis, and should be investigated further in in vivo models. PMID:20541606

  11. [In vitro biofilm formation and relationship with antifungal resistance of Candida spp. isolated from vaginal and intrauterine device string samples of women with vaginal complaints].

    PubMed

    Calışkan, Seyda; Keçeli Özcan, Sema; Cınar, Selvi; Corakçı, Aydın; Calışkan, Eray

    2011-10-01

    Intrauterin device (IUD) application is a widely used effective, safe and economic method for family planning. However IUD use may cause certain changes in vaginal ecosystem and may disturb microflora leading to increased colonization of various opportunistic pathogen microorganisms. The aims of this study were (i) to detect the biofilm production characteristics of Candida spp. isolated from vaginal and IUD string samples of women with IUDs, and (ii) to investigate the relationship between biofilm production and antifungal resistance. A total of 250 women (mean age: 34.4 ± 7.6 years) admitted to gynecology outpatient clinics with vaginal symptoms (discharge and itching) were included in the study. The patients have been implanted CuT380a type IUDs for a mean duration of 59.8 ± 42.4 months. Without removing IUD, string samples were obtained by cutting and simultaneous vaginal swab samples were also collected. Isolated Candida spp. were identified by conventional methods and API 20C AUX (BioMerieux, Fransa) system. Minimal inhibitory concentrations (MIC) of fluconazole, itraconazole and amphotericin B were determined by broth microdilution method according to the CLSI guidelines. Biofilm formation was evaluated by crystal violet staining and XTT-reduction assays, and the isolates which yielded positive results in both of the methods were accepted as biofilm-producers. In the study, Candida spp. were isolated from 33.2% (83/250) of the vaginal and 34% (85/250) of the IUD string samples, C.albicans being the most frequently detected species (54 and 66 strains for the samples, respectively). The total in vitro biofilm formation rate was 25% (21/83) for vaginal isolates and 44.7% (38/85) for IUD string isolates. Biofilm formation rate of vaginal C.albicans isolates was significantly lower than vaginal non-albicans Candida spp. (14.8% and 44.8%, respectively; p= 0.003). Biofilm formation rate of C.albicans strains isolated from vaginal and IUD string samples were found

  12. Effect of Candida albicans on Intestinal Ischemia-reperfusion Injury in Rats

    PubMed Central

    Yan, Lei; Wu, Chun-Rong; Wang, Chen; Yang, Chun-Hui; Tong, Guang-Zhi; Tang, Jian-Guo

    2016-01-01

    Background: Inflammation is supposed to play a key role in the pathophysiological processes of intestinal ischemia-reperfusion injury (IIRI), and Candida albicans in human gut commonly elevates inflammatory cytokines in intestinal mucosa. This study aimed to explore the effect of C. albicans on IIRI. Methods: Fifty female Wistar rats were divided into five groups according to the status of C. albicans infection and IIRI operation: group blank and sham; group blank and IIRI; group cefoperazone plus IIRI; group C. albicans plus cefoperazone and IIRI (CCI); and group C. albicans plus cefoperazone and sham. The levels of inflammatory factors tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and diamine oxidase (DAO) measured by enzyme-linked immunosorbent assay were used to evaluate the inflammation reactivity as well as the integrity of small intestine. Histological scores were used to assess the mucosal damage, and the C. albicans blood translocation was detected to judge the permeability of intestinal mucosal barrier. Results: The levels of inflammatory factors TNF-α, IL-6, and IL-1β in serum and intestine were higher in rats undergone both C. albicans infection and IIRI operation compared with rats in other groups. The levels of DAO (serum: 44.13 ± 4.30 pg/ml, intestine: 346.21 ± 37.03 pg/g) and Chiu scores (3.41 ± 1.09) which reflected intestinal mucosal disruption were highest in group CCI after the operation. The number of C. albicans translocated into blood was most in group CCI ([33.80 ± 6.60] ×102 colony forming unit (CFU)/ml). Conclusion: Intestinal C. albicans infection worsened the IIRI-induced disruption of intestinal mucosal barrier and facilitated the subsequent C. albicans translocation and dissemination. PMID:27411459

  13. Effect of UV irradiation on lethal infection of mice with Candida albicans.

    PubMed

    Denkins, Y M; Kripke, M L

    1993-02-01

    Exposure of mice to UV radiation inhibits the induction and elicitation of the delayed-type hypersensitivity (DTH) response to Candida albicans. To determine whether UV irradiation also affects the pathogenesis of systemic C. albicans infection, C3H mice were exposed to a single dose of 48 kJ/m2 UV-B radiation from FS40 sunlamps 5 days before or 5 days after sensitization with formalin-fixed C. albicans and challenged intravenously (i.v.) with a lethal dose of viable fungi 6 days after sensitization (11 or 1 days after UV irradiation). Exposing unsensitized mice to UV radiation 11 days before lethal challenge had no effect on survival, but the survival time of mice exposed to UV radiation 1 day before challenge was reduced by more than 50%. In the latter group, decreased survival time correlated with persistence of C. albicans in the brain and progressive growth of C. albicans in the kidneys. Sensitization of unirradiated mice with formalin-fixed C. albicans extended their survival time following lethal i.v. challenge with viable C. albicans. Exposing the mice to UV radiation 5 days before sensitization did not abrogate this beneficial effect of sensitization on survival, even though it significantly reduced the DTH response. Thus, immunity to systemic infection did not depend on the ability of the mice to exhibit a DTH response to C. albicans. The beneficial effect of sensitization on survival after lethal infection was abrogated, however, in mice exposed to UV radiation 1 day before lethal challenge with C. albicans. Furthermore, these mice were unable to contain the progressive growth of C. albicans in the kidneys, in contrast to sensitized, unirradiated mice. PMID:8451288

  14. Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder

    PubMed Central

    Severance, Emily G; Gressitt, Kristin L; Stallings, Catherine R; Katsafanas, Emily; Schweinfurth, Lucy A; Savage, Christina L; Adamos, Maria B; Sweeney, Kevin M; Origoni, Andrea E; Khushalani, Sunil; Leweke, F Markus; Dickerson, Faith B; Yolken, Robert H

    2016-01-01

    Immune aberrations in schizophrenia and bipolar disorder have led to the hypotheses that infectious agents or corresponding immune responses might contribute to psychiatric etiopathogeneses. We investigated case–control differences in exposure to the opportunistic fungal pathogen, Candida albicans, and examined associations with cognition, medication, lifestyle, and somatic conditions. We quantified C. albicans IgG antibodies in two cohorts totaling 947 individuals and evaluated odds ratios (OR) of exposure with psychiatric disorder using multivariate regressions. The case–control cohort included 261 with schizophrenia, 270 with bipolar disorder, and 277 non-psychiatric controls; the second included 139 with first-episode schizophrenia, 78 of whom were antipsychotic naive. No differences in C. albicans exposures were found until diagnostic groups were stratified by sex. In males, C. albicans seropositivity conferred increased odds for a schizophrenia diagnosis (OR 2.04–9.53, P⩽0.0001). In females, C. albicans seropositivity conferred increased odds for lower cognitive scores on Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in schizophrenia (OR 1.12, P⩽0.004), with significant decreases on memory modules for both disorders (P⩽0.0007–0.03). C. albicans IgG levels were not impacted by antipsychotic medications. Gastrointestinal (GI) disturbances were associated with elevated C. albicans in males with schizophrenia and females with bipolar disorder (P⩽0.009–0.02). C. albicans exposure was associated with homelessness in bipolar males (P⩽0.0015). In conclusion, sex-specific C. albicans immune responses were evident in psychiatric disorder subsets. Inquiry regarding C. albicans infection or symptoms may expedite amelioration of this treatable comorbid condition. Yeast exposure as a risk factor for schizophrenia and its associated cognitive and GI effects require further investigation including the possible contribution of

  15. Streptococcus mutans Can Modulate Biofilm Formation and Attenuate the Virulence of Candida albicans.

    PubMed

    Barbosa, Júnia Oliveira; Rossoni, Rodnei Dennis; Vilela, Simone Furgeri Godinho; de Alvarenga, Janaína Araújo; Velloso, Marisol dos Santos; Prata, Márcia Cristina de Azevedo; Jorge, Antonio Olavo Cardoso; Junqueira, Juliana Campos

    2016-01-01

    Streptococcus mutans and Candida albicans are found together in the oral biofilms on dental surfaces, but little is known about the ecological interactions between these species. Here, we studied the effects of S. mutans UA159 on the growth and pathogencity of C. albicans. Initially, the effects of S. mutans on the biofilm formation and morphogenesis of C. albicans were tested in vitro. Next, we investigate the influence of S. mutans on pathogenicity of C. albicans using in vivo host models, in which the experimental candidiasis was induced in G. mellonella larvae and analyzed by survival curves, C. albicans count in hemolymph, and quantification of hyphae in the host tissues. In all the tests, we evaluated the direct effects of S. mutans cells, as well as the indirect effects of the subproducts secreted by this microorganism using a bacterial culture filtrate. The in vitro analysis showed that S. mutans cells favored biofilm formation by C. albicans. However, a reduction in biofilm viable cells and inhibition of hyphal growth was observed when C. albicans was in contact with the S. mutans culture filtrate. In the in vivo study, injection of S. mutans cells or S. mutans culture filtrate into G. mellonella larvae infected with C. albicans increased the survival of these animals. Furthermore, a reduction in hyphal formation was observed in larval tissues when C. albicans was associated with S. mutans culture filtrate. These findings suggest that S. mutans can secrete subproducts capable to inhibit the biofilm formation, morphogenesis and pathogenicity of C. albicans, attenuating the experimental candidiasis in G. mellonella model.

  16. Streptococcus mutans Can Modulate Biofilm Formation and Attenuate the Virulence of Candida albicans

    PubMed Central

    Barbosa, Júnia Oliveira; Rossoni, Rodnei Dennis; Vilela, Simone Furgeri Godinho; de Alvarenga, Janaína Araújo; Velloso, Marisol dos Santos; Prata, Márcia Cristina de Azevedo; Jorge, Antonio Olavo Cardoso; Junqueira, Juliana Campos

    2016-01-01

    Streptococcus mutans and Candida albicans are found together in the oral biofilms on dental surfaces, but little is known about the ecological interactions between these species. Here, we studied the effects of S. mutans UA159 on the growth and pathogencity of C. albicans. Initially, the effects of S. mutans on the biofilm formation and morphogenesis of C. albicans were tested in vitro. Next, we investigate the influence of S. mutans on pathogenicity of C. albicans using in vivo host models, in which the experimental candidiasis was induced in G. mellonella larvae and analyzed by survival curves, C. albicans count in hemolymph, and quantification of hyphae in the host tissues. In all the tests, we evaluated the direct effects of S. mutans cells, as well as the indirect effects of the subproducts secreted by this microorganism using a bacterial culture filtrate. The in vitro analysis showed that S. mutans cells favored biofilm formation by C. albicans. However, a reduction in biofilm viable cells and inhibition of hyphal growth was observed when C. albicans was in contact with the S. mutans culture filtrate. In the in vivo study, injection of S. mutans cells or S. mutans culture filtrate into G. mellonella larvae infected with C. albicans increased the survival of these animals. Furthermore, a reduction in hyphal formation was observed in larval tissues when C. albicans was associated with S. mutans culture filtrate. These findings suggest that S. mutans can secrete subproducts capable to inhibit the biofilm formation, morphogenesis and pathogenicity of C. albicans, attenuating the experimental candidiasis in G. mellonella model. PMID:26934196

  17. Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder.

    PubMed

    Severance, Emily G; Gressitt, Kristin L; Stallings, Catherine R; Katsafanas, Emily; Schweinfurth, Lucy A; Savage, Christina L; Adamos, Maria B; Sweeney, Kevin M; Origoni, Andrea E; Khushalani, Sunil; Leweke, F Markus; Dickerson, Faith B; Yolken, Robert H

    2016-01-01

    Immune aberrations in schizophrenia and bipolar disorder have led to the hypotheses that infectious agents or corresponding immune responses might contribute to psychiatric etiopathogeneses. We investigated case-control differences in exposure to the opportunistic fungal pathogen, Candida albicans, and examined associations with cognition, medication, lifestyle, and somatic conditions. We quantified C. albicans IgG antibodies in two cohorts totaling 947 individuals and evaluated odds ratios (OR) of exposure with psychiatric disorder using multivariate regressions. The case-control cohort included 261 with schizophrenia, 270 with bipolar disorder, and 277 non-psychiatric controls; the second included 139 with first-episode schizophrenia, 78 of whom were antipsychotic naive. No differences in C. albicans exposures were found until diagnostic groups were stratified by sex. In males, C. albicans seropositivity conferred increased odds for a schizophrenia diagnosis (OR 2.04-9.53, P⩽0.0001). In females, C. albicans seropositivity conferred increased odds for lower cognitive scores on Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in schizophrenia (OR 1.12, P⩽0.004), with significant decreases on memory modules for both disorders (P⩽0.0007-0.03). C. albicans IgG levels were not impacted by antipsychotic medications. Gastrointestinal (GI) disturbances were associated with elevated C. albicans in males with schizophrenia and females with bipolar disorder (P⩽0.009-0.02). C. albicans exposure was associated with homelessness in bipolar males (P⩽0.0015). In conclusion, sex-specific C. albicans immune responses were evident in psychiatric disorder subsets. Inquiry regarding C. albicans infection or symptoms may expedite amelioration of this treatable comorbid condition. Yeast exposure as a risk factor for schizophrenia and its associated cognitive and GI effects require further investigation including the possible contribution of gut

  18. Treatment with probiotics in experimental oral colonization by Candida albicans in murine model (DBA/2).

    PubMed

    Matsubara, V H; Silva, E G; Paula, C R; Ishikawa, K H; Nakamae, A E M

    2012-04-01

    The aim of this study is to evaluate the oral colonization by Candida albicans in experimental murine immunosuppressed DBA/2 and treatment with probiotic bacteria. To achieve these objectives, 152 DBA/2-immunosuppressed mice were orally inoculated with a suspension of C. albicans containing 10(8) viable yeast cells, the animals were treated with nystatin or with the probiotics (Lactobacillus acidophilus and Lactobacillus rhamnosus). Evaluations were performed by Candida count from oral mucosa swabbing. The oral mucosa colonization by C. albicans started at day 1 after inoculation, remained maximal from day 3 until day 7, and then decreased significantly. Probiotics reduced the C. albicans colonization significantly on the oral mucosa in comparison with the untreated animal group. In the group treated with L. rhamnosus, the reduction in yeast colonization was significantly higher compared with that of the group receiving nystatin. Immunosuppressed animal model DBA/2 is a relevant model for experimental Candida oral colonization, and the treatment with probiotics in this model may be an effective alternative to prevent it.

  19. O-mannosylation in Candida albicans enables development of interkingdom biofilm communities.

    PubMed

    Dutton, Lindsay C; Nobbs, Angela H; Jepson, Katy; Jepson, Mark A; Vickerman, M Margaret; Aqeel Alawfi, Sami; Munro, Carol A; Lamont, Richard J; Jenkinson, Howard F

    2014-04-15

    Candida albicans is a fungus that colonizes oral cavity surfaces, the gut, and the genital tract. Streptococcus gordonii is a ubiquitous oral bacterium that has been shown to form biofilm communities with C. albicans. Formation of dual-species S. gordonii-C. albicans biofilm communities involves interaction of the S. gordonii SspB protein with the Als3 protein on the hyphal filament surface of C. albicans. Mannoproteins comprise a major component of the C. albicans cell wall, and in this study we sought to determine if mannosylation in cell wall biogenesis of C. albicans was necessary for hyphal adhesin functions associated with interkingdom biofilm development. A C. albicans mnt1Δ mnt2Δ mutant, with deleted α-1,2-mannosyltransferase genes and thus defective in O-mannosylation, was abrogated in biofilm formation under various growth conditions and produced hyphal filaments that were not recognized by S. gordonii. Cell wall proteomes of hypha-forming mnt1Δ mnt2Δ mutant cells showed growth medium-dependent alterations, compared to findings for the wild type, in a range of protein components, including Als1, Als3, Rbt1, Scw1, and Sap9. Hyphal filaments formed by mnt1Δ mnt2Δ mutant cells, unlike wild-type hyphae, did not interact with C. albicans Als3 or Hwp1 partner cell wall proteins or with S. gordonii SspB partner adhesin, suggesting defective functionality of adhesins on the mnt1Δ mnt2Δ mutant. These observations imply that early stage O-mannosylation is critical for activation of hyphal adhesin functions required for biofilm formation, recognition by bacteria such as S. gordonii, and microbial community development. IMPORTANCE In the human mouth, microorganisms form communities known as biofilms that adhere to the surfaces present. Candida albicans is a fungus that is often found within these biofilms. We have focused on the mechanisms by which C. albicans becomes incorporated into communities containing bacteria, such as Streptococcus. We find that

  20. Presence of extracellular DNA in the Candida albicans biofilm matrix and its contribution to biofilms.

    PubMed

    Martins, Margarida; Uppuluri, Priya; Thomas, Derek P; Cleary, Ian A; Henriques, Mariana; Lopez-Ribot, José L; Oliveira, Rosário

    2010-05-01

    DNA has been described as a structural component of the extracellular matrix (ECM) in bacterial biofilms. In Candida albicans, there is a scarce knowledge concerning the contribution of extracellular DNA (eDNA) to biofilm matrix and overall structure. This work examined the presence and quantified the amount of eDNA in C. albicans biofilm ECM and the effect of DNase treatment and the addition of exogenous DNA on C. albicans biofilm development as indicators of a role for eDNA in biofilm development. We were able to detect the accumulation of eDNA in biofilm ECM extracted from C. albicans biofilms formed under conditions of flow, although the quantity of eDNA detected differed according to growth conditions, in particular with regards to the medium used to grow the biofilms. Experiments with C. albicans biofilms formed statically using a microtiter plate model indicated that the addition of exogenous DNA (>160 ng/ml) increases biofilm biomass and, conversely, DNase treatment (>0.03 mg/ml) decreases biofilm biomass at later time points of biofilm development. We present evidence for the role of eDNA in C. albicans biofilm structure and formation, consistent with eDNA being a key element of the ECM in mature C. albicans biofilms and playing a predominant role in biofilm structural integrity and maintenance.

  1. Candida albicans-induced agglutinin and immunoglobulin E responses in mice.

    PubMed Central

    Winterrowd, G E; Cutler, J E

    1983-01-01

    Mice varied in their ability to make detectable antibody responses to cell surface determinants of Candida albicans depending upon the antigen preparation and the immunization schedule used. Immunoglobulin M (IgM) appeared to be the major class of antibody responsible for the C. albicans-agglutinating activity of the immune sera. Various inbred strains of mice injected with a ribosomal fraction from C. albicans produced a low titer (average, 4 to 8) of yeast cell agglutinins and a higher titer (64 to 512) of IgE antibodies detected by passive cutaneous anaphylaxis (PCA) in rats. The two kinds of antibodies appeared to be specific for different antigens because the agglutinin, but not IgE, could be removed by absorbing the serum with a polysaccharide from the cell wall of C. albicans, but the polysaccharide did not provoke the PCA reaction. C. albicans-specific IgE antibodies showed cross-reactivity (PCA) with ribosomal antigens from a strain of C. albicans and C. tropicalis, but PCA reactions could not be elicited with similar antigen preparations from other yeast species. IgE responses were also detected in over 20% of the mice infected intravenously or intraperitoneally with live C. albicans. PMID:6190755

  2. Candida albicans Amphotericin B-Tolerant Persister Formation is Closely Related to Surface Adhesion.

    PubMed

    Sun, Jing; Li, Zhigang; Chu, Haoyue; Guo, Jing; Jiang, Guangshui; Qi, Qingguo

    2016-02-01

    Candida albicans persisters have so far been observed only in biofilm environment; the biofilm element(s) that trigger(s) persister formation are still unknown. In this study, we tried to further elucidate the possible relationship between C. albicans persisters and the early phases of biofilm formation, especially the surface adhesion phase. Three C. albicans strains were surveyed for the formation of persisters. We tested C. albicans persister formation dynamically at different time points during the process of adhesion and biofilm formation. The number of persister cells was determined based on an assessment of cell viability after amphotericin B treatment and colony-forming unit assay. None of the planktonic cultures contained persisters. Immediately following adhesion of C. albicans cells to the surface, persister cells emerged and the proportion of persisters reached a peak of 0.2-0.69 % in approximately 2-h biofilm. As the biofilm matured, the proportion of persisters decreased and was only 0.01-0.02 % by 24 h, while the number of persisters remained stable with no significant change. Persisters were not detected in the absence of an attachment surface which was pre-coated. Persisters were also absent in biofilms that were scraped to disrupt surface adhesion prior to amphotericin B treatment. These results indicate that C. albicans antifungal-tolerant persisters are produced mainly in surface adhesion phase and surface adhesion is required for the emergence and maintenance of C. albicans persisters.

  3. Essential Functional Modules for Pathogenic and Defensive Mechanisms in Candida albicans Infections

    PubMed Central

    Tsai, I-Chun; Lin, Che; Chuang, Yung-Jen

    2014-01-01

    The clinical and biological significance of the study of fungal pathogen Candida albicans (C. albicans) has markedly increased. However, the explicit pathogenic and invasive mechanisms of such host-pathogen interactions have not yet been fully elucidated. Therefore, the essential functional modules involved in C. albicans-zebrafish interactions were investigated in this study. Adopting a systems biology approach, the early-stage and late-stage protein-protein interaction (PPI) networks for both C. albicans and zebrafish were constructed. By comparing PPI networks at the early and late stages of the infection process, several critical functional modules were identified in both pathogenic and defensive mechanisms. Functional modules in C. albicans, like those involved in hyphal morphogenesis, ion and small molecule transport, protein secretion, and shifts in carbon utilization, were seen to play important roles in pathogen invasion and damage caused to host cells. Moreover, the functional modules in zebrafish, such as those involved in immune response, apoptosis mechanisms, ion transport, protein secretion, and hemostasis-related processes, were found to be significant as defensive mechanisms during C. albicans infection. The essential functional modules thus determined could provide insights into the molecular mechanisms of host-pathogen interactions during the infection process and thereby devise potential therapeutic strategies to treat C. albicans infection. PMID:24757665

  4. Adherence of Candida albicans to a cell surface polysaccharide receptor on Streptococcus gordonii.

    PubMed Central

    Holmes, A R; Gopal, P K; Jenkinson, H F

    1995-01-01

    Candida albicans ATCC 10261 and CA2 bound to cells of the oral bacteria Streptococcus gordonii, Streptococcus oralis, and Streptococcus sanguis when these bacteria were immobilized onto microtiter plate wells, but they did not bind to cells of Streptococcus mutans or Streptococcus salivarius. Cell wall polysaccharide was extracted with alkali from S. gordonii NCTC 7869, the streptococcal species to which C. albicans bound with highest affinity, and was effective in blocking the coaggregation of C. albicans and S. gordonii cells in the fluid phase. When fixed to microtiter plate wells, the S. gordonii polysaccharide was bound by all strains of C. albicans tested. The polysaccharide contained Rha, Glc, GalNAc, GlcNAc, and Gal and was related compositionally to previously characterized cell wall polysaccharides from strains of S. oralis and S. sanguis. The adherence of yeast cells to the immobilized polysaccharide was not inhibitable by a number of saccharides. Antiserum raised to the S. gordonii NCTC 7869 polysaccharide blocked adherence of C. albicans ATCC 10261 to the polysaccharide. The results identify a complex cell wall polysaccharide of S. gordonii as the coaggregation receptor for C. albicans. Adherent interactions of yeast cells with streptococci and other bacteria may be important for colonization of both hard and soft oral surfaces by C. albicans. PMID:7729891

  5. Antifungal activity of Rubus chingii extract combined with fluconazole against fluconazole-resistant Candida albicans.

    PubMed

    Han, Bing; Chen, Jia; Yu, Yi-qun; Cao, Yong-bing; Jiang, Yuan-ying

    2016-02-01

    This study aimed to investigate the antifungal activity of Rubus chingii extract in combination with fluconazole (FLC) against FLC-resistant Candida albicans 100 in vitro. A R. chingii extract and FLC-resistant C. albicans fungus suspension were prepared. The minimum inhibitory concentration and fractional inhibitory concentration index of R. chingii extract combined with FLC against C. albicans were determined, after which growth curves for C. albicans treated with R. chingii extract, FLC alone and a combination of these preparations were constructed. Additionally, the mechanisms of drug combination against C. albicans were explored by flow cytometry, gas chromatographic mass spectrometry and drug efflux pump function detection. R. chingii extract combined with FLC showed significant synergy. Flow cytometry suggested that C. albicans cells mainly arrest in G1 and S phases when they have been treated with the drug combination. The drug combination resulted in a marked decrease in the ergosterol content of the cell membrane. Additionally, efflux of Rhodamine 6G decreased with increasing concentrations of R. chingii extract. R. chingii extract combined with FLC has antifungal activity against FLC-resistant C. albicans. PMID:26891940

  6. Modulation of Candida albicans virulence by bacterial biofilms on titanium surfaces.

    PubMed

    Cavalcanti, Yuri Wanderley; Wilson, Melanie; Lewis, Michael; Del-Bel-Cury, Altair Antoninha; da Silva, Wander José; Williams, David W

    2016-01-01

    Whilst Candida albicans occurs in peri-implant biofilms, its role in peri-implantitis remains unclear. This study therefore examined the virulence of C. albicans in mixed-species biofilms on titanium surfaces. Biofilms of C. albicans (Ca), C. albicans with streptococci (Streptococcus sanguinis, S. mutans) (Ca-Ss-Sm) and those incorporating Porphyromonas gingivalis (Ca-Pg and Ca-Ss-Sm-Pg) were developed. Expression of C. albicans genes associated with adhesion (ALS1, ALS3, HWP1) and hydrolytic enzymes (SAP2, SAP4, SAP6, PLD1) was measured and hyphal production by C. albicans quantified. Compared with Ca biofilms, significant (p<0.05) up-regulation of ALS3, HWP1, SAP2 and SAP6, and hyphal production occurred in biofilms containing streptococci (Ca-Ss-Sm). In Ca-Pg biofilms, down-regulation of HWP1 and SAP4 expression, with reduced hyphal production occurred. Ca-Ss-Sm-Pg biofilms had increased hyphal proportions and up-regulation of ALS3, SAP2 and SAP6. In conclusion, C. albicans expressed virulence factors in biofilms that could contribute to peri-implantitis, but this was dependent on associated bacterial species.

  7. [The effects of an aroma candy on oral Candida albicans colony-forming units (CFU) and oral hygiene states in healthy elderly carrying Candida albicans].

    PubMed

    Suzuki, Motofumi; Hayama, Kazumi; Takahashi, Miki; Ezawa, Kunio; Yamazaki, Masatoshi; Matsukawa, Taiji; Kishi, Akinobu; Satou, Nobuya; Abe, Shigeru

    2015-01-01

    In a preceding paper, we showed that aroma candy containing oligonol, capric acid, and cinnamon (cassia) powder had potent inhibitory activity against mycelial growth of Candida albicans in vitro and protective activity against murine oral candidiasis. In order to assess the effects of this candy (the test candy) on oral C. albicans colony-forming units (CFU) and oral hygiene states, a placebo-controlled double-blind crossover comparative study was performed. Twenty subjects were divided into two groups. One group ingested the test candy in the first 7 days followed by 2 weeks washing-off period, then ingested the placebo candy (control candy) for 7 days. The other group was vice versa. C. albicans CFU in all oral rinse samples from the subjects before and after 7 days ingestion of candy was measured. The degree of oral malodor in all subjects was monitored using a portable measuring instrument. The results showed no statistically significant difference between test-candy group and placebo group for C. albicans CFU. However, C. albicans CFU in test-candy group with>4,000 CFUs was significantly decreased after 7 days ingestion of test-candy (p<0.05). Scores of oral malodor in the test-candy group was significantly decreased after 7 days ingestion of test-candy (p<0.05). A questionnaire survey of oral hygiene states indicated that in the test-candy group, oral malodor, glutinous feeling, and refreshing feeling significantly improved in comparison with control-candy group (p<0.05). Our study suggests that the aroma candy is effective in oral health care of elderly carrying C. albicans.

  8. Prevalence and antifungal susceptibility of Candida albicans and its related species Candida dubliniensis and Candida africana isolated from vulvovaginal samples in a hospital of Argentina.

    PubMed

    Theill, Laura; Dudiuk, Catiana; Morano, Susana; Gamarra, Soledad; Nardin, María Elena; Méndez, Emilce; Garcia-Effron, Guillermo

    2016-01-01

    Candida africana taxonomical status is controversial. It was proposed as a separate species within the Candida albicans species complex; however, phylogenetic analyses suggested that it is an unusual variety of C. albicans. The prevalence of C. albicans-related species (Candida dubliniensis and C. africana) as vulvovaginal pathogens is not known in Argentina. Moreover, data on antifungal susceptibility of isolates causing vulvovaginal candidiasis is scarce. The aims of this study were to establish the prevalence of C. dubliniensis and C. africana in vaginal samples and to evaluate the antifungal susceptibilities of vaginal C. albicans species complex strains. We used a molecular-based method coupled with a new pooled DNA extraction methodology to differentiate C. dubliniensis and C. africana in a collection of 287 strains originally identified as C. albicans isolated from an Argentinian hospital during 2013. Antifungal susceptibilities to fluconazole, clotrimazole, itraconazole, voriconazole, nystatin, amphotericin B and terbinafine were evaluated by using the CLSI M27-A3 and M27-S4 documents. Of the 287 isolates, 4 C. dubliniensis and one C. africana strains (1.39% and 0.35% prevalence, respectively) were identified. This is the first description of C. africana in Argentina and its identification was confirmed by sequencing the ITS2 region and the hwp1 gene. C. dubliniensis and C. africana strains showed very low MIC values for all the tested antifungals. Fluconazole-reduced-susceptibility and azole cross-resistance were observed in 3.55% and 1.41% of the C. albicans isolates, respectively. These results demonstrate that antifungal resistance is still a rare phenomenon in this kind of isolates.

  9. Prevalence and antifungal susceptibility of Candida albicans and its related species Candida dubliniensis and Candida africana isolated from vulvovaginal samples in a hospital of Argentina.

    PubMed

    Theill, Laura; Dudiuk, Catiana; Morano, Susana; Gamarra, Soledad; Nardin, María Elena; Méndez, Emilce; Garcia-Effron, Guillermo

    2016-01-01

    Candida africana taxonomical status is controversial. It was proposed as a separate species within the Candida albicans species complex; however, phylogenetic analyses suggested that it is an unusual variety of C. albicans. The prevalence of C. albicans-related species (Candida dubliniensis and C. africana) as vulvovaginal pathogens is not known in Argentina. Moreover, data on antifungal susceptibility of isolates causing vulvovaginal candidiasis is scarce. The aims of this study were to establish the prevalence of C. dubliniensis and C. africana in vaginal samples and to evaluate the antifungal susceptibilities of vaginal C. albicans species complex strains. We used a molecular-based method coupled with a new pooled DNA extraction methodology to differentiate C. dubliniensis and C. africana in a collection of 287 strains originally identified as C. albicans isolated from an Argentinian hospital during 2013. Antifungal susceptibilities to fluconazole, clotrimazole, itraconazole, voriconazole, nystatin, amphotericin B and terbinafine were evaluated by using the CLSI M27-A3 and M27-S4 documents. Of the 287 isolates, 4 C. dubliniensis and one C. africana strains (1.39% and 0.35% prevalence, respectively) were identified. This is the first description of C. africana in Argentina and its identification was confirmed by sequencing the ITS2 region and the hwp1 gene. C. dubliniensis and C. africana strains showed very low MIC values for all the tested antifungals. Fluconazole-reduced-susceptibility and azole cross-resistance were observed in 3.55% and 1.41% of the C. albicans isolates, respectively. These results demonstrate that antifungal resistance is still a rare phenomenon in this kind of isolates. PMID:26922471

  10. Beyond the wall: Candida albicans secret(e)s to survive.

    PubMed

    Sorgo, Alice G; Heilmann, Clemens J; Brul, Stanley; de Koster, Chris G; Klis, Frans M

    2013-01-01

    The opportunistic fungal pathogen Candida albicans occupies various niches of the human body such as the skin and the mucosal surfaces of the gastrointestinal and urogenital tracts. It can also enter the blood stream and cause deadly, systemic infections, especially in immunocompromised patients, but also in immunocompetent individuals through inserted medical devices. To survive in these diverse host environments, C. albicans has developed specialized virulence attributes and rapidly adapts itself to local growth conditions and defense mechanisms. Candida albicans secretes a considerable number of proteins that are involved in biofilm formation, tissue invasion, immune evasion, and wall maintenance, as well as acquisition of nutrients including metal ions. The secretome of C. albicans is predicted to comprise 225 proteins. On a proteomic level, however, analysis of the secretome of C. albicans is incomplete as many secreted proteins are only produced under certain conditions. Interestingly, glycosylphosphatidylinositol proteins and known cytoplasmic proteins are also consistently detected in the growth medium. Importantly, a core set of seven wall polysaccharide-processing enzymes seems to be consistently present, including the diagnostic marker Mp65. Overall, we discuss the importance of the secretome for virulence and suggest potential targets for better and faster diagnostic methods.

  11. The Extracellular Matrix of Candida albicans Biofilms Impairs Formation of Neutrophil Extracellular Traps

    PubMed Central

    Cabezas-Olcoz, Jonathan; Wang, Steven X.; Huttenlocher, Anna; Ansari, Hamayail; Nett, Jeniel E.

    2016-01-01

    Neutrophils release extracellular traps (NETs) in response to planktonic C. albicans. These complexes composed of DNA, histones, and proteins inhibit Candida growth and dissemination. Considering the resilience of Candida biofilms to host defenses, we examined the neutrophil response to C. albicans during biofilm growth. In contrast to planktonic C. albicans, biofilms triggered negligible release of NETs. Time lapse imaging confirmed the impairment in NET release and revealed neutrophils adhering to hyphae and migrating on the biofilm. NET inhibition depended on an intact extracellular biofilm matrix as physical or genetic disruption of this component resulted in NET release. Biofilm inhibition of NETosis could not be overcome by protein kinase C activation via phorbol myristate acetate (PMA) and was associated with suppression of neutrophil reactive oxygen species (ROS) production. The degree of impaired NET release correlated with resistance to neutrophil attack. The clinical relevance of the role for extracellular matrix in diminishing NET production was corroborated in vivo using a rat catheter model. The C. albicans pmr1Δ/Δ, defective in production of matrix mannan, appeared to elicit a greater abundance of NETs by scanning electron microscopy imaging, which correlated with a decreased fungal burden. Together, these findings show that C. albicans biofilms impair neutrophil response through an inhibitory pathway induced by the extracellular matrix. PMID:27622514

  12. The Extracellular Matrix of Candida albicans Biofilms Impairs Formation of Neutrophil Extracellular Traps.

    PubMed

    Johnson, Chad J; Cabezas-Olcoz, Jonathan; Kernien, John F; Wang, Steven X; Beebe, David J; Huttenlocher, Anna; Ansari, Hamayail; Nett, Jeniel E

    2016-09-01

    Neutrophils release extracellular traps (NETs) in response to planktonic C. albicans. These complexes composed of DNA, histones, and proteins inhibit Candida growth and dissemination. Considering the resilience of Candida biofilms to host defenses, we examined the neutrophil response to C. albicans during biofilm growth. In contrast to planktonic C. albicans, biofilms triggered negligible release of NETs. Time lapse imaging confirmed the impairment in NET release and revealed neutrophils adhering to hyphae and migrating on the biofilm. NET inhibition depended on an intact extracellular biofilm matrix as physical or genetic disruption of this component resulted in NET release. Biofilm inhibition of NETosis could not be overcome by protein kinase C activation via phorbol myristate acetate (PMA) and was associated with suppression of neutrophil reactive oxygen species (ROS) production. The degree of impaired NET release correlated with resistance to neutrophil attack. The clinical relevance of the role for extracellular matrix in diminishing NET production was corroborated in vivo using a rat catheter model. The C. albicans pmr1Δ/Δ, defective in production of matrix mannan, appeared to elicit a greater abundance of NETs by scanning electron microscopy imaging, which correlated with a decreased fungal burden. Together, these findings show that C. albicans biofilms impair neutrophil response through an inhibitory pathway induced by the extracellular matrix. PMID:27622514

  13. Beyond the wall: Candida albicans secret(e)s to survive.

    PubMed

    Sorgo, Alice G; Heilmann, Clemens J; Brul, Stanley; de Koster, Chris G; Klis, Frans M

    2013-01-01

    The opportunistic fungal pathogen Candida albicans occupies various niches of the human body such as the skin and the mucosal surfaces of the gastrointestinal and urogenital tracts. It can also enter the blood stream and cause deadly, systemic infections, especially in immunocompromised patients, but also in immunocompetent individuals through inserted medical devices. To survive in these diverse host environments, C. albicans has developed specialized virulence attributes and rapidly adapts itself to local growth conditions and defense mechanisms. Candida albicans secretes a considerable number of proteins that are involved in biofilm formation, tissue invasion, immune evasion, and wall maintenance, as well as acquisition of nutrients including metal ions. The secretome of C. albicans is predicted to comprise 225 proteins. On a proteomic level, however, analysis of the secretome of C. albicans is incomplete as many secreted proteins are only produced under certain conditions. Interestingly, glycosylphosphatidylinositol proteins and known cytoplasmic proteins are also consistently detected in the growth medium. Importantly, a core set of seven wall polysaccharide-processing enzymes seems to be consistently present, including the diagnostic marker Mp65. Overall, we discuss the importance of the secretome for virulence and suggest potential targets for better and faster diagnostic methods. PMID:23170918

  14. Chemical composition and antifungal potential of Brazilian propolis against Candida spp.

    PubMed

    Freires, I A; Queiroz, V C P P; Furletti, V F; Ikegaki, M; de Alencar, S M; Duarte, M C T; Rosalen, P L

    2016-06-01

    Propolis is known to have biological properties against numerous microorganisms of clinical interest. This study aimed to determine the chemical composition and antifungal activity of Brazilian propolis (types 3 and 13) against Candida spp. and their effects on the morphology of preformed and mature Candida biofilms. Samples of propolis (3 and 13) collected by Apis mellifera honeybees were obtained from different regions in Brazil. Ethanolic extracts of propolis (EEP) were prepared, fractionated and submitted to chemical analysis by GC/MS. The extracts and their hexane, dichloromethane and ethyl acetate fractions were tested for their ability to inhibit Candida spp. (C. albicans, C. dubliniensis, C. glabrata, C. kruzei, C. tropicalis and C. parapsilosis) by determination of the minimum inhibitory and fungicidal concentrations (MIC/MFC). Additionally, their effects on morphology of preformed and mature biofilms were observed by scanning electron microscopy. The phenolic compounds p-coumaric acid, caffeic acid phenethyl ester (CAPE), kaempferol and quercetin were identified in the EEP-3 and its bioactive dichloromethane fraction; and isoflavonoids such as medicarpin, vestitol and formononetin were found in the EEP-13, and triterpenes in its bioactive hexane fraction. The EEP-3 and EEP-13 and their bioactive fractions showed MIC values ranging from 0.2 to 125μg/mL and MFC values between 125 and 500μg/mL. The EEP and fractions were predominantly fungistatic agents. All extracts and fractions disrupted biofilm structures at 500μg/mL and amorphous areas with cell damage were clearly observed in preformed and mature biofilms. Propolis types 3 and 13 have strong anti-Candida activity and should be considered as promising candidates to treat oral and systemic candidiasis. PMID:26916845

  15. Epidemiology and phospholipase activity of oral Candida SPP. Among patients with central nervous system diseases before and after dental cleaning procedure.

    PubMed

    Ribeiro, Aurélia Silva; Silva, Dágma Aparecida; Silva, Francislene Pereira; Santos, Gleicy Carla; Campos, Lívia Maria Soares; Oliveira, Lorena Vivien Neves; Santos, Daniel Assis

    2010-01-01

    Patients suffering of diseases that affect central nervous system may be considered more susceptible to the infectious diseases of mouth. Sixty-nine patients suffering of cerebral palsy, Down's syndrome and metal retardation were submitted to saliva examination for the presence of Candida spp. before and after a procedure of dental cleaning. The isolates were submitted to assay for verifying phospholipase production. 55.10% of the patients provided isolation of Candida spp. The frequency of isolation obtained before dental procedure was: C. albicans (83.33%), C. krusei (8.33%) and C. kefyr, C. parapsilosis and C. glabrata (2.78% each). The frequency after the procedure was: C. albicans (68.57%), C. parapsilosis (11.43%), C. krusei and C. kefyr (8.57% each) and Candida glabrata (2.86%). We verified significantly difference (p < 0.01) between populations obtained at the two examinations. Phospholipase production was verified only among C. albicans strains and the proportion of producers was higher when testing isolates obtained after dental cleaning procedure. Studies focused on Candida spp. isolation are useful for better comprehension of the role of these yeasts on the oral flora from patients with cerebral palsy, Down's syndrome and metal retardation.

  16. Roles of IL-33 in Resistance and Tolerance to Systemic Candida albicans Infections

    PubMed Central

    Park, Sang Jun; Cho, Hong Rae

    2016-01-01

    IL-33 is a multifunctional cytokine that is released in response to a variety of intrinsic and extrinsic stimuli. The role of IL-33 in Candida albicans infections is just beginning to be revealed. This cytokine has beneficial effects on host defense against systemic C. albicans infections, and it promotes resistance mechanisms by which the immune system eliminates the invading fungal pathogens; and it also elevates host tolerance by reducing the inflammatory response and thereby, potentially, tissue damage. Thus, IL-33 is classified as a cytokine that has evolved functionally to protect the host from damage by pathogens and immunopathology. PMID:27340384

  17. Comparative Analysis of Protein Glycosylation Pathways in Humans and the Fungal Pathogen Candida albicans

    PubMed Central

    Martínez-Duncker, Iván; Díaz-Jímenez, Diana F.; Mora-Montes, Héctor M.

    2014-01-01

    Protein glycosylation pathways are present in all kingdoms of life and are metabolic pathways found in all the life kingdoms. Despite sharing commonalities in their synthesis, glycans attached to glycoproteins have species-specific structures generated by the presence of different sets of enzymes and acceptor substrates in each organism. In this review, we present a comparative analysis of the main glycosylation pathways shared by humans and the fungal pathogen Candida albicans: N-linked glycosylation, O-linked mannosylation and glycosylphosphatidylinositol-anchorage. The knowledge of similarities and divergences between these metabolic pathways could help find new pharmacological targets for C. albicans infection. PMID:25104959

  18. Dissecting Candida albicans Infection from the Perspective of C. albicans Virulence and Omics Approaches on Host–Pathogen Interaction: A Review

    PubMed Central

    Chin, Voon Kin; Lee, Tze Yan; Rusliza, Basir; Chong, Pei Pei

    2016-01-01

    Candida bloodstream infections remain the most frequent life-threatening fungal disease, with Candida albicans accounting for 70% to 80% of the Candida isolates recovered from infected patients. In nature, Candida species are part of the normal commensal flora in mammalian hosts. However, they can transform into pathogens once the host immune system is weakened or breached. More recently, mortality attributed to Candida infections has continued to increase due to both inherent and acquired drug resistance in Candida, the inefficacy of the available antifungal drugs, tedious diagnostic procedures, and a rising number of immunocompromised patients. Adoption of animal models, viz. minihosts, mice, and zebrafish, has brought us closer to unraveling the pathogenesis and complexity of Candida infection in human hosts, leading towards the discovery of biomarkers and identification of potential therapeutic agents. In addition, the advancement of omics technologies offers a holistic view of the Candida-host interaction in a non-targeted and non-biased manner. Hence, in this review, we seek to summarize past and present milestone findings on C. albicans virulence, adoption of animal models in the study of C. albicans infection, and the application of omics technologies in the study of Candida–host interaction. A profound understanding of the interaction between host defense and pathogenesis is imperative for better design of novel immunotherapeutic strategies in future. PMID:27763544

  19. Predisposing conditions for Candida spp. carriage in the oral cavity of denture wearers and individuals with natural teeth.

    PubMed

    Lyon, Juliana Pereira; da Costa, Sérgio Carvalho; Totti, Valéria Maria Gomes; Munhoz, Maira Forestti Vieira; de Resende, Maria Aparecida

    2006-05-01

    Candida species are a normal commensal present in a large percentage of healthy individuals. Denture wearers are predisposed to the development of candidosis and to the presence of Candida spp. The presence of the yeast, even in healthy subjects, should be considered more carefully. We investigated the prevalence of Candida spp. in 112 denture wearers and 103 individuals with natural teeth, patients from the clinic of total prosthesis of the Dental School of the Federal University of Minas Gerais, Brazil, and from the School of Pharmacy and Dentistry of Alfenas, Brazil. Factors like gender, age over 60 years, low education, and xerostomia were directly associated with the presence of Candida yeasts at a significance level of 5% (p > 0.05). However, the major predisposing factor for the carrier state was wearing dentures (p = 0.001). Candida isolates were identified using morphological and biochemical profiles. Seventy-one isolates were identified as C. albicans (65.1%), 15 as C. glabrata (13.7%), 8 as C. parapsilosis (7.3%), 3 as C. krusei (2.7%), and 12 as C. tropicalis (11.0%). Susceptibility testing to fluconazole and itraconazole was also performed with the strains obtained. Both drugs showed a strong inhibition against most oral isolates.

  20. Activity of antimicrobial peptide mimetics in the oral cavity: I. Activity against biofilms of Candida albicans.

    PubMed

    Hua, J; Yamarthy, R; Felsenstein, S; Scott, R W; Markowitz, K; Diamond, G

    2010-12-01

    Naturally occurring antimicrobial peptides hold promise as therapeutic agents against oral pathogens such as Candida albicans but numerous difficulties have slowed their development. Synthetic, non-peptidic analogs that mimic the properties of these peptides have many advantages and exhibit potent, selective antimicrobial activity. Several series of mimetics (with molecular weight < 1000) were developed and screened against oral Candida strains as a proof-of-principle for their antifungal properties. One phenylalkyne and several arylamide compounds with reduced mammalian cytotoxicities were found to be active against C. albicans. These compounds demonstrated rapid fungicidal activity in liquid culture even in the presence of saliva, and demonstrated synergy with standard antifungal agents. When assayed against biofilms grown on denture acrylic, the compounds exhibited potent fungicidal activity as measured by metabolic and fluorescent viability assays. Repeated passages in sub-minimum inhibitory concentration levels did not lead to resistant Candida, in contrast to fluconazole. Our results demonstrate the proof-of principle for the use of these compounds as anti-Candida agents, and their further testing is warranted as novel anti-Candida therapies.

  1. Activity of Antimicrobial Peptide Mimetics in the Oral Cavity: I. Activity Against Biofilms of Candida albicans

    PubMed Central

    Hua, Jianyuan; Yamarthy, Radha; Felsenstein, Shaina; Scott, Richard W.; Markowitz, Kenneth; Diamond, Gill

    2010-01-01

    Summary Naturally occurring antimicrobial peptides hold promise as therapeutic agents against oral pathogens such as Candida albicans, however numerous difficulties have slowed their development. Synthetic, non-peptidic analogs that mimic the properties of these peptides have many advantages and exhibit potent, selective antimicrobial activity. Several series of mimetics (MW <1,000) were developed and screened against oral Candida strains as a proof-of-principle for their antifungal properties. One phenylalkyne and several arylamide compounds with reduced mammalian cytotoxicities were found to be active against C. albicans. These compounds demonstrated rapid fungicidal activity in liquid culture even in the presence of saliva, and demonstrated synergy with standard antifungal agents. When assayed against biofilms grown on denture acrylic, the compounds exhibited potent fungicidal activity as measured by metabolic and fluorescent viability assays. Repeated passages in sub-MIC levels did not lead to resistant Candida in contrast to fluconazole. Our results demonstrate the proof-of principle for the use of these compounds as anti-Candida agents, and their further testing is warranted as novel anti-Candida therapies. PMID:21040515

  2. Function and subcellular localization of Gcn5, a histone acetyltransferase in Candida albicans.

    PubMed

    Chang, Peng; Fan, Xueyi; Chen, Jiangye

    2015-08-01

    Candida albicans is an opportunistic fungal pathogen commonly found in humans. It has the ability to switch reversibly between three growth forms: budding yeast, pseudohypha, and hypha. The transition between yeast and hyphal growth forms is critical for the pathogenesis of C. albicans. During the yeast-to-hypha morphologic transition, gene expression is regulated by transcriptional regulators including histone modifying complexes and chromatin remodeling complexes. We previously reported that Esa1, a catalytic subunit in the histone acetyltransferase complex NuA4, is essential for the hyphal development of C. albicans. In this study, we analyzed the functional roles of Gcn5, a catalytic subunit in the histone acetyltransferase complex SAGA, in C. albicans. Gcn5 is required for the invasive and filamentous growth of C. albicans. Deletion of GCN5 impaired hyphal elongation in sensing serum and attenuated the virulence of C. albicans in a mouse systemic infection model. The C. albicans gcn5/gcn5 mutant cells also exhibited sensitivity to cell wall stress. Functional analysis showed that the HAT domain and Bromodomain in Gcn5 play distinct roles in morphogenesis and cell wall stress response of C. albicans. Our results show that the conserved residue Glu188 is crucial for the Gcn5 HAT activity and for Gcn5 function during filamentous growth. In addition, the subcellular distribution of ectopically expressed GFP-Gcn5 correlates with the different growth states of C. albicans. In stationary phase, Gcn5 accumulated in the nucleus, while during vegetative growth it localized in the cytoplasm in a morpha-independent manner. Our results suggest that the nuclear localization of Gcn5 depends on the existence of its N-terminal NLS and HAT domains.

  3. Comparison of Switching and Biofilm Formation between MTL-Homozygous Strains of Candida albicans and Candida dubliniensis.

    PubMed

    Pujol, Claude; Daniels, Karla J; Soll, David R

    2015-12-01

    Candida albicans and Candida dubliniensis are highly related species that share the same main developmental programs. In C. albicans, it has been demonstrated that the biofilms formed by strains heterozygous and homozygous at the mating type locus (MTL) differ functionally, but studies rarely identify the MTL configuration. This becomes a particular problem in studies of C. dubliniensis, given that one-third of natural strains are MTL homozygous. For that reason, we have analyzed MTL-homozygous strains of C. dubliniensis for their capacity to switch from white to opaque, the stability of the opaque phenotype, CO2 induction of switching, pheromone induction of adhesion, the effects of minority opaque cells on biofilm thickness and dry weight, and biofilm architecture in comparison with C. albicans. Our results reveal that C. dubliniensis strains switch to opaque at lower average frequencies, exhibit a far lower level of opaque phase stability, are not stimulated to switch by high CO2, exhibit more variability in biofilm architecture, and most notably, form mature biofilms composed predominately of pseudohyphae rather than true hyphae. Therefore, while several traits of MTL-homozygous strains of C. dubliniensis appear to be degenerating or have been lost, others, most notably several related to biofilm formation, have been conserved. Within this context, the possibility is considered that C. dubliniensis is transitioning from a hypha-dominated to a pseudohypha-dominated biofilm and that aspects of C. dubliniensis colonization may provide insights into the selective pressures that are involved.

  4. Clusters of patients with candidaemia due to genotypes of Candida albicans and Candida parapsilosis: differences in frequency between hospitals.

    PubMed

    Marcos-Zambrano, L J; Escribano, P; Sanguinetti, M; Gómez G de la Pedrosa, E; De Carolis, E; Vella, A; Cantón, R; Bouza, E; Guinea, J

    2015-07-01

    The presence of clusters (identical genotypes infecting different patients) suggests patient-to-patient transmission or a common source for strains. We report the results of a genotyping study based on microsatellite markers of Candida albicans (n = 179) and Candida parapsilosis (n = 76) causing candidaemia, to assess and compare the percentage of patients grouped in clusters during the study period (January 2010 to December 2012). The study was performed in two large tertiary hospitals in Madrid, Spain. We detected 145 C. albicans genotypes (21 in clusters) and 63 C. parapsilosis genotypes (seven in clusters). Clusters involved two to seven patients each. Most of the clusters in the two centres involved two patients for both species, but the number of patients included in each cluster differed between hospitals. Considering both species, the percentage of patients per cluster ranged from 19% to 38% (p < 0.05) in Hospital A and B respectively. Up to 2.9% of genotypes were present in both hospitals. Clusters of C. albicans and C. parapsilosis genotypes causing candidaemia differed between hospitals, suggesting differences in strain transmission. Occasionally, the same genotypes were found in patients admitted to different hospitals located in the same city.

  5. Piperazinyl quinolines as chemosensitizers to increase fluconazole susceptibility of Candida albicans clinical isolates.

    PubMed

    Youngsaye, Willmen; Vincent, Benjamin; Hartland, Cathy L; Morgan, Barbara J; Buhrlage, Sara J; Johnston, Stephen; Bittker, Joshua A; MacPherson, Lawrence; Dandapani, Sivaraman; Palmer, Michelle; Whitesell, Luke; Lindquist, Susan; Schreiber, Stuart L; Munoz, Benito

    2011-09-15

    The effectiveness of the potent antifungal drug fluconazole is being compromised by the rise of drug-resistant fungal pathogens. While inhibition of Hsp90 or calcineurin can reverse drug resistance in Candida, such inhibitors also impair the homologous human host protein and fungal-selective chemosensitizers remain rare. The MLPCN library was screened to identify compounds that selectively reverse fluconazole resistance in a Candida albicans clinical isolate, while having no antifungal activity when administered as a single agent. A piperazinyl quinoline was identified as a new small-molecule probe (ML189) satisfying these criteria.

  6. [Killer toxin and enzyme production by Candida albicans isolated from buccal mucosa in patients with cancer].

    PubMed

    de Oliveira, E E; Silva, S C; Soares, A J; Attux, C; Cruvinel, B; Silva, M do R

    1998-01-01

    Opportunistic infections of the oral cavity are primarily caused by Candida and frequently occur in patients with cancer who are undergoing chemotherapy and antibiotic treatment. Of the specimens received from the oral mucosa of 44 patients with cancer, 25 (56.8%) yielded Candida on culture in Sabouraud agar. Twenty four of these isolates were identified as C. albicans (96%) and 1 as C. krusei (4%). The phenotypic characteristics of these isolates showed that all of them were strongly proteolytic, had a high ability to produce phospholipase, and presented the byotypes characterized as 811 (95.8%) and 511 (4.2%) in terms of susceptibility to killer toxins. PMID:9859695

  7. Antifungal drug resistance pattern of Candida. spp isolated from vaginitis in Ilam-Iran during 2013-2014

    PubMed Central

    Mohamadi, Jasem; Havasian, Mohamad Reza; Panahi, Jafar; Pakzad, Iraj

    2015-01-01

    Vaginal Candidiasis is the most common and important opportunistic fungal infection in women. By increasing use of antifungal drugs in recent years, it has caused drug resistance. This study aims to evaluate antifungal drugs susceptibility of Candida. spp isolated of women with vaginitis from Ilam-Iran during 2013-2014. samples were collected and cultured from 385 women with vaginitis, then Candida.spp was diagnosed by standard method. Antifungal drug susceptibility test for nystatin 100 unit/disk, fluconazole 10µg/disk, itraconazole 10µg/disk, ketoconazole 10µg/disk, amphotericinB 20µg/disk, clotrimazole 10µg/disk, posaconazole 5µg/disk, and voriconazole 1µg/disk were carried out by M44-A method(CLSI). From all culture positive samples, 150 isolates were Candida albicans and 89 isolates were non-albicans. The resistance to fluconazole, itraconazole, ketoconazole, clotrimazole, voriconazole, posaconazole, nystatin and amphotericin B was 76%, 62%, 72%, 55%, 6%, 7%, 1% and 0%. The highest resistance was seen for fluconazole , itraconazole, and the highest susceptible was seen for nystatin and amphotericin B. These results indicate nystatin and amphotericin B can be used as the first line for empirical therapy of vaginal candidiasis in the district. PMID:26124561

  8. Etiological significance of Candida albicans in otitis externa.

    PubMed

    Jadhav, Vijay J; Pal, M; Mishra, G S

    2003-01-01

    A study covering 79 patients (42 males, 37 females) of different age groups clinically diagnosed as otomycosis were investigated mycologically to elucidate the role of Candia albicans, an opportunistic polymorphic yeast, in otitis externa. C. albicans was diagnosed as the sole pathogen in two patients (1 male and 1 female) aged 18 and 20 years, respectively. The organism was repeatedly demonstrated in the aural specimens both by direct microscopy as well as culture isolation. Both the patients had unilateral otomycosis and used antibiotic solution and removed wax with wooden stick. The topical application of one per cent clotrimazole lotion showed good response both clinically as well as mycologically. The growing significance of opportunistic fungi emphasizes on comprehensive studies to establish the etiologic role in various clinical disorders in human and animal medicine.

  9. Antibacterial and antifungal activity of Iranian propolis against Staphylococcus aureus and Candida albicans.

    PubMed

    Ghasem, Yousef-Beigi; Ownagh, Abdolghaffar; Hasanloei, M

    2007-04-15

    Propolis samples from West North region of Iran were studied for their antibacterial (against Staphylococcus aureus) and antifungal (against Candida albicans) activities. In this article, yield of extracts and their pH values were measured. Antibacterial and antifungal activities of Ethanol-Extracted Propolis (EEP) were investigated by Petri dish bioassay method. Dilutions of EPP in agar with serial concentrations ranging from 0/04 to 10% (W/V) were prepared and antimicrobial activities were determined as Minimal Inhibitory Concentrations (MIC). All samples were active against the fungal and bacterial test strains. MIC values for different propolis samples against Staphylococcus aureus were, respectively 4, 3 and 1.5% (W/V) and against Candida albicans were, respectively 2, 4 and 3% (W/V).

  10. Anaerobic bacteria grow within Candida albicans biofilms and induce biofilm formation in suspension cultures.

    PubMed

    Fox, Emily P; Cowley, Elise S; Nobile, Clarissa J; Hartooni, Nairi; Newman, Dianne K; Johnson, Alexander D

    2014-10-20

    The human microbiome contains diverse microorganisms, which share and compete for the same environmental niches. A major microbial growth form in the human body is the biofilm state, where tightly packed bacterial, archaeal, and fungal cells must cooperate and/or compete for resources in order to survive. We examined mixed biofilms composed of the major fungal species of the gut microbiome, Candida albicans, and each of five prevalent bacterial gastrointestinal inhabitants: Bacteroides fragilis, Clostridium perfringens, Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis. We observed that biofilms formed by C. albicans provide a hypoxic microenvironment that supports the growth of two anaerobic bacteria, even when cultured in ambient oxic conditions that are normally toxic to the bacteria. We also found that coculture with bacteria in biofilms induces massive gene expression changes in C. albicans, including upregulation of WOR1, which encodes a transcription regulator that controls a phenotypic switch in C. albicans, from the "white" cell type to the "opaque" cell type. Finally, we observed that in suspension cultures, C. perfringens induces aggregation of C. albicans into "mini-biofilms," which allow C. perfringens cells to survive in a normally toxic environment. This work indicates that bacteria and C. albicans interactions modulate the local chemistry of their environment in multiple ways to create niches favorable to their growth and survival.

  11. Innate Immunity and Saliva in Candida albicans-mediated Oral Diseases.

    PubMed

    Salvatori, O; Puri, S; Tati, S; Edgerton, M

    2016-04-01

    The oral cavity is a unique niche where Candida albicans infections occur in immunocompetent as well as immunosuppressed individuals. Here we critically review the significance of human innate immune response in preventing oral candidiasis. One important line of defense against oropharyngeal candidiasis is the oral microbiota that prevents infection by competing for space and nutrients as well as by secreting antagonistic molecules and triggering local inflammatory responses. C. albicans is able to induce mucosal defenses through activation of immune cells and production of cytokines. Also, saliva contains various proteins that affect C. albicans growth positively by promoting mucosal adherence and negatively through immune exclusion and direct fungicidal activity. We further discuss the role of saliva in unifying host innate immune defenses against C. albicans as a communicating medium and how C. albicans overgrowth in the oral cavity may be a result of aberrations ranging from microbial dysbiosis and salivary dysfunction to epithelial damage. Last we underscore select oral diseases in which C. albicans is a contributory microorganism in immune-competent individuals.

  12. Commensal Protection of Staphylococcus aureus against Antimicrobials by Candida albicans Biofilm Matrix

    PubMed Central

    Kong, Eric F.; Tsui, Christina; Kucharíková, Sona; Andes, David

    2016-01-01

    ABSTRACT Biofilm-associated polymicrobial infections, particularly those involving fungi and bacteria, are responsible for significant morbidity and mortality and tend to be challenging to treat. Candida albicans and Staphylococcus aureus specifically are considered leading opportunistic fungal and bacterial pathogens, respectively, mainly due to their ability to form biofilms on catheters and indwelling medical devices. However, the impact of mixed-species biofilm growth on therapy remains largely understudied. In this study, we investigated the influence of C. albicans secreted cell wall polysaccharides on the response of S. aureus to antibacterial agents in biofilm. Results demonstrated significantly enhanced tolerance for S. aureus to drugs in the presence of C. albicans or its secreted cell wall polysaccharide material. Fluorescence confocal time-lapse microscopy revealed impairment of drug diffusion through the mixed biofilm matrix. Using C. albicans mutant strains with modulated cell wall polysaccharide expression, exogenous supplementation, and enzymatic degradation, the C. albicans-secreted β-1,3-glucan cell wall component was identified as the key matrix constituent providing the bacteria with enhanced drug tolerance. Further, antibody labeling demonstrated rapid coating of the bacteria by the C. albicans matrix material. Importantly, via its effect on the fungal biofilm matrix, the antifungal caspofungin sensitized the bacteria to the drugs. Understanding such symbiotic interactions with clinical relevance between microbial species in biofilms will greatly aid in overcoming the limitations of current therapies and in defining potential new targets for treating polymicrobial infections. PMID:27729510

  13. Hyphal formation of Candida albicans is controlled by electron transfer system

    SciTech Connect

    Watanabe, Toshihiko . E-mail: twatanab@tohoku-pharm.ac.jp; Ogasawara, Ayako; Mikami, Takeshi; Matsumoto, Tatsuji

    2006-09-15

    Most Candida albicans cells cultured in RPMI1640 medium at 37 deg. C grow in hyphal form in aerobic conditions, but they grow in yeast form in anaerobic conditions. The hyphal growth of C. albicans was inhibited in glucose-deficient conditions. Malonic acid, an inhibitor of succinate dehydrogenase, enhanced the yeast proliferation of C. albicans, indicating that the hyphal-formation signal was derived from the glycolysis system and the signal was transmitted to the electron transfer system via the citric acid cycle. Thenoyl trifluoro acetone (TTFA), an inhibitor of the signal transmission between complex II and Co Q, significantly inhibited the hyphal growth of C. albicans. Antimycin, KCN, and oligomycin, inhibitors of complex III, IV, and V, respectively, did not inhibit the hyphal growth of C. albicans. The production of mRNAs for the hyphal formation signal was completely inhibited in anaerobic conditions. These results indicate that the electron transfer system functions upstream of the RAS1 signal pathway and activates the expression of the hyphal formation signal. Since the electron transfer system is inactivated in anaerobic conditions, C. albicans grew in yeast form in this condition.

  14. Antifungal Activity of Bee Venom and Sweet Bee Venom against Clinically Isolated Candida albicans

    PubMed Central

    Lee, Seung-Bae

    2016-01-01

    Objectives: The purpose of this study was to investigate the antifungal effect of bee venom (BV) and sweet bee venom (SBV) against Candida albicans (C. albicans) clinical isolates. Methods: In this study, BV and SBV were examined for antifungal activities against the Korean Collection for Type Cultures (KCTC) strain and 10 clinical isolates of C. albicans. The disk diffusion method was used to measure the antifungal activity and minimum inhibitory concentration (MIC) assays were performed by using a broth microdilution method. Also, a killing curve assay was conducted to investigate the kinetics of the anti- fungal action. Results: BV and SBV showed antifungal activity against 10 clinical isolates of C. albicans that were cultured from blood and the vagina by using disk diffusion method. The MIC values obtained for clinical isolates by using the broth microdilution method varied from 62.5 μg/ mL to 125 μg/mL for BV and from 15.63 μg/mL to 62.5 μg/mL for SBV. In the killing-curve assay, SBV behaved as amphotericin B, which was used as positive control, did. The antifungal efficacy of SBV was much higher than that of BV. Conclusion: BV and SBV showed antifungal activity against C. albicans clinical strains that were isolated from blood and the vagina. Especially, SBV might be a candidate for a new antifungal agent against C. albicans clinical isolates. PMID:27280049

  15. Specific induction of fibronectin binding activity by hemoglobin in Candida albicans grown in defined media.

    PubMed

    Yan, S; Nègre, E; Cashel, J A; Guo, N; Lyman, C A; Walsh, T J; Roberts, D D

    1996-08-01

    Fibronectin (FN) is a major component of host extracellular matrix that may play an important role in the initiation and dissemination of Candida albicans infections. Expression of FN binding requires growth of C albicans blastoconidia in complex medium, and the regulation of FN receptor expression is poorly understood. We now demonstrate that hemoglobin is a potent and specific inducer of FN receptor expression and describe a defined medium supplemented with hemoglobin that greatly and stably enhances the binding activity of C. albicans for soluble FN. Enhancement of FN binding by hemoglobin in strain 44807 was concentration dependent and was maximal at 0.1% hemoglobin with 20- to 80-fold enhancement. The hemoglobin-induced FN binding to C. albicans was saturable, with a Kd of 2.7 X 10(-8) M. Enhancement required growth of C. albicans in hemoglobin-containing medium, since simply exposing blastoconidia to hemoglobin in a nongrowing status did not enhance binding. Induction was reversible following removal of hemoglobin from the growth medium and not associated with germination. Inorganic or protein-bound iron was not sufficient for the induction, since other iron-containing proteins or inorganic iron salts were inactive. Growth in the simple medium yeast nitrogen base supplemented with hemoglobin increased cell adhesion to immobilized FN and to cultured monolayers of bovine corneal endothelial cells. These data suggest that hemoglobin may be an important regulator of FN binding activity in C. albicans and thus may play a role in its pathogenesis. PMID:8757815

  16. Innate Immunity and Saliva in Candida albicans-mediated Oral Diseases.

    PubMed

    Salvatori, O; Puri, S; Tati, S; Edgerton, M

    2016-04-01

    The oral cavity is a unique niche where Candida albicans infections occur in immunocompetent as well as immunosuppressed individuals. Here we critically review the significance of human innate immune response in preventing oral candidiasis. One important line of defense against oropharyngeal candidiasis is the oral microbiota that prevents infection by competing for space and nutrients as well as by secreting antagonistic molecules and triggering local inflammatory responses. C. albicans is able to induce mucosal defenses through activation of immune cells and production of cytokines. Also, saliva contains various proteins that affect C. albicans growth positively by promoting mucosal adherence and negatively through immune exclusion and direct fungicidal activity. We further discuss the role of saliva in unifying host innate immune defenses against C. albicans as a communicating medium and how C. albicans overgrowth in the oral cavity may be a result of aberrations ranging from microbial dysbiosis and salivary dysfunction to epithelial damage. Last we underscore select oral diseases in which C. albicans is a contributory microorganism in immune-competent individuals. PMID:26747422

  17. Identification of the cell targets important for propolis-induced cell death in Candida albicans.

    PubMed

    de Castro, Patrícia Alves; Bom, Vinícius Leite Pedro; Brown, Neil Andrew; de Almeida, Ricardo Sérgio Couto; Ramalho, Leandra Naira Zambelli; Savoldi, Marcela; Goldman, Maria Helena S; Berretta, Andresa A; Goldman, Gustavo Henrique

    2013-11-01

    Candida albicans is the most common fungal pathogen of humans, forming both commensal and opportunistic pathogenic interactions, causing a variety of skin and soft tissue infections in healthy people. In immunocompromised patients C. albicans can result in invasive, systemic infections that are associated with a high incidence of mortality. Propolis is a complex mixture of several resinous substances which are collected from plants by bees. Here, we demonstrated the fungicidal activity of propolis against all three morphogenetic types of C. albicans and that propolis-induced cell death was mediated via metacaspase and Ras signaling. To identify genes that were involved in propolis tolerance, we screened ~800 C. albicans homozygous deletion mutants for decreased tolerance to propolis. Fifty-one mutant strains were identified as being hypersensitive to propolis including seventeen genes involved in cell adhesion, biofilm formation, filamentous growth, phenotypic switching and pathogenesis (HST7, GIN4, VPS34, HOG1, ISW2, SUV3, MDS3, HDA2, KAR3, YHB1, NUP85, CDC10, MNN9, ACE2, FKH2, and SNF5). We validated these results by showing that propolis inhibited the transition from yeast-like to hyphal growth. Propolis was shown to contain compounds that conferred fluorescent properties to C. albicans cells. Moreover, we have shown that a topical pharmaceutical preparation, based upon propolis, was able to control C. albicans infections in a mouse model for vulvovaginal candidiasis. Our results strongly indicate that propolis could be used as a strategy for controlling candidiasis.

  18. Potent Synergy between Spirocyclic Pyrrolidinoindolinones and Fluconazole against Candida albicans

    PubMed Central

    Premachandra, Ilandari Dewage Udara Anulal; Scott, Kevin A.; Shen, Chengtian; Wang, Fuqiang; Lane, Shelley; Liu, Haoping

    2015-01-01

    A spiroindolinone (1S,3R,3aR,6aS)-1-benzyl-6′-chloro-5-(4-fluorophenyl)-7′-methylspiro[1,2,3a,6a-tetrahydropyrrolo[3,4-c]pyrrole-3,3′-1H-indole]-2′,4,6-trione was previously reported to enhance the antifungal effect of fluconazole against C. albicans. A diastereomer of that compound was synthesized, along with various analogues. Many of the compounds were shown to enhance the antifungal effect of fluconazole against C. albicans, some with exquisite potency. One spirocyclic piperazine derivative, which we have named synazo-1, enhanced the effect of fluconazole with EC50 of 300 pM against a susceptible strain of C. albicans and as low as 2 nM against some resistant strains. Synazo-1 exhibits true synergy with fluconazole with an FIC index below 0.5 in the strains tested. Synazo-1 exhibited low toxicity in mammalian cells relative to the concentrations required for the antifungal synergy. PMID:26263912

  19. Members of the Candida parapsilosis Complex and Candida albicans are Differentially Recognized by Human Peripheral Blood Mononuclear Cells

    PubMed Central

    Estrada-Mata, Eine; Navarro-Arias, María J.; Pérez-García, Luis A.; Mellado-Mojica, Erika; López, Mercedes G.; Csonka, Katalin; Gacser, Attila; Mora-Montes, Héctor M.

    2016-01-01

    The systemic infections caused by members of the Candida parapsilosis complex are currently associated to high morbility and mortality rates, and are considered as relevant as those caused by Candida albicans. Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). We found that the wall of the C. parapsilosis complex members is similar in composition, but differs to that from C. albicans, with less mannan content and more β-glucan and porosity levels. Furthermore, lectin-based analysis showed increased chitin and β1,3-glucan exposure at the surface of C. parapsilosis sensu lato when compared to C. albicans. Yeast cells of members of the C. parapsilosis complex stimulated more cytokine production by human PBMCs than C. albicans cells; and this significantly changed upon removal of O-linked mannans, indicating this wall component plays a significant role in cytokine stimulation by C. parapsilosis sensu lato. When inner wall components were exposed on the wall surface, C. parapsilosis sensu stricto and C. metapsilosis, but not C. orthopsilosis, stimulated higher cytokine production. Moreover, we found a strong dependency on β1,3-glucan recognition for the members of the C. parapsilosis complex, but not for live C. albicans cells; whereas TLR4 was required for TNFα production by the three members of the complex, and stimulation of IL-6 by C. orthopsilosis. Mannose receptor had a significant role during TNFα and IL-1β stimulation by members of the complex. Finally, we demonstrated that purified N- and O-mannans from either C. parapsilosis sensu lato or C. albicans are capable to block the recognition of these pathogens by human PBMCs. Together; our results suggest that the innate immune recognition of the members of the C. parapsilosis complex is differential

  20. Mixed Fungal Lung Infection with Aspergillus Fumigatus and Candida Albicans in a Immunocomprimised Patient: Case Report

    PubMed Central

    Vipparti, Haritha

    2014-01-01

    The frequency of invasive, opportunistic mycoses has increased significantly over the past 2 decades. In the immune-compromised host, many fungi, including species of fungi typically considered non-pathogenic, have the potential to cause serious morbidity and mortality. Here we report a rare case of mixed fungal infection of the lung with Candida albicans and Aspergillus fumigatus in a patient on prolonged steroid therapy. PMID:24959447

  1. Candida albicans blastoconidia in peripheral blood smears from non-neutropenic surgical patients.

    PubMed

    Berrouane, Y; Bisiau, H; Le Baron, F; Cattoen, C; Duthilleul, P; Dei Cas, E

    1998-07-01

    An 80 year old woman developed fever 11 days after volvulus surgery. A peripheral blood smear showed numerous yeast cells--both extraleucocytic and intraleucocytic--as well as leucoagglutination. The fungal elements included blastospores, pseudohyphae, and germ tubes. Two days later, blood cultures yielded Candida albicans, Enterobacter aerogenes, and Staphlococcus aureus. The patient had no medical history of immunodeficiency. Several reports indicate that fungal elements may be detected in peripheral blood smears from patients who have a severe intestinal disease.

  2. ML212: A small-molecule probe for investigating fluconazole resistance mechanisms in Candida albicans

    PubMed Central

    Youngsaye, Willmen; Hartland, Cathy L; Morgan, Barbara J; Ting, Amal; Nag, Partha P; Vincent, Benjamin; Mosher, Carrie A; Bittker, Joshua A; Dandapani, Sivaraman; Palmer, Michelle; Whitesell, Luke; Lindquist, Susan; Schreiber, Stuart L

    2013-01-01

    Summary The National Institutes of Health Molecular Libraries and Probe Production Centers Network (NIH-MLPCN) screened >300,000 compounds to evaluate their ability to restore fluconazole susceptibility in resistant Candida albicans isolates. Additional counter screens were incorporated to remove substances inherently toxic to either mammalian or fungal cells. A substituted indazole possessing the desired bioactivity profile was selected for further development, and initial investigation of structure–activity relationships led to the discovery of ML212. PMID:23946849

  3. Ultrastructure of Candida albicans pleomorphic forms: phase-contrast microscopy, scanning and transmission electron microscopy.

    PubMed

    Staniszewska, Monika; Bondaryk, Małgorzata; Siennicka, Katarzyna; Kurzatkowski, Wiesław

    2012-01-01

    A modified method of glutaraldeyde-osmium tetroxide fixation was adjusted to characterize the ultrastructure of Candida albicans pleomorphic forms, using phase-contrast microscopy, scanning electron microscopy and transmission electron microscopy. The discovered morphological criteria defining the individual morphotypes are discussed in terms of mycological and histopathological diagnostics of candidiasis. The relations are discussed between fungal pleomorphism, virulence and susceptibility of different morphotypes to fungicides.

  4. Suppression of humoral response during the course of Candida albicans infection in mice.

    PubMed

    Valdez, J C; Meson, O E; de Valdez, G A; Sirena, A

    1984-10-30

    This paper aims at demonstrating the non-specific immunosuppression as regards thyme-dependent antigens sheep erythrocytes (SRBC) during the course of Candida albicans systemic infection. Three lots of syngeneic/BALB/c mice, 8-12 weeks of age, were used. The first normal lot was inoculated via the intraperitoneal route with a (SRBC) suspension (4 X 10(8) cells ml) in a Hank's balanced saline solution. The primary response of antibodies formed by splenic cells was measured from 4 to 8 days after inoculation using the direct plaque forming cells technique. The second lot was infected by the same route with a suspension of Candida albicans (1 X 10(7) cells). Positive retrocultures from the blood and kidneys of these infected mice were obtained. These yeasts cultivated in a Sabouraud medium were harvested after 20 h at 37 degrees C. Following the same methodology the immune response to SRBC was determined. The serum obtained from infected mice was transferred to a third lot of mice at different intervals during the course of the infection. The immune response to SRBC was done by the direct plaque-forming cells technique. Controls were carried out using normal donors and recipients. A suppression of the immune response was obtained as from the 2nd day of inoculation up to the 28th day. It was not possible to transfer such suppression passively by means of the serum. These results suggest that the systemic infection by Candida albicans induce a non-specific immunosuppression in the organism, already demonstrated in viral infections, bacteria, protozoaria and metazoaria in mammals. In some way, this will contribute to explain the mechanisms of immune response to Candida albicans.

  5. Ibuprofen potentiates the in vivo antifungal activity of fluconazole against Candida albicans murine infection.

    PubMed

    Costa-de-Oliveira, Sofia; Miranda, Isabel M; Silva-Dias, Ana; Silva, Ana P; Rodrigues, Acácio G; Pina-Vaz, Cidália

    2015-07-01

    Candida albicans is the most prevalent cause of fungemia worldwide. Its ability to develop resistance in patients receiving azole antifungal therapy is well documented. In a murine model of systemic infection, we show that ibuprofen potentiates fluconazole antifungal activity against a fluconazole-resistant strain, drastically reducing the fungal burden and morbidity. The therapeutic combination of fluconazole with ibuprofen may constitute a new approach for the management of antifungal therapeutics to reverse the resistance conferred by efflux pump overexpression.

  6. Suppression of humoral response during the course of Candida albicans infection in mice.

    PubMed

    Valdez, J C; Meson, O E; de Valdez, G A; Sirena, A

    1984-10-30

    This paper aims at demonstrating the non-specific immunosuppression as regards thyme-dependent antigens sheep erythrocytes (SRBC) during the course of Candida albicans systemic infection. Three lots of syngeneic/BALB/c mice, 8-12 weeks of age, were used. The first normal lot was inoculated via the intraperitoneal route with a (SRBC) suspension (4 X 10(8) cells ml) in a Hank's balanced saline solution. The primary response of antibodies formed by splenic cells was measured from 4 to 8 days after inoculation using the direct plaque forming cells technique. The second lot was infected by the same route with a suspension of Candida albicans (1 X 10(7) cells). Positive retrocultures from the blood and kidneys of these infected mice were obtained. These yeasts cultivated in a Sabouraud medium were harvested after 20 h at 37 degrees C. Following the same methodology the immune response to SRBC was determined. The serum obtained from infected mice was transferred to a third lot of mice at different intervals during the course of the infection. The immune response to SRBC was done by the direct plaque-forming cells technique. Controls were carried out using normal donors and recipients. A suppression of the immune response was obtained as from the 2nd day of inoculation up to the 28th day. It was not possible to transfer such suppression passively by means of the serum. These results suggest that the systemic infection by Candida albicans induce a non-specific immunosuppression in the organism, already demonstrated in viral infections, bacteria, protozoaria and metazoaria in mammals. In some way, this will contribute to explain the mechanisms of immune response to Candida albicans. PMID:6392889

  7. Ibuprofen Potentiates the In Vivo Antifungal Activity of Fluconazole against Candida albicans Murine Infection

    PubMed Central

    Miranda, Isabel M.; Silva-Dias, Ana; Silva, Ana P.; Rodrigues, Acácio G.; Pina-Vaz, Cidália

    2015-01-01

    Candida albicans is the most prevalent cause of fungemia worldwide. Its ability to develop resistance in patients receiving azole antifungal therapy is well documented. In a murine model of systemic infection, we show that ibuprofen potentiates fluconazole antifungal activity against a fluconazole-resistant strain, drastically reducing the fungal burden and morbidity. The therapeutic combination of fluconazole with ibuprofen may constitute a new approach for the management of antifungal therapeutics to reverse the resistance conferred by efflux pump overexpression. PMID:25845879

  8. Identification of the aminocatechol A-3253 as an in vitro poison of DNA topoisomerase I from Candida albicans.

    PubMed Central

    Fostel, J; Montgomery, D

    1995-01-01

    The aminocatechol A-3253 is active against several pathogenic fungi, including Candida albicans, Cryptococcus albidus, and Aspergillus niger. A-3253 interferes with both the in vitro biosynthesis of (1,3)-beta-glucan and the activity of topoisomerases I isolated from Candida spp. It is likely that one or more of the enzymes involved in glucan biosynthesis rather than topoisomerase I is the primary intracellular target of A-3253, since a strain of Saccharomyces cerevisiae lacking topoisomerase I is as susceptible to A-3253 as cells containing wild-type levels of topoisomerase I. However, the interaction of A-3253 with topoisomerase I in vitro is of interest since the Candida topoisomerase is more susceptible to A-3253 than is the topoisomerase I isolated from human HeLa cells. A-3253 is both a reversible inhibitor of topoisomerase I catalysis and a reversible poison of topoisomerase I, and in both reactions the fungal topoisomerase I is more susceptible than the human topoisomerase I to A-3253. In contrast, an earlier study found that the human topoisomerase I is more susceptible than the fungal topoisomerase to camptothecin (J. M. Fostel, D. A. Montgomery, and L. L. Shen, Antimicrob. Agents Chemother. 36:2131-2138, 1992). Taken together with the response to camptothecin, the greater susceptibility of the Candida topoisomerase I to A-3253 suggests that there are structural differences between the human and fungal type I topoisomerases which can likely be exploited to allow for the development of antifungal agents which act against the fungal topoisomerase and which have minimal activity against the human enzyme. PMID:7793856

  9. Manipulation of Host Diet To Reduce Gastrointestinal Colonization by the Opportunistic Pathogen Candida albicans

    PubMed Central

    Tornberg-Belanger, Stephanie N.; Matthan, Nirupa R.; Lichtenstein, Alice H.

    2015-01-01

    ABSTRACT Candida albicans, the most common human fungal pathogen, can cause systemic infections with a mortality rate of ~40%. Infections arise from colonization of the gastrointestinal (GI) tract, where C. albicans is part of the normal microflora. Reducing colonization in at-risk patients using antifungal drugs prevents C. albicans-associated mortalities. C. albicans provides a clinically relevant system for studying the relationship between diet and the microbiota as it relates to commensalism and pathogenicity. As a first step toward a dietary intervention to reduce C. albicans GI colonization, we investigated the impact of dietary lipids on murine colonization by C. albicans. Coconut oil and its constituent fatty acids have antifungal activity in vitro; we hypothesized that dietary coconut oil would reduce GI colonization by C. albicans. Colonization was lower in mice fed a coconut oil-rich diet than in mice fed diets rich in beef tallow or soybean oil. Switching beef tallow-fed mice to a coconut oil diet reduced preexisting colonization. Coconut oil reduced colonization even when the diet also contained beef tallow. Dietary coconut oil also altered the metabolic program of colonizing C. albicans cells. Long-chain fatty acids were less abundant in the cecal contents of coconut oil-fed mice than in the cecal contents of beef tallow-fed mice; the expression of genes involved in fatty acid utilization was lower in C. albicans from coconut oil-fed mice than in C. albicans from beef tallow-fed mice. Extrapolating to humans, these findings suggest that coconut oil could become the first dietary intervention to reduce C. albicans GI colonization. IMPORTANCE Candida albicans, the most common human fungal pathogen, can cause infections with a mortality rate of ~40%. C. albicans is part of the normal gut flora, but when a patient’s immune system is compromised, it can leave the gut and cause infections. By reducing the amount of C. albicans in the gut of

  10. Manipulation of Host Diet To Reduce Gastrointestinal Colonization by the Opportunistic Pathogen Candida albicans.

    PubMed

    Gunsalus, Kearney T W; Tornberg-Belanger, Stephanie N; Matthan, Nirupa R; Lichtenstein, Alice H; Kumamoto, Carol A

    2016-01-01

    Candida albicans, the most common human fungal pathogen, can cause systemic infections with a mortality rate of ~40%. Infections arise from colonization of the gastrointestinal (GI) tract, where C. albicans is part of the normal microflora. Reducing colonization in at-risk patients using antifungal drugs prevents C. albicans-associated mortalities. C. albicans provides a clinically relevant system for studying the relationship between diet and the microbiota as it relates to commensalism and pathogenicity. As a first step toward a dietary intervention to reduce C. albicans GI colonization, we investigated the impact of dietary lipids on murine colonization by C. albicans. Coconut oil and its constituent fatty acids have antifungal activity in vitro; we hypothesized that dietary coconut oil would reduce GI colonization by C. albicans. Colonization was lower in mice fed a coconut oil-rich diet than in mice fed diets rich in beef tallow or soybean oil. Switching beef tallow-fed mice to a coconut oil diet reduced preexisting colonization. Coconut oil reduced colonization even when the diet also contained beef tallow. Dietary coconut oil also altered the metabolic program of colonizing C. albicans cells. Long-chain fatty acids were less abundant in the cecal contents of coconut oil-fed mice than in the cecal contents of beef tallow-fed mice; the expression of genes involved in fatty acid utilization was lower in C. albicans from coconut oil-fed mice than in C. albicans from beef tallow-fed mice. Extrapolating to humans, these findings suggest that coconut oil could become the first dietary intervention to reduce C. albicans GI colonization. IMPORTANCE Candida albicans, the most common human fungal pathogen, can cause infections with a mortality rate of ~40%. C. albicans is part of the normal gut flora, but when a patient's immune system is compromised, it can leave the gut and cause infections. By reducing the amount of C. albicans in the gut of susceptible

  11. Eugenol and thymol, alone or in combination, induce morphological alterations in the envelope of Candida albicans.

    PubMed

    Braga, P C; Sasso, M Dal; Culici, M; Alfieri, M

    2007-09-01

    The envelope of Candida albicans, with its outermost array of macromolecules protruding towards the environment, is pivotal to the expression of major virulence factors such as adhesiveness, and the morphological transition to hyphal form. We tested the anticandidal activity of eugenol, main component of clove oil, and thymol, main component of thyme oil, alone or in combination, by investigating their ability to interfere with the architecture of the envelope of C. albicans. Both molecules alterated the morphogenesis of the envelope, but the effects of thymol were more pronounced than those of eugenol. Certain combinations of the two molecules led to a synergistic effect, which is interesting in the view of potentiating their inhibition of C. albicans colonisation and infectiousness. PMID:17590533

  12. Oral Immunization Against Candidiasis Using Lactobacillus casei Displaying Enolase 1 from Candida albicans

    PubMed Central

    Shibasaki, Seiji; Karasaki, Miki; Tafuku, Senji; Aoki, Wataru; Sewaki, Tomomitsu; Ueda, Mitsuyoshi

    2014-01-01

    Abstract Candidiasis is a common fungal infection that is prevalent in immunocompromised individuals. In this study, an oral vaccine against Candida albicans was developed by using the molecular display approach. Enolase 1 protein (Eno1p) of C. albicans was expressed on the Lactobacillus casei cell surface by using poly-gamma-glutamic acid synthetase complex A from Bacillus subtilis as an anchoring protein. The Eno1p-displaying L. casei cells were used to immunize mice, which were later challenged with a lethal dose of C. albicans. The data indicated that the vaccine elicited a strong IgG response and increased the survival rate of the vaccinated mice. Furthermore, L. casei acted as a potent adjuvant and induced high antibody titers that were comparable to those induced by strong adjuvants such as the cholera toxin. Overall, the molecular display method can be used to rapidly develop vaccines that can be conveniently administered and require minimal processing. PMID:25853077

  13. Effect of ferrocene-substituted porphyrin RL-91 on Candida albicans biofilm formation.

    PubMed

    Lippert, Rainer; Vojnovic, Sandra; Mitrovic, Aleksandra; Jux, Norbert; Ivanović-Burmazović, Ivana; Vasiljevic, Branka; Stankovic, Nada

    2014-08-01

    Ferrocene-substituted porphyrin RL-91 exhibits antifungal activity against opportune human pathogen Candida albicans. RL-91 efficiently inhibits growth of both planktonic C. albicans cells and cells within biofilms without photoactivation. The minimal inhibitory concentration for plankton form (PMIC) was established to be 100 μg/mL and the same concentration killed 80% of sessile cells in the mature biofilm (SMIC80). Furthermore PMIC of RL-91 efficiently prevents C. albicans biofilm formation. RL-91 is cytotoxic for human fibroblasts in vitro in concentration of 10 μg/mL, however it does not cause hemolysis in concentrations of up to 50 μg/mL. These findings open possibility for application of RL-91 as an antifungal agent for external antibiofilm treatment of medical devices as well as a scaffold for further development of porphyrin based systemic antifungals.

  14. The Role of Autophagy-Related Proteins in Candida albicans Infections

    PubMed Central

    Tam, Jenny M.; Mansour, Michael K.; Acharya, Mridu; Sokolovska, Anna; Timmons, Allison K.; Lacy-Hulbert, Adam; Vyas, Jatin M.

    2016-01-01

    Autophagy plays an important role in maintaining cell homeostasis by providing nutrients during periods of starvation and removing damaged organelles from the cytoplasm. A marker in the autophagic process is the reversible conjugation of LC3, a membrane scaffolding protein, to double membrane autophagosomes. Recently, a role for LC3 in the elimination of pathogenic bacteria and fungi, including Candida albicans (C. albicans), was demonstrated, but these organisms reside in single membrane phagosomes. This process is distinct from autophagy and is termed LC3-associated phagocytosis (LAP). This review will detail the hallmarks of LAP that distinguish it from classical autophagy and review the role of autophagy proteins in host response to C. albicans and other pathogenic fungi. PMID:27043636

  15. Protocol for Determination of the Persister Subpopulation in Candida Albicans Biofilms.

    PubMed

    De Brucker, Katrijn; De Cremer, Kaat; Cammue, Bruno P A; Thevissen, Karin

    2016-01-01

    In contrast to planktonic cultures of the human fungal pathogen Candida albicans, C. albicans biofilms can contain a persister subpopulation that is tolerant to high concentrations of currently used antifungals. In this chapter, the method to determine the persister fraction in a C. albicans biofilm treated with an antifungal compound is described. To this end, a mature biofilm is developed and subsequently treated with a concentration series of the antifungal compound of interest. Upon incubation, the fraction of surviving biofilm cells is determined by plating and plotted versus the used concentrations of the antifungal compound. If a persister subpopulation in the biofilm is present, the dose-dependent killing of the biofilm cells results in a biphasic killing pattern.

  16. In vitro effects of glycyrrhetinic acid on the growth of clinical isolates of Candida albicans.

    PubMed

    Pellati, Donatella; Fiore, Cristina; Armanini, Decio; Rassu, Mario; Bertoloni, Giulio

    2009-04-01

    Compounds derived from Glycyrrhiza glabra L. root have been used widely for centuries for their numerous therapeutic properties. The present study aimed to test the in vitro activity against Candida albicans strains of the compound 18-beta glycyrrhetinic acid (18-beta GA), derived from the root of Glycyrrhiza species. This antimicrobial activity was assessed using the National Committee for Clinical Laboratory Standards (NCCLS) method on C. albicans strains that were isolated from patients with recurrent vulvovaginal candidiasis (RVVC). The in vitro growth of the C. albicans strains was markedly reduced, in a pH-dependent manner, by relatively low doses (6.2 microg/mL) of 18-beta GA. The results demonstrate that 18-beta GA is a promising biological alternative for the topical treatment of recurrent vulvovaginal candidiasis (RVVC). PMID:19067381

  17. Acute labyrinthitis associated with systemic Candida albicans infection in ageing mice.

    PubMed

    Ashman, R B; Papadimitriou, J M; Fulurija, A

    1996-01-01

    The yeast Candida albicans is an important opportunistic pathogen that has been associated with disease of the inner ear. This study describes the histopathology of acute labyrinthitis caused by systemic infection with C. albicans in aging inbred mice. Within four days after infection, yeast and hyphal forms of C.albicans were found in the membranous labyrinth. The utricle and the adjacent parts of the ampullary regions of the semicircular canals were most severely affected, but damage was also seen in the scala media, the scala tympani, the saccule, and the scala vestibuli. In the utricle, the lining epithelium of the membranous labyrinth was disrupted, and the lining cells of the vestibular membrane showed foci in which the membrane was disrupted. The data suggest that age may represent a risk factor for fungal labyrinthitis.

  18. D-Erythroascorbic acid activates cyanide-resistant respiration in Candida albicans.

    PubMed

    Huh, Won-Ki; Song, Yong Bhum; Lee, Young-Seok; Ha, Cheol Woong; Kim, Seong-Tae; Kang, Sa-Ouk

    2008-05-01

    Higher plants, protists and fungi possess cyanide-resistant respiratory pathway, which is mediated by alternative oxidase (AOX). The activity of AOX has been found to be dependent on several regulatory mechanisms including gene expression and posttranslational regulation. In the present study, we report that the presence of cyanide in culture medium remarkably retarded the growth of alo1/alo1 mutant of Candida albicans, which lacks d-arabinono-1,4-lactone oxidase (ALO) that catalyzes the final step of d-erythroascorbic acid (EASC) biosynthesis. Measurement of respiratory activity and Western blot analysis revealed that increase in the intracellular EASC level induces the expression of AOX in C. albicans. AOX could still be induced by antimycin A, a respiratory inhibitor, in the absence of EASC, suggesting that several factors may act in parallel pathways to induce the expression of AOX. Taken together, our results suggest that EASC plays important roles in activation of cyanide-resistant respiration in C. albicans.

  19. Modulation of Candida albicans attachment to human epithelial cells by bacteria and carbohydrates.

    PubMed Central

    Centeno, A; Davis, C P; Cohen, M S; Warren, M M

    1983-01-01

    The effects of carbohydrates (mannose and dextrose). Escherichia coli 07KL. and Klebsiella pneumoniae on Candida albicans attachment to epithelial cells was studied. Dextrose had no effect on yeast attachment to epithelial cells. Conversely, mannose significantly decreased both yeast and piliated bacterial attachment (E. coli 07KL, heavily piliated K. pneumoniae) whereas having no effect on nonpiliated K. pneumoniae attachment to epithelial cells. The number of yeasts attaching to epithelial cells was enhanced by preincubation of epithelial cells with piliated strains of bacteria, whereas preincubation with nonpiliated strains of bacteria had no effect on yeast attachment. Scanning electron microscopy showed that piliated bacteria and yeasts were juxtaposed on the epithelial cell surface. These data suggest that certain piliated strains of bacteria can enhance C. albicans attachment to epithelial cells and that type 1 pili of bacteria can be a factor in the enhanced attachment of C. albicans to epithelial cells. Images PMID:6132878

  20. Effect of sodium bicarbonate on Candida albicans adherence to thermally activated acrylic resin.

    PubMed

    Sousa, Fernando Augusto Cervantes Garcia de; Paradella, Thaís Cachuté; Koga-Ito, Cristiane Yumi; Jorge, Antonio Olavo Cardoso

    2009-01-01

    The purpose of this study was to evaluate the effect of 5% sodium bicarbonate on the adherence of Candida albicans to thermally activated acrylic resin. Fifty 4 mm(2) specimens of acrylic resin were obtained using a metallic matrix. The specimens received chemical polishing, were sterilized and then immersed in Sabouraud broth, inoculated with Candida albicans standardized suspension. After 24 hours of incubation at 37 degrees Celsius, the specimens were divided into four groups according to the substance used for disinfection (5% sodium bicarbonate, 0.12% digluconate chlorhexidine, vinegar and Corega Tabs). A control group was included, in which distilled water was used. The adhered microorganisms were dispersed, diluted and plated onto culture media to determine the number of colony-forming units (cfu/mL). The results were analyzed through the Mann-Whitney statistical test at the 5% level of significance. Only 0.12% digluconate chlorhexidine and 5% sodium bicarbonate presented a statistically significant difference (p = 0.0010 and p = 0.0156, respectively) compared to the control group, decreasing the number of cfu/mL. However, when the different disinfecting solutions were compared with each other, only 0.12% digluconate chlorhexidine presented a statistically significant difference in the reduction of cfu/mL. It was concluded that although 0.12% digluconate chlorhexidine was more effective in the reduction of Candida albicans adherence values to thermally activated acrylic resin, 5% sodium bicarbonate also proved to be a viable alternative. PMID:20027444

  1. Analysis of the relationship between fluconazole consumption and non-C. albicans Candida infections.

    PubMed

    Tyczkowska-Sieron, E; Gaszynski, W; Tyczkowski, J; Glowacka, A

    2014-10-01

    The effect of fluconazole consumption on the incidence of nosocomial non-C. albicans Candida infections remains unclear. In this study we investigated such a relationship in an intensive care unit (Poland) over an 11-year period (2002-2012). Statistics relating to the number of candidiasis cases and the number of defined daily doses of fluconazole showed that only a very weak and not statistically significant linear correlation existed between these two variables (r(2) = 0.36, P = 0.052). However, the assumption of a 1-year delay in the infection response to changes in fluconazole concentrations resulted in a strong and statistically significant linear correlation (r(2) = 0.64, P = 0.0053). To more accurately determine the nature of this relationship, a simple epidemiological model was proposed that provided a better than linear correlation (r(2) = 0.78, P = 0.00077). We successfully used this approach to analyze results from the literature that were interpreted as evidence that fluconazole use is not a risk factor for development of non-C. albicans Candida infections. If a time delay in the infection response was assumed, a strong and statistically significant correlation was obtained. These findings suggest the need for a closer look at fluconazole therapy as a possible risk factor for development of non-C. albicans Candida infections.

  2. DLH1 is a functional Candida albicans homologue of the meiosis-specific gene DMC1

    SciTech Connect

    Diener, A.C.; Fink, G.R.

    1996-06-01

    DMC1/LIM15 homologue 1 (DLH1), a gene related to meiosis-specific genes, has been isolated from Candida albicans, a fungus thought not to undergo meiosis. The deduced protein sequence of DLH1 contains 74% amino acid identity with Dmc1p from Saccharomyces cerevisiae and 63% with Lim15p from the plant Lilium longiflorum, meiosis-specific homologous of Escherichia coli RecA. Candida DLH1 complements a dmc1/dmc1 null mutant in S. cerevisiae. High copy expression of DLH1 restores both sporulation and meiotic recombination to a Saccharomyces dmc1/{Delta}/dmc1{Delta} strain. Unlike the DMC1 gene, which is transcribed only in meiotic cells, the heterologous Candida DLH1 gene is transcribed in both vegetative and meiotic cells of S. cerevisiae. Transcription of DLH1 is not detected or induced in C. albicans under conditions that induce DMC1 and meiosis in S. cerevisiae. The presence of an intact homologue of a meiosis-specific gene in C. albicans raises the possibility that this organism has a cryptic meiotic pathway. 25 refs., 6 figs., 3 tabs.

  3. Effect of two monoterpene phenols on antioxidant defense system in Candida albicans.

    PubMed

    Khan, Amber; Ahmad, Aijaz; Ahmad Khan, Luqman; Padoa, Carolyn J; van Vuuren, Sandy; Manzoor, Nikhat

    2015-03-01

    Thymol and carvacrol from the class of monoterpene phenols are one of the most potent plant essential oil components possessing antimicrobial effects. Known for their wide bioactive spectrum, these positional isomers of isopropyl cresol deplete ergosterol content, compromise membrane permeability, block efflux pumps and restore antifungal susceptibility to fluconazole in resistant Candida strains. Exposure to these natural compounds induces a cascade of stress responses, which are important to comprehend their microbicidal mechanisms. This study evaluates the antioxidant defense response to lower concentrations of thymol and carvacrol in Candida albicans. The antioxidant defense responses in C. albicans are important for developmental mechanisms pertaining to resistance against the immune system, infection establishment and drug resistance. In this view, primary and secondary antioxidant defense enzymes, and oxidative stress markers including glutathione and lipid peroxidation were determined in C. albicans cells exposed to lower concentrations of thymol and carvacrol. These compounds were found to induce oxidative stress and compromised the antioxidant defense system in C. albicans at lower concentrations. This study helps in understanding the 'in cell' antifungal mechanisms of natural monoterpene phenols originating from oxidative stress. Thymol and carvacrol induced membrane deterioration reported earlier, is further explained as a result of a toxic radical cascade mediated by lipid peroxidation. Findings reinforce the observed toxic oxidizing effects of these compounds as a consequence of direct damage to antioxidant components and not to their genetic manipulations. PMID:25681060

  4. Application of surface plasmon resonance biosensor for the detection of Candida albicans

    NASA Astrophysics Data System (ADS)

    Yodmongkol, Sirasa; Thaweboon, Sroisiri; Thaweboon, Boonyanit; Puttharugsa, Chokchai; Sutapun, Boonsong; Amarit, Ratthasart; Somboonkaew, Armote; Srikhirin, Toemsak

    2016-02-01

    In this study, surface plasmon resonance imaging (SPR imaging) was developed for the detection of Candida albicans which is a causal agent of oral infection. The detection was based on the sandwich assay. The capture antibody was covalently immobilized on the mixed self assemble monolayers (SAMs). The ratio of mixed SAMs between 11-mercaptoundecanoic acid and 3-mercaptopropanol was varied to find the optimal ratio for use as a sensor surface. The results showed that the suitable surface for C. albicans detection was SAM of carboxylic (mixed SAMs 1:0), even though mixed SAMs 1:40 had a high detection signal in comparison to mixed SAMs 1:0, but the non-specific signal was higher. The detection limit was 107 cells/ml for direct detection, and was increased to 106 cells/ml with sandwich antibody. The use of polyclonal C. albicans antibody as capture and sandwich antibody showed good selectivity against the relevant oral bacteria including Escherichia coli, Streptococcus mutan, Staphylococcus aureus, β-streptococci, and Lactobacillus casei. SPR platform in this study could detect C. albicans from the mixed microbial suspension without requirement of skillful technician. This SPR imaging biosensor could be applied for Candida identification after cultivation.

  5. Nanoscopic cell-wall architecture of an immunogenic ligand in Candida albicans during antifungal drug treatment

    PubMed Central

    Lin, Jia; Wester, Michael J.; Graus, Matthew S.; Lidke, Keith A.; Neumann, Aaron K.

    2016-01-01

    The cell wall of Candida albicans is composed largely of polysaccharides. Here we focus on β-glucan, an immunogenic cell-wall polysaccharide whose surface exposure is often restricted, or “masked,” from immune recognition by Dectin-1 on dendritic cells (DCs) and other innate immune cells. Previous research suggested that the physical presentation geometry of β-glucan might determine whether it can be recognized by Dectin-1. We used direct stochastic optical reconstruction microscopy to explore the fine structure of β-glucan exposed on C. albicans cell walls before and after treatment with the antimycotic drug caspofungin, which alters glucan exposure. Most surface-accessible glucan on C. albicans yeast and hyphae is limited to isolated Dectin-1–binding sites. Caspofungin-induced unmasking caused approximately fourfold to sevenfold increase in total glucan exposure, accompanied by increased phagocytosis efficiency of DCs for unmasked yeasts. Nanoscopic imaging of caspofungin-unmasked C. albicans cell walls revealed that the increase in glucan exposure is due to increased density of glucan exposures and increased multiglucan exposure sizes. These findings reveal that glucan exhibits significant nanostructure, which is a previously unknown physical component of the host–Candida interaction that might change during antifungal chemotherapy and affect innate immune activation. PMID:26792838

  6. Biofilm formation and Candida albicans morphology on the surface of denture base materials.

    PubMed

    Susewind, Sabine; Lang, Reinhold; Hahnel, Sebastian

    2015-12-01

    Fungal biofilms may contribute to the occurrence of denture stomatitis. The objective of the study was to investigate the biofilm formation and morphology of Candida albicans in biofilms on the surface of denture base materials. Specimens were prepared from different denture base materials. After determination of surface properties and salivary pellicle formation, mono- and multispecies biofilm formation including Candida albicans ATCC 10231 was initiated. Relative amounts of adherent cells were determined after 20, 44, 68 and 188 h; C. albicans morphology was analysed employing selective fluorescence microscopic analysis. Significant differences were identified in the relative amount of cells adherent to the denture base materials. Highest blastospore/hyphae index suggesting an increased percentage of hyphae was observed in mono- and multispecies biofilms on the soft denture liner, which did not necessarily respond to the highest relative amount of adherent cells. For both biofilm models, lowest relative amount of adherent cells was identified on the methacrylate-based denture base material, which did not necessarily relate to a significantly lower blastospore/hyphae index. The results indicate that there are significant differences in both biofilm formation as well as the morphology of C. albicans cells in biofilms on the surface of different denture base materials.

  7. Top-down characterization data on the speciation of the Candida albicans immunome in candidemia.

    PubMed

    Pitarch, Aida; Nombela, César; Gil, Concha

    2016-03-01

    The characterization of pathogen-specific antigenic proteins at the protein species level is crucial in the development and molecular optimization of novel immunodiagnostics, vaccines or immunotherapeutics for infectious diseases. The major requirements to achieve this molecular level are to obtain 100% sequence coverage and identify all post-translational modifications of each antigenic protein species. In this article, we show nearly complete sequence information for five discrete antigenic species of Candida albicans Tdh3 (glyceraldehyde-3-phosphate dehydrogenase), which have been reported to be differentially recognized both among candidemia patients and between candidemia and control patients. A comprehensive description of the top-down immunoproteomic strategy used for seroprofiling at the C. albicans protein species level in candidemia as well as for the chemical characterization of this immunogenic protein (based on high-resolution 2-DE, Western blotting, peptide mass fingerprinting, tandem mass spectrometry and de novo peptide sequencing) is also provided. The top-down characterization data on the speciation of the C. albicans immunome in candidemia presented here are related to our research article entitled "Seroprofiling at the Candida albicans protein species level unveils an accurate molecular discriminator for candidemia" (Pitarch et al., J. Proteomics, 2015, http://dx.doi.org/10.1016/j.jprot.2015.10.022). PMID:26862568

  8. Application of benzo[a]phenoxazinium chlorides in Antimicrobial Photodynamic Therapy of Candida albicans biofilms.

    PubMed

    Lopes, Marisa; Alves, Carlos Tiago; Rama Raju, B; Gonçalves, M Sameiro T; Coutinho, Paulo J G; Henriques, Mariana; Belo, Isabel

    2014-12-01

    The use of Antimicrobial Photodynamic Therapy (APDT) as a new approach to treat localized Candida infections is an emerging and promising field nowadays. The aim of this study was to verify the efficacy of photodynamic therapy using two new benzo[a]phenoxazinium photosensitizers against Candida albicans biofilms: N-(5-(3-hydroxypropylamino)-10-methyl-9H-benzo[a]phenoxazin-9-ylidene)ethanaminium chloride (FSc) and N-(5-(11-hydroxyundecylamino)-10-methyl-9H-benzo[a]phenoxazin-9-ylidene)ethanaminium chloride (FSd). The photodynamic activity of dyes against C. albicans biofilms was evaluated by incubating biofilms with dyes in the range of 100-300 μM for 3 or 18 h followed by illumination at 12 or 36 J cm(-2), using a xenon arc lamp (600 ± 2 nm). A total photoinactivation of C. albicans biofilm cells was achieved using 300 μM of FSc with 18 h of incubation, followed by illumination at 36 J cm(-2). Contrarily, FSd had insignificant effect on biofilms inactivation by APDT. The higher uptake of FSc than FSd dye by biofilms during the dark incubation may explain the greater photodynamic effectiveness achieved with FSc. The results obtained stresses out the FSc-mediated APDT potential use to treat C. albicans infections.

  9. The effect of thyme and tea tree oils on morphology and metabolism of Candida albicans.

    PubMed

    Rajkowska, Katarzyna; Kunicka-Styczyńska, Alina; Maroszyńska, Marta; Dąbrowska, Mariola

    2014-01-01

    Members of Candida species cause significant problems in medicine and in many industrial branches also. In order to prevent from Candida sp. development, essential oils are more and more frequently applied as natural, non-toxic, non-pollutive and biodegradable agents with a broad spectrum of antimicrobial activity. The aim of the research was to determine changes in morphology and metabolic properties of Candida albicans in the presence of thyme and tea tree oils. Changes of enzymatic activity of isolates were observed in the presence of both tested essential oils, and they were primarily associated with loss or decrease of activity of all enzymes detected for control. Furthermore, only for 3 out of 11 isolates additional activity of N-acetyl-β-glucosaminidase, α-mannosidase, α-fucosidase and trypsin was detected. Vivid changes in biochemical profiles were found after treatment with tea tree oil and they were related to loss of ability to assimilate D-xylose, D-sorbitol and D-trehalose. The main differences in morphology of isolates compared to the control strain concerned formation of pseudohyphae structures. Both examined essential oils caused changes in cell and colony morphology, as well as in the metabolism of Candida albicans. However, the extent of differences depends on the type and concentration of an essential oil. The most important finding is the broad spectrum of changes in yeast enzymatic profiles induced by thyme and tea tree oils. It can be supposed that these changes, together with loss of ability to assimilate saccharides could significantly impact Candida albicans pathogenicity.

  10. The effect of thyme and tea tree oils on morphology and metabolism of Candida albicans.

    PubMed

    Rajkowska, Katarzyna; Kunicka-Styczyńska, Alina; Maroszyńska, Marta; Dąbrowska, Mariola

    2014-01-01

    Members of Candida species cause significant problems in medicine and in many industrial branches also. In order to prevent from Candida sp. development, essential oils are more and more frequently applied as natural, non-toxic, non-pollutive and biodegradable agents with a broad spectrum of antimicrobial activity. The aim of the research was to determine changes in morphology and metabolic properties of Candida albicans in the presence of thyme and tea tree oils. Changes of enzymatic activity of isolates were observed in the presence of both tested essential oils, and they were primarily associated with loss or decrease of activity of all enzymes detected for control. Furthermore, only for 3 out of 11 isolates additional activity of N-acetyl-β-glucosaminidase, α-mannosidase, α-fucosidase and trypsin was detected. Vivid changes in biochemical profiles were found after treatment with tea tree oil and they were related to loss of ability to assimilate D-xylose, D-sorbitol and D-trehalose. The main differences in morphology of isolates compared to the control strain concerned formation of pseudohyphae structures. Both examined essential oils caused changes in cell and colony morphology, as well as in the metabolism of Candida albicans. However, the extent of differences depends on the type and concentration of an essential oil. The most important finding is the broad spectrum of changes in yeast enzymatic profiles induced by thyme and tea tree oils. It can be supposed that these changes, together with loss of ability to assimilate saccharides could significantly impact Candida albicans pathogenicity. PMID:24918492

  11. Adding Biotin to Parenteral Nutrition Solutions Without Lipid Accelerates the Growth of Candida albicans

    PubMed Central

    Kuwahara, Takashi; Kaneda, Shinya; Shimono, Kazuyuki

    2016-01-01

    Background: We have previously demonstrated that Candida albicans requires multivitamins (MVs) or lipid to increase rapidly in parenteral nutrition (PN) solutions. In this study, in detail, the effects of vitamins on the growth of C. albicans in PN solutions without lipid were investigated. Methods: In the 1st experiment, a commercial PN solution without lipid was supplemented with water-soluble vitamins (SVs: vitamins B1, B2, B6, B12 and C, folic acid, nicotinamide, biotin and panthenol), water-insoluble vitamins (IVs: vitamins A, D, E and K) or both (MVs). In the 2nd experiment, the test solutions were prepared by supplementing the PN solution with one of each or all of the SVs. In the 3rd experiment, another commercial peripheral PN (PPN) solution without lipid was supplemented with SVs, nicotinic acid, biotin or both nicotinic acid and biotin. In each of the experiments, a specified number of C. albicans organisms was added to each test solution, and all of the test solutions were allowed to stand at room temperature (23-26ºC). The number of C. albicans was counted at 0, 24, 48 and 72 hours after the addition of the organism. Results: In the 1st experiment, the C. albicans increased rapidly in the PN solution supplemented with the SVs, but increased slowly without the SVs, regardless of the addition of the IVs. In the 2nd experiment, the C. albicans increased rapidly in the PN solution supplemented with the SVs or biotin, but increased slowly with each of the other water-soluble vitamins. In the 3rd experiment, the C. albicans increased rapidly in the PPN solution supplemented with the SVs or biotin, but increased slowly with the addition of nicotinic acid. Conclusions: These results suggested that adding MVs or SVs to PN solutions without lipid promotes the growth of C. albicans, and that this effect is mostly attributable to biotin. PMID:27648003

  12. Adding Biotin to Parenteral Nutrition Solutions Without Lipid Accelerates the Growth of Candida albicans

    PubMed Central

    Kuwahara, Takashi; Kaneda, Shinya; Shimono, Kazuyuki

    2016-01-01

    Background: We have previously demonstrated that Candida albicans requires multivitamins (MVs) or lipid to increase rapidly in parenteral nutrition (PN) solutions. In this study, in detail, the effects of vitamins on the growth of C. albicans in PN solutions without lipid were investigated. Methods: In the 1st experiment, a commercial PN solution without lipid was supplemented with water-soluble vitamins (SVs: vitamins B1, B2, B6, B12 and C, folic acid, nicotinamide, biotin and panthenol), water-insoluble vitamins (IVs: vitamins A, D, E and K) or both (MVs). In the 2nd experiment, the test solutions were prepared by supplementing the PN solution with one of each or all of the SVs. In the 3rd experiment, another commercial peripheral PN (PPN) solution without lipid was supplemented with SVs, nicotinic acid, biotin or both nicotinic acid and biotin. In each of the experiments, a specified number of C. albicans organisms was added to each test solution, and all of the test solutions were allowed to stand at room temperature (23-26ºC). The number of C. albicans was counted at 0, 24, 48 and 72 hours after the addition of the organism. Results: In the 1st experiment, the C. albicans increased rapidly in the PN solution supplemented with the SVs, but increased slowly without the SVs, regardless of the addition of the IVs. In the 2nd experiment, the C. albicans increased rapidly in the PN solution supplemented with the SVs or biotin, but increased slowly with each of the other water-soluble vitamins. In the 3rd experiment, the C. albicans increased rapidly in the PPN solution supplemented with the SVs or biotin, but increased slowly with the addition of nicotinic acid. Conclusions: These results suggested that adding MVs or SVs to PN solutions without lipid promotes the growth of C. albicans, and that this effect is mostly attributable to biotin.

  13. Structure and regulation of the HSP90 gene from the pathogenic fungus Candida albicans.

    PubMed Central

    Swoboda, R K; Bertram, G; Budge, S; Gooday, G W; Gow, N A; Brown, A J

    1995-01-01

    Candida albicans HSP90 sequences were isolated by screening cDNA and genomic libraries with a probe derived from the Saccharomyces cerevisiae homolog, HSP82, which encodes a member of the heat shock protein 90 family of molecular chaperones. Identical sequences were obtained for the 2,197-bp overlap of the cDNA and gene sequences, which were derived from C. albicans 3153A and ATCC 10261, respectively. The C. albicans HSP90 gene contained no introns, and it showed strong homology (61 to 79% identity) to HSP90 sequences from other fungi, vertebrates, and plants. The C-terminal portion of the predicted Hsp90 amino acid sequence was identical to the 47-kDa protein which is thought to be immunoprotective during C. albicans infections (R. C. Matthews, J. Med. Microbiol. 36:367-370, 1992), confirming that this protein represents the C-terminal portion of the 81-kDa Hsp90 protein. Quantitative Northern (RNA) analyses revealed that C. albicans HSP90 mRNA was heat shock inducible and that its levels changed during batch growth, with its maximum levels being reached during the mid-exponential growth phase. HSP90 mRNA levels increased transiently during the yeast-to-hyphal transition but did not correlate directly with germ tube production per se. These data do not exclude a role for Hsp90 in the dimorphic transition. Southern blotting revealed only one HSP90 locus in the diploid C. albicans genome. Repeated attempts to disrupt both alleles and generate a homozygous C. albicans delta hsp90/delta hsp90 null mutant were unsuccessful. These observations suggest the existence of a single HSP90 locus which is essential for viability in C. albicans. PMID:7591093

  14. Recurrent candidaemia and pacemaker wire infection with Candida albicans.

    PubMed

    Glöckner, A

    2011-12-01

    Recurrent candidaemia is both a cause and a symptom of deep organ candidiasis or infection of foreign bodies (e.g. central venous line, other indwelling catheter or pacemaker wire) and is associated with significant morbidity and mortality. This case report demonstrates that in the event of pacemaker wire infection with Candida and when it is not possible to remove the infected pacemaker wire, treatment with an echinocandin, such as anidulafungin, can be safe and successful.

  15. Sensitization of Candida albicans biofilms to fluconazole by terpenoids of plant origin.

    PubMed

    Doke, Sonali Kashinath; Raut, Jayant Shankar; Dhawale, Shashikant; Karuppayil, Sankunny Mohan

    2014-01-01

    Infections associated with the biofilms of Candida albicans are a challenge to antifungal treatment. Combinatorial therapy involving plant molecules with antifungal drugs would be an effective complementary approach against drug-resistant Candida biofilms. The aim of this study was to evaluate the efficacy of three bioactive terpenoids (carvacrol, eugenol and thymol) in combination with fluconazole against planktonic cells, biofilm development and mature biofilms of C. albicans. Activities of the selected molecules were tested using a microplate-based methodology, while their combinations with fluconazole were performed in a checkerboard format. Biofilms were quantitated by XTT-metabolic assay and confirmed by microscopic observations. Combinations of carvacrol and eugenol with fluconazole were found synergistic against planktonic growth of C. albicans, while that of thymol with fluconazole did not have any interaction. Biofilm development and mature biofilms were highly resistant to fluconazole, but susceptible to three terpenoids. Sensitization of cells by sub-inhibitory concentrations of carvacrol and eugenol resulted in prevention of biofilm formation at low fluconazole concentrations, i.e. 0.032 and 0.002 mg ml(-1), respectively. Addition of thymol could not potentiate activity of fluconazole against biofilm formation by C. albicans. Fractional inhibitory concentration indices (FICI) for carvacrol-fluconazole and eugenol-fluconazole combinations for biofilm formation were 0.311 and 0.25, respectively. The FICI value of 1.003 indicated a status of indifference for the combination of thymol and fluconazole against biofilm formation. Eugenol and thymol combinations with fluconazole did not have useful interaction against mature biofilms of C. albicans, but the presence of 0.5 mg ml(-1) of carvacrol caused inhibition of mature biofilms at a significantly low concentration (i.e. 0.032 mg ml(-1)) of fluconazole. The study indicated that carvacrol and eugenol

  16. Dithiocarbamates are strong inhibitors of the beta-class fungal carbonic anhydrases from Cryptococcus neoformans, Candida albicans and Candida glabrata.

    PubMed

    Monti, Simona Maria; Maresca, Alfonso; Viparelli, Francesca; Carta, Fabrizio; De Simone, Giuseppina; Mühlschlegel, Fritz A; Scozzafava, Andrea; Supuran, Claudiu T

    2012-01-15

    A series of N-mono- and N,N-disubstituted dithiocarbamates have been investigated as inhibitors of three β-carbonic anhydrases (CAs, EC 4.2.1.1) from the fungal pathogens Cryptococcus neoformans, Candida albicans and Candida glabrata, that is, Can2, CaNce103 and CgNce103, respectively. These enzymes were inhibited with efficacies between the subnanomolar to the micromolar range, depending on the substitution pattern at the nitrogen atom from the dithiocarbamate zinc-binding group. This new class of β-CA inhibitors may have the potential for developing antifungal agents with a diverse mechanism of action compared to the clinically used drugs for which drug resistance was reported, and may also explain the efficacy of dithiocarbamates as agricultural antifungal agents. PMID:22209456

  17. Cloning and Characterization of PRA1, a Gene Encoding a Novel pH-Regulated Antigen of Candida albicans

    PubMed Central

    Sentandreu, Maria; Elorza, M. Victoria; Sentandreu, Rafael; Fonzi, William A.

    1998-01-01

    Candida albicans is an opportunistic fungal pathogen of humans. The cell wall of the organism defines the interface between the pathogen and host tissues and is likely to play an essential and pivotal role in the host-pathogen interaction. The components of the cell wall critical to this interaction are undefined. Immunoscreening of a lambda expression library with sera raised against mycelial cell walls of C. albicans was used to identify genes encoding cell surface proteins. One of the positive clones represented a candidal gene that was differentially expressed in response to changes in the pH of the culture medium. Maximal expression occurred at neutral pH, with no expression detected below pH 6.0. On the basis of the expression pattern, the corresponding gene was designated PRA1, for pH-regulated antigen. The protein predicted from the nucleotide sequence was 299 amino acids long with motifs characteristic of secreted glycoproteins. The predicted surface localization and N glycosylation of the protein were directly demonstrated by cell fractionation and immunoblot analysis. Deletion of the gene imparted a temperature-dependent defect in hypha formation, indicating a role in morphogenesis. The PRA1 protein was homologous to surface antigens of Aspergillus spp. which react with serum from aspergillosis patients, suggesting that the PRA1 protein may have a role in the host-parasite interaction during candidal infection. PMID:9440517

  18. The Effect of Essential Oils and Bioactive Fractions on Streptococcus mutans and Candida albicans Biofilms: A Confocal Analysis

    PubMed Central

    Freires, Irlan Almeida; Bueno-Silva, Bruno; Galvão, Lívia Câmara de Carvalho; Duarte, Marta Cristina Teixeira; Sartoratto, Adilson; Figueira, Glyn Mara; de Alencar, Severino Matias; Rosalen, Pedro Luiz

    2015-01-01

    The essential oils (EO) and bioactive fractions (BF) from Aloysia gratissima, Baccharis dracunculifolia, Coriandrum sativum, Cyperus articulatus, and Lippia sidoides were proven to have strong antimicrobial activity on planktonic microorganisms; however, little is known about their effects on the morphology or viability of oral biofilms. Previously, we determined the EO/fractions with the best antimicrobial activity against Streptococcus mutans and Candida spp. In this report, we used a confocal analysis to investigate the effect of these EO and BF on the morphology of S. mutans biofilms (thickness, biovolume, and architecture) and on the metabolic viability of C. albicans biofilms. The analysis of intact treated S. mutans biofilms showed no statistical difference for thickness in all groups compared to the control. However, a significant reduction in the biovolume of extracellular polysaccharides and bacteria was observed for A. gratissima and L. sidoides groups, indicating that these BF disrupt biofilm integrity and may have created porosity in the biofilm. This phenomenon could potentially result in a weakened structure and affect biofilm dynamics. Finally, C. sativum EO drastically affected C. albicans viability when compared to the control. These results highlight the promising antimicrobial activity of these plant species and support future translational research on the treatment of dental caries and oral candidiasis. PMID:25821503

  19. The Effect of Essential Oils and Bioactive Fractions on Streptococcus mutans and Candida albicans Biofilms: A Confocal Analysis.

    PubMed

    Freires, Irlan Almeida; Bueno-Silva, Bruno; Galvão, Lívia Câmara de Carvalho; Duarte, Marta Cristina Teixeira; Sartoratto, Adilson; Figueira, Glyn Mara; de Alencar, Severino Matias; Rosalen, Pedro Luiz

    2015-01-01

    The essential oils (EO) and bioactive fractions (BF) from Aloysia gratissima, Baccharis dracunculifolia, Coriandrum sativum, Cyperus articulatus, and Lippia sidoides were proven to have strong antimicrobial activity on planktonic microorganisms; however, little is known about their effects on the morphology or viability of oral biofilms. Previously, we determined the EO/fractions with the best antimicrobial activity against Streptococcus mutans and Candida spp. In this report, we used a confocal analysis to investigate the effect of these EO and BF on the morphology of S. mutans biofilms (thickness, biovolume, and architecture) and on the metabolic viability of C. albicans biofilms. The analysis of intact treated S. mutans biofilms showed no statistical difference for thickness in all groups compared to the control. However, a significant reduction in the biovolume of extracellular polysaccharides and bacteria was observed for A. gratissima and L. sidoides groups, indicating that these BF disrupt biofilm integrity and may have created porosity in the biofilm. This phenomenon could potentially result in a weakened structure and affect biofilm dynamics. Finally, C. sativum EO drastically affected C. albicans viability when compared to the control. These results highlight the promising antimicrobial activity of these plant species and support future translational research on the treatment of dental caries and oral candidiasis. PMID:25821503

  20. Impaired killing of Candida albicans by granulocytes mobilized for transfusion purposes: a role for granule components

    PubMed Central

    Gazendam, Roel P.; van de Geer, Annemarie; van Hamme, John L.; Tool, Anton T.J.; van Rees, Dieke J.; Aarts, Cathelijn E.M.; van den Biggelaar, Maartje; van Alphen, Floris; Verkuijlen, Paul; Meijer, Alexander B.; Janssen, Hans; Roos, Dirk; van den Berg, Timo K.; Kuijpers, Taco W.

    2016-01-01

    Granulocyte transfusions are used to treat neutropenic patients with life-threatening bacterial or fungal infections that do not respond to anti-microbial drugs. Donor neutrophils that have been mobilized with granulocyte-colony stimulating factor (G-CSF) and dexamethasone are functional in terms of antibacterial activity, but less is known about their fungal killing capacity. We investigated the neutrophil-mediated cytotoxic response against C. albicans and A. fumigatus in detail. Whereas G-CSF/dexamethasone-mobilized neutrophils appeared less mature as compared to neutrophils from untreated controls, these cells exhibited normal ROS production by the NADPH oxidase system and an unaltered granule mobilization capacity upon stimulation. G-CSF/dexamethasone-mobilized neutrophils efficiently inhibited A. fumigatus germination and killed Aspergillus and Candida hyphae, but the killing of C. albicans yeasts was distinctly impaired. Following normal Candida phagocytosis, analysis by mass spectrometry of purified phagosomes after fusion with granules demonstrated that major constituents of the antimicrobial granule components, including major basic protein (MBP), were reduced. Purified MBP showed candidacidal activity, and neutrophil-like Crisp-Cas9 NB4-KO-MBP differentiated into phagocytes were impaired in Candida killing. Together, these findings indicate that G-CSF/dexamethasone-mobilized neutrophils for transfusion purposes have a selectively impaired capacity to kill Candida yeasts, as a consequence of an altered neutrophil granular content. PMID:26802050

  1. Impaired killing of Candida albicans by granulocytes mobilized for transfusion purposes: a role for granule components.

    PubMed

    Gazendam, Roel P; van de Geer, Annemarie; van Hamme, John L; Tool, Anton T J; van Rees, Dieke J; Aarts, Cathelijn E M; van den Biggelaar, Maartje; van Alphen, Floris; Verkuijlen, Paul; Meijer, Alexander B; Janssen, Hans; Roos, Dirk; van den Berg, Timo K; Kuijpers, Taco W

    2016-05-01

    Granulocyte transfusions are used to treat neutropenic patients with life-threatening bacterial or fungal infections that do not respond to anti-microbial drugs. Donor neutrophils that have been mobilized with granulocyte-colony stimulating factor (G-CSF) and dexamethasone are functional in terms of antibacterial activity, but less is known about their fungal killing capacity. We investigated the neutrophil-mediated cytotoxic response against C. albicans and A. fumigatus in detail. Whereas G-CSF/dexamethasone-mobilized neutrophils appeared less mature as compared to neutrophils from untreated controls, these cells exhibited normal ROS production by the NADPH oxidase system and an unaltered granule mobilization capacity upon stimulation. G-CSF/dexamethasone-mobilized neutrophils efficiently inhibited A. fumigatus germination and killed Aspergillus and Candida hyphae, but the killing of C. albicans yeasts was distinctly impaired. Following normal Candida phagocytosis, analysis by mass spectrometry of purified phagosomes after fusion with granules demonstrated that major constituents of the antimicrobial granule components, including major basic protein (MBP), were reduced. Purified MBP showed candidacidal activity, and neutrophil-like Crisp-Cas9 NB4-KO-MBP differentiated into phagocytes were impaired in Candida killing. Together, these findings indicate that G-CSF/dexamethasone-mobilized neutrophils for transfusion purposes have a selectively impaired capacity to kill Candida yeasts, as a consequence of an altered neutrophil granular content. PMID:26802050

  2. A Candida albicans Strain Expressing Mammalian Interleukin-17A Results in Early Control of Fungal Growth during Disseminated Infection

    PubMed Central

    Huppler, Anna R.; Whibley, Natasha; Woolford, Carol A.; Childs, Erin E.; He, Jie; Biswas, Partha S.; McGeachy, Mandy J.; Mitchell, Aaron P.

    2015-01-01

    Candida albicans is normally a commensal fungus of the human mucosae and skin, but it causes life-threatening systemic infections in hospital settings in the face of predisposing conditions, such as indwelling catheters, abdominal surgery, or antibiotic use. Immunity to C. albicans involves various immune parameters, but the cytokine interleukin-17A (IL-17A) (also known as IL-17) has emerged as a centrally important mediator of immune defense against both mucosal and systemic candidiasis. Conversely, IL-17A has been suggested to enhance the virulence of C. albicans, indicating that it may exert detrimental effects on pathogenesis. In this study, we hypothesized that a C. albicans strain expressing IL-17A would exhibit reduced virulence in vivo. To that end, we created a Candida-optimized expression cassette encoding murine IL-17A, which was transformed into the DAY286 strain of C. albicans. Candida-derived IL-17A was indistinguishable from murine IL-17A in terms of biological activity and detection in standard enzyme-linked immunosorbent assays (ELISAs). Expression of IL-17A did not negatively impact the growth of these strains in vitro. Moreover, the IL-17A-expressing C. albicans strains showed significantly reduced pathogenicity in a systemic model of Candida infection, mainly evident during the early stages of disease. Collectively, these findings suggest that IL-17A mitigates the virulence of C. albicans. PMID:26150537

  3. In vivo immune responses to Candida albicans modified by treatment with recombinant murine gamma interferon.

    PubMed

    Garner, R E; Kuruganti, U; Czarniecki, C W; Chiu, H H; Domer, J E

    1989-06-01

    The immunologic effects of in vivo administration of recombinant murine gamma interferon (rMuIFN-gamma) were determined in a murine model of candidiasis. Naive mice were given graded doses of rMuIFN-gamma and then challenged intravenously with Candida albicans. Increased morbidity and mortality were noted in four different strains of mice, viz., BALB/c, A/J, Swiss Webster, and CBA/J, providing the mice had not been immunized with C. albicans before challenge. Quantitative culture of selected organs of Swiss Webster and CBA/J mice surviving treatment with rMuIFN-gamma revealed elevated numbers of C. albicans cells, particularly in the kidneys, but also in the liver, lungs, and spleen. The lungs, livers, and spleen of female CBA/J mice were more protected from increased multiplication of the fungus than were those of males of the same species or female Swiss Webster mice. On the basis of these initial findings, the effect of treatment with 5,000 U of rMuIFN-gamma on immune responses in a gastrointestinal model of candidiasis was determined. CBA/J mice that had been colonized with C. albicans as infants were boosted with a cutaneous inoculation of the fungus when 6 to 10 weeks old; development of delayed hypersensitivity (DH), antibodies, and protective responses was assayed at intervals thereafter. Daily treatment with rMuIFN-gamma (beginning 1 day before cutaneous inoculation) suppressed weak immune responses but had little effect on responses which were strong. For example, DH and anti-C. albicans antibody production were suppressed in animals colonized with C. albicans but not boosted by cutaneous inoculation, and DH was suppressed in uncolonized animals that had been inoculated once cutaneously with the fungus as well. There was no rMuIFN-gamma-induced suppressive effect of DH in mice which had been stimulated maximally with C. albicans, i.e., colonized animals that had been boosted cutaneously with the organisms. Collectively, these data indicate that naive mice

  4. In vivo immune responses to Candida albicans modified by treatment with recombinant murine gamma interferon.

    PubMed Central

    Garner, R. E.; Kuruganti, U.; Czarniecki, C. W.; Chiu, H. H.; Domer, J. E.

    1989-01-01

    The immunologic effects of in vivo administration of recombinant murine gamma interferon (rMuIFN-gamma) were determined in a murine model of candidiasis. Naive mice were given graded doses of rMuIFN-gamma and then challenged intravenously with Candida albicans. Increased morbidity and mortality were noted in four different strains of mice, viz., BALB/c, A/J, Swiss Webster, and CBA/J, providing the mice had not been immunized with C. albicans before challenge. Quantitative culture of selected organs of Swiss Webster and CBA/J mice surviving treatment with rMuIFN-gamma revealed elevated numbers of C. albicans cells, particularly in the kidneys, but also in the liver, lungs, and spleen. The lungs, livers, and spleen of female CBA/J mice were more protected from increased multiplication of the fungus than were those of males of the same species or female Swiss Webster mice. On the basis of these initial findings, the effect of treatment with 5,000 U of rMuIFN-gamma on immune responses in a gastrointestinal model of candidiasis was determined. CBA/J mice that had been colonized with C. albicans as infants were boosted with a cutaneous inoculation of the fungus when 6 to 10 weeks old; development of delayed hypersensitivity (DH), antibodies, and protective responses was assayed at intervals thereafter. Daily treatment with rMuIFN-gamma (beginning 1 day before cutaneous inoculation) suppressed weak immune responses but had little effect on responses which were strong. For example, DH and anti-C. albicans antibody production were suppressed in animals colonized with C. albicans but not boosted by cutaneous inoculation, and DH was suppressed in uncolonized animals that had been inoculated once cutaneously with the fungus as well. There was no rMuIFN-gamma-induced suppressive effect of DH in mice which had been stimulated maximally with C. albicans, i.e., colonized animals that had been boosted cutaneously with the organisms. Collectively, these data indicate that naive mice

  5. Azole-resistant Candida albicans from a wild Brazilian porcupine (Coendou prehensilis): a sign of an environmental imbalance?

    PubMed

    Castelo-Branco, D S C M; Brilhante, R S N; Paiva, M A N; Teixeira, C E C; Caetano, E P; Ribeiro, J F; Cordeiro, R A; Sidrim, J J C; Monteiro, A J; Rocha, M F G

    2013-07-01

    This study aimed at evaluating the in vitro antifungal susceptibility of Candida albicans isolates obtained during necropsy of a wild Brazilian porcupine and the mechanism of azole resistance. Initially, we investigated the in vitro susceptibility of the three isolates to amphotericin B, caspofungin, fluconazole, itraconazole, ketoconazole and voriconazole. Afterwards, three sub-inhibitory concentrations (47, 21 and 12 mg/l) of promethazine, an efflux pump inhibitor, were tested in combination with the antifungal drugs in order to evaluate the role of these pumps in the development of antifungal resistance. In addition, the three isolates were submitted to RAPD-PCR and M13-fingerprinting analyses. The minimum inhibitory concentrations (MICs) obtained with the isolates were 1, 0.03125, 250, 125, 8 and 250 mg/l for amphotericin B, caspofungin, fluconazole, itraconazole, ketoconazole and voriconazole, respectively, and the isolates were found to be resistant to all tested azoles. The addition of the three subinhibitory concentrations of promethazine resulted in statistically significant (P < 0.05) reductions in the MICs for all tested drugs, with decreases to azoles being statistically greater than those for amphotericin B and caspofungin (P < 0.05). The molecular analyses showed a genetic similarity among the three tested isolates, suggesting the occurrence of candidemia in the studied animal. These findings highlight the importance of monitoring antifungal susceptibility of Candida spp. from veterinary sources, especially as they may indicate the occurrence of primary azole resistance even in wild animals.

  6. Azole-resistant Candida albicans from a wild Brazilian porcupine (Coendou prehensilis): a sign of an environmental imbalance?

    PubMed

    Castelo-Branco, D S C M; Brilhante, R S N; Paiva, M A N; Teixeira, C E C; Caetano, E P; Ribeiro, J F; Cordeiro, R A; Sidrim, J J C; Monteiro, A J; Rocha, M F G

    2013-07-01

    This study aimed at evaluating the in vitro antifungal susceptibility of Candida albicans isolates obtained during necropsy of a wild Brazilian porcupine and the mechanism of azole resistance. Initially, we investigated the in vitro susceptibility of the three isolates to amphotericin B, caspofungin, fluconazole, itraconazole, ketoconazole and voriconazole. Afterwards, three sub-inhibitory concentrations (47, 21 and 12 mg/l) of promethazine, an efflux pump inhibitor, were tested in combination with the antifungal drugs in order to evaluate the role of these pumps in the development of antifungal resistance. In addition, the three isolates were submitted to RAPD-PCR and M13-fingerprinting analyses. The minimum inhibitory concentrations (MICs) obtained with the isolates were 1, 0.03125, 250, 125, 8 and 250 mg/l for amphotericin B, caspofungin, fluconazole, itraconazole, ketoconazole and voriconazole, respectively, and the isolates were found to be resistant to all tested azoles. The addition of the three subinhibitory concentrations of promethazine resulted in statistically significant (P < 0.05) reductions in the MICs for all tested drugs, with decreases to azoles being statistically greater than those for amphotericin B and caspofungin (P < 0.05). The molecular analyses showed a genetic similarity among the three tested isolates, suggesting the occurrence of candidemia in the studied animal. These findings highlight the importance of monitoring antifungal susceptibility of Candida spp. from veterinary sources, especially as they may indicate the occurrence of primary azole resistance even in wild animals. PMID:23286353

  7. [Activity of ajoene on dermatophytes, Candida albicans and Malassezia furfur.].

    PubMed

    de González, M I; Mendoza, M; Bastardo de Albornoz, M; Apitz-Castro, R

    1998-12-01

    The sensitivity in vitro of an isolate of Trichophyton rubrum and another of Trichophyton mentagrophytes to ajoene. This compound inhibited the growth of both isolates, showing an minimal inhibitory concentration (MIC) of 60 microg/ml and a minimal fungicidal concentration (MFC) of 75 microg/ml. In vivo, the ajoene cream at 0.4% used once a day and every five days in 38 patients (thirty dermatophytosis and eight Candida intertrigo cases) achieved a low percentage of cures (23.3% and 12.5%, respectively). However, an excellent clinic response was obtained in eight patients with pityriasis versicolor, with a cure in 87.5% of the cases.

  8. New tools for phenotypic analysis in Candida albicans: the WAR1 gene confers resistance to sorbate.

    PubMed

    Lebel, Karine; MacPherson, Sarah; Turcotte, Bernard

    2006-03-01

    Availability of the complete sequence of the Candida albicans genome allows for global gene analysis. We designed a gene deletion method to facilitate such studies. First, we constructed C. albicans strains that are both Deltaura3 and Deltatrp1. Second, we designed a system that relies on in vitro recombination, using the Gateway((R)) technology, for efficient generation of deletion cassettes. They are generated in two steps: (a) upstream and downstream DNA fragments of the chromosomal region to be deleted are amplified by PCR and introduced into two separate entry vectors; (b) the second step involves a quadruple recombination event including the two entry vectors, a plasmid bearing a marker of interest and a destination vector, in order to generate a plasmid containing the deletion cassette. The deletion plasmid contains very rare restriction sites for convenient excision of the knockout cassette. Selection in C. albicans can be performed with one of the following markers: the C. albicans URA3 gene, a modified S. cerevisiae TRP1 gene or the mycophenolic acid resistance (MPA(R)) gene. Upon integration into the genome, these markers can be removed by the use of 5-fluoroorotic acid (URA3), 5-fluoroanthranilic acid (TRP1) or the FLP recombinase (MPA(R)). Using this approach, we show that removal of the C. albicans orf19.1035 gene results in sensitivity to the weak acid sorbate, while its overexpression increases resistance to this compound. We named it WAR1, in analogy to its S. cerevisiae orthologue. PMID:16544288

  9. Modeled microgravity increases filamentation, biofilm formation, phenotypic switching, and antimicrobial resistance in Candida albicans.

    PubMed

    Searles, Stephen C; Woolley, Christine M; Petersen, Rachel A; Hyman, Linda E; Nielsen-Preiss, Sheila M

    2011-10-01

    Candida albicans is an opportunistic fungal pathogen responsible for a variety of cutaneous and systemic human infections. Virulence of C. albicans increases upon exposure to some environmental stresses; therefore, we explored phenotypic responses of C. albicans following exposure to the environmental stress of low-shear modeled microgravity. Upon long-term (12-day) exposure to low-shear modeled microgravity, C. albicans transitioned from yeast to filamentous forms at a higher rate than observed under control conditions. Consistently, genes associated with cellular morphology were differentially expressed in a time-dependent manner. Biofilm communities, credited with enhanced resistance to environmental stress, formed in the modeled microgravity bioreactor and had a more complex structure than those formed in control conditions. In addition, cells exposed to low-shear modeled microgravity displayed phenotypic switching, observed as a near complete transition from smooth to "hyper" irregular wrinkle colony morphology. Consistent with the presence of biofilm communities and increased rates of phenotypic switching, cells exposed to modeled microgravity were significantly more resistant to the antifungal agent Amphotericin B. Together, these data indicate that C. albicans adapts to the environmental stress of low-shear modeled microgravity by demonstrating virulence-associated phenotypes.

  10. Inhibitory Effect of Sophorolipid on Candida albicans Biofilm Formation and Hyphal Growth

    PubMed Central

    Haque, Farazul; Alfatah, Md.; Ganesan, K.; Bhattacharyya, Mani Shankar

    2016-01-01

    Candida albicans causes superficial and life-threatening systemic infections. These are difficult to treat often due to drug resistance, particularly because C. albicans biofilms are inherently resistant to most antifungals. Sophorolipid (SL), a glycolipid biosurfactant, has been shown to have antimicrobial and anticancer properties. In this study, we investigated the effect of SL on C. albicans biofilm formation and preformed biofilms. SL was found to inhibit C. albicans biofilm formation as well as reduce the viability of preformed biofilms. Moreover, SL, when used along with amphotericin B (AmB) or fluconazole (FLZ), was found to act synergistically against biofilm formation and preformed biofilms. Effect of SL on C. albicans biofilm formation was further visualized by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM), which revealed absence of hyphae, typical biofilm architecture and alteration in the morphology of biofilm cells. We also found that SL downregulates the expression of hypha specific genes HWP1, ALS1, ALS3, ECE1 and SAP4, which possibly explains the inhibitory effect of SL on hyphae and biofilm formation. PMID:27030404

  11. A comprehensive Candida albicans PeptideAtlas build enables deep proteome coverage.

    PubMed

    Vialas, Vital; Sun, Zhi; Reales-Calderón, Jose A; Hernáez, María L; Casas, Vanessa; Carrascal, Montserrat; Abián, Joaquín; Monteoliva, Lucía; Deutsch, Eric W; Moritz, Robert L; Gil, Concha

    2016-01-10

    To provide new and expanded proteome documentation of the opportunistically pathogen Candida albicans, we have developed new protein extraction and analysis routines to provide a new, extended and enhanced version of the C. albicans PeptideAtlas. Two new datasets, resulting from experiments consisting of exhaustive subcellular fractionations and different growing conditions, plus two additional datasets from previous experiments on the surface and the secreted proteomes, have been incorporated to increase the coverage of the proteome. High resolution precursor mass spectrometry (MS) and ion trap tandem MS spectra were analyzed with three different search engines using a database containing allele-specific sequences. This approach, novel for a large-scale C. albicans proteomics project, was combined with the post-processing and filtering implemented in the Trans Proteomic Pipeline consistently used in the PeptideAtlas project and resulted in 49,372 additional peptides (3-fold increase) and 1630 more proteins (1.6-fold increase) identified in the new C. albicans PeptideAtlas with respect to the previous build. A total of 71,310 peptides and 4174 canonical (minimal non-redundant set) proteins (4115 if one protein per pair of alleles is considered) were identified representing 66% of the 6218 proteins in the predicted proteome. This makes the new PeptideAtlas build the most comprehensive C. albicans proteomics resource available and the only large-scale one with detections of individual alleles. PMID:26493587

  12. Fimbria-mediated adherence of Candida albicans to glycosphingolipid receptors on human buccal epithelial cells.

    PubMed Central

    Yu, L; Lee, K K; Sheth, H B; Lane-Bell, P; Srivastava, G; Hindsgaul, O; Paranchych, W; Hodges, R S; Irvin, R T

    1994-01-01

    Candida albicans is an opportunist fungal pathogen that has the ability to adhere to host cell surface receptors via a number of adhesins. Yu et al. (L. Yu, K. K. Lee, K. Ens, P. C. Doig, M. R. Carpenter, W. Staddon, R. S. Hodges, W. Paranchych, and R. T. Irvin, Infect. Immun. 62:2834-2842, 1994) described the purification and initial characterization of a fimbrial adhesin from C. albicans. In this paper, we show that C. albicans fimbriae also bind to asialo-GM1 [gangliotetraosylceramide: beta Gal(1-3)beta GalNAc(1-4) beta Gal(1-4)beta Glc(1-1)Cer] immobilized on microtiter plates in a saturable and concentration-dependent manner. C. albicans fimbrial binding to exfoliated human buccal epithelial cells (BECs) was inhibited by asialo-GM1 in in vitro binding assays. The fimbriae interact with the glycosphingolipid receptors via the carbohydrate portion of the receptors, since fimbriae were observed to bind to synthetic beta GalNAc(1-4)beta Gal-protein conjugates and the disaccharide was able to inhibit binding of fimbriae to BECs in in vitro binding assays. We conclude from these results that the C. albicans yeast form expresses a fimbrial adhesin that binds to glycosphingolipids displayed on the surface of human BECs. Images PMID:8005674

  13. The transcriptional stress response of Candida albicans to weak organic acids.

    PubMed

    Cottier, Fabien; Tan, Alrina Shin Min; Chen, Jinmiao; Lum, Josephine; Zolezzi, Francesca; Poidinger, Michael; Pavelka, Norman

    2015-04-01

    Candida albicans is the most important fungal pathogen of humans, causing severe infections, especially in nosocomial and immunocompromised settings. However, it is also the most prevalent fungus of the normal human microbiome, where it shares its habitat with hundreds of trillions of other microbial cells. Despite weak organic acids (WOAs) being among the most abundant metabolites produced by bacterial microbiota, little is known about their effect on C. albicans. Here we used a sequencing-based profiling strategy to systematically investigate the transcriptional stress response of C. albicans to lactic, acetic, propionic, and butyric acid at several time points after treatment. Our data reveal a complex transcriptional response, with individual WOAs triggering unique gene expression profiles and with important differences between acute and chronic exposure. Despite these dissimilarities, we found significant overlaps between the gene expression changes induced by each WOA, which led us to uncover a core transcriptional response that was largely unrelated to other previously published C. albicans transcriptional stress responses. Genes commonly up-regulated by WOAs were enriched in several iron transporters, which was associated with an overall decrease in intracellular iron concentrations. Moreover, chronic exposure to any WOA lead to down-regulation of RNA synthesis and ribosome biogenesis genes, which resulted in significant reduction of total RNA levels and of ribosomal RNA in particular. In conclusion, this study suggests that gastrointestinal microbiota might directly influence C. albicans physiology via production of WOAs, with possible implications of how this fungus interacts with its host in both health and disease. PMID:25636313

  14. In vivo role of Candida albicans β-hexosaminidase (HEX1) in carbon scavenging

    PubMed Central

    Ruhela, Deepa; Kamthan, Mohan; Saha, Paramita; Majumdar, Subeer S; Datta, Kasturi; Abdin, Malik Zainul; Datta, Asis

    2015-01-01

    The capability to utilize of N-acetylglucosamine (GlcNAc) as a carbon source is an important virulence attribute of Candida albicans. But there is a lack of information about the in vivo source of GlcNAc for the pathogen within the host environment. Here, we have characterized the GlcNAc-inducible β-hexosaminidase gene (HEX1) of C. albicans showing a role in carbon scavenging. In contrast to earlier studies, we have reported HEX1 to be a nonessential gene as shown by homozygous trisomy test. Virulence study in the systemic mouse murine model showed that Δhex1 strain is significantly less virulent in comparison to the wild-type strain. Moreover, Δhex1 strain also showed a higher susceptibility to peritoneal macrophages. In an attempt to determine possible substrates of Hex1, hyaluronic acid (HA) was treated with purified Hex1 enzyme. A significant release of GlcNAc was observed by gas chromatography-mass spectrometry analysis analysis suggesting HA degradation. Interestingly, immunohistochemistry analysis showed significant accumulation of HA in the mice kidney infected with the wild-type strain of C. albicans. Northern blot analysis showed that C. albicans HEX1 is expressed during mice renal colonization. Thus, C. albicans can obtain GlcNAc during organ colonization by secreting Hex1 via degradation of host HA. PMID:26177944

  15. Human salivary histatin 5 fungicidal action does not induce programmed cell death pathways in Candida albicans.

    PubMed

    Wunder, David; Dong, Jin; Baev, Didi; Edgerton, Mira

    2004-01-01

    Salivary histatins (Hsts) are potent candidacidal proteins that induce a nonlytic form of cell death in Candida albicans accompanied by loss of mean cell volume, cell cycle arrest, and elevation of intracellular levels of reactive oxygen species (ROS). Since these phenotypes are often markers of programmed cell death and apoptosis, we investigated whether other classical markers of apoptosis, including generation of intracellular ROS and protein carbonyl groups, chromosomal fragmentation (laddering), and cytochrome c release, are found in Hst 5-mediated cell death. Increased intracellular levels of ROS in C. albicans were detected in cells both following exogenous application of Hst 5 and following intracellular expression of Hst 5. However, Western blot analysis failed to detect specifically increased protein carbonylation in Hst 5-treated cells. There was no evidence of chromosomal laddering and no cytochrome c release was observed following treatment of C. albicans mitochondria with Hst 5. Superoxide dismutase enzymes of C. albicans and Saccharomyces cerevisiae provide essential protection against oxidative stress; therefore, we tested whether SOD mutants have increased susceptibility to Hst 5, as expected if ROS mediate fungicidal effects. Cell survival of S. cerevisiae SOD1/SOD2 mutants and C. albicans SOD1 mutants following Hst 5 treatment (31 micro M) was indistinguishable from the survival of wild-type cells treated with Hst 5. We conclude that ROS may not play a direct role in fungicidal activity and that Hst 5 does not initiate apoptosis or programmed cell death pathways. PMID:14693527

  16. Endogenous nitric oxide accumulation is involved in the antifungal activity of Shikonin against Candida albicans

    PubMed Central

    Liao, Zebin; Yan, Yu; Dong, Huaihuai; Zhu, Zhenyu; Jiang, Yuanying; Cao, Yingying

    2016-01-01

    The aim of the present study was to investigate the role of nitric oxide (NO) in the antifungal activity of Shikonin (SK) against Candida albicans (C. albicans) and to clarify the underlying mechanism. The results showed that the NO donors S-nitrosoglutathione (GSNO) and L-arginine could enhance the antifungal activity of SK, whereas the NO production inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) attenuated antifungal action. Using the fluorescent dye 3-amino,4-aminomethyl-2′, 7-difluorescein, diacetate (DAF-FM DA), we found that the accumulation of NO in C. albicans was increased markedly by SK in a time- and dose-dependent manner. In addition, the results of real-time reverse transcription-PCR (RT-PCR) demonstrated that the transcription level of YHB1 in C. albicans was greatly increased upon incubation of SK. Consistently, the YHB1-null mutant (yhb1Δ/Δ) exhibited a higher susceptibility to SK than wild-type cells. In addition, although the transcription level of CTA4 in C. albicans was not significantly changed when exposed to SK, the CTA4-null mutant (cta4Δ/Δ) was more susceptible to SK. Collectively, SK is the agent found to execute its antifungal activity directly via endogenous NO accumulation, and NO-mediated damage is related to the suppression of YHB1 and the function of CTA4. PMID:27530748

  17. A novel renal epithelial cell in vitro assay to assess Candida albicans virulence

    PubMed Central

    Szabo, Edina K; MacCallum, Donna M

    2014-01-01

    Candida albicans, an opportunistic fungal pathogen, can cause severe systemic infections in susceptible patient groups. Systemic candidiasis is mainly studied in the mouse intravenous challenge model, where progressive infection correlates with increased early renal chemokine levels. To develop a new in vitro assay to assess C. albicans virulence, which reflects the events occurring in the murine infection model, renal M-1 cortical collecting duct epithelial cells were evaluated as the early producers of cytokines in response to C. albicans. We show that renal epithelial cells respond only to live C. albicans cells capable of forming hyphae, producing chemokines KC and MIP-2, with levels correlating with epithelial cell damage. By assaying epithelial cell responses to strains of known virulence in the murine intravenous challenge model we demonstrate that renal epithelial cells can discriminate between virulent and attenuated strains. This simple, novel assay is a useful initial screen for altered virulence of C. albicans mutants or clinical isolates in vitro and provides an alternative to the mouse systemic infection model. PMID:24225657

  18. Large-Scale Identification of Putative Exported Proteins in Candida albicans by Genetic Selection

    PubMed Central

    Monteoliva, L.; López Matas, M.; Gil, C.; Nombela, C.; Pla, J.

    2002-01-01

    In all living organisms, secreted proteins play essential roles in different processes. Of special interest is the construction of the fungal cell wall, since this structure is absent from mammalian cells. The identification of the proteins involved in its biogenesis is therefore a primary goal in antifungal research. To perform a systematic identification of such proteins in Candida albicans, we carried out a genetic screening in which in-frame fusions with an intracellular allele of invertase gene SUC2 of Saccharomyces cerevisiae can be used to select and identify putatively exported proteins in the heterologous host S. cerevisiae. Eighty-three clones were selected, including 11 previously identified genes from C. albicans as well as 41 C. albicans genes that encode proteins homologous to already described proteins from related organisms. They include enzymes involved in cell wall synthesis and protein secretion. We also found membrane receptors and transporters presumably related to the interaction of C. albicans with the environment as well as extracellular enzymes and proteins involved in different morphological transitions. In addition, 11 C. albicans open reading frames (ORFs) identified in this screening encode proteins homologous to unknown or putative proteins, while 5 ORFs encode novel secreted proteins without known homologues in other organisms. This screening procedure therefore not only identifies a set of targets of interest in antifungal research but also provides new clues for understanding the topological locations of many proteins involved in processes relevant to the pathogenicity of this microorganism. PMID:12456000

  19. A comprehensive Candida albicans PeptideAtlas build enables deep proteome coverage.

    PubMed

    Vialas, Vital; Sun, Zhi; Reales-Calderón, Jose A; Hernáez, María L; Casas, Vanessa; Carrascal, Montserrat; Abián, Joaquín; Monteoliva, Lucía; Deutsch, Eric W; Moritz, Robert L; Gil, Concha

    2016-01-10

    To provide new and expanded proteome documentation of the opportunistically pathogen Candida albicans, we have developed new protein extraction and analysis routines to provide a new, extended and enhanced version of the C. albicans PeptideAtlas. Two new datasets, resulting from experiments consisting of exhaustive subcellular fractionations and different growing conditions, plus two additional datasets from previous experiments on the surface and the secreted proteomes, have been incorporated to increase the coverage of the proteome. High resolution precursor mass spectrometry (MS) and ion trap tandem MS spectra were analyzed with three different search engines using a database containing allele-specific sequences. This approach, novel for a large-scale C. albicans proteomics project, was combined with the post-processing and filtering implemented in the Trans Proteomic Pipeline consistently used in the PeptideAtlas project and resulted in 49,372 additional peptides (3-fold increase) and 1630 more proteins (1.6-fold increase) identified in the new C. albicans PeptideAtlas with respect to the previous build. A total of 71,310 peptides and 4174 canonical (minimal non-redundant set) proteins (4115 if one protein per pair of alleles is considered) were identified representing 66% of the 6218 proteins in the predicted proteome. This makes the new PeptideAtlas build the most comprehensive C. albicans proteomics resource available and the only large-scale one with detections of individual alleles.

  20. Potent Activities of Roemerine against Candida albicans and the Underlying Mechanisms.

    PubMed

    Ma, Chaoyu; Du, Faya; Yan, Lan; He, Gonghao; He, Jianchang; Wang, Chengying; Rao, Gaoxiong; Jiang, Yuanying; Xu, Guili

    2015-01-01

    Roemerine (RM) is an aporphine alkaloid isolated from the fresh rattan stem of Fibraurea recisa, and it has been demonstrated to have certain antifungal activity. This study aimed to investigate the antifungal activity of RM and the underlying mechanisms in Candida albicans (C. albicans). The in vitro antifungal activity of RM was evaluated by a series of experiments, including the XTT reduction assay, confocal laser scanning microscopy assay, scanning electron microscope assay. Results showed that 1 μg/mL RM inhibited biofilm formation significantly (p < 0.01) both in Spider medium and Lee's medium. In addition, RM could inhibit yeast-to-hyphae transition of C. albicans in a dose-dependent manner. The biofilm-specific and hypha-specific genes such as YWP1, SAP5, SAP6, HWP1, ECE1 were up-regulated and EFG1 was down-regulated after 8 μg/mL RM treatment. Furthermore, the toxicity of RM was investigated using C. elegans worms, three cancer cells and one normal cell. The date showed that RM had no significant toxicity. In conclusion, RM could inhibited the formation of C. albicans biofilm in vitro, but it had no fungicidal effect on planktonic C. albicans cells, and the anti-biofilm mechanism may be related to the cAMP pathway.

  1. The GRF10 homeobox gene regulates filamentous growth in the human fungal pathogen Candida albicans.

    PubMed

    Ghosh, Anup K; Wangsanut, Tanaporn; Fonzi, William A; Rolfes, Ronda J

    2015-12-01

    Candida albicans is the most common human fungal pathogen and can cause life-threatening infections. Filamentous growth is critical in the pathogenicity of C. albicans, as the transition from yeast to hyphal forms is linked to virulence and is also a pivotal process in fungal biofilm development. Homeodomain-containing transcription factors have been linked to developmental processes in fungi and other eukaryotes. We report here on GRF10, a homeobox transcription factor-encoding gene that plays a role in C. albicans filamentation. Deletion of the GRF10 gene, in both C. albicans SN152 and BWP17 strain backgrounds, results in mutants with strongly decreased hyphal growth. The mutants are defective in chlamydospore and biofilm formation, as well as showing dramatically attenuated virulence in a mouse infection model. Expression of the GRF10 gene is highly induced during stationary phase and filamentation. In summary, our study emphasizes a new role for the homeodomain-containing transcription factor in morphogenesis and pathogenicity of C. albicans.

  2. Stimulation of superoxide production increases fungicidal action of miconazole against Candida albicans biofilms

    PubMed Central

    De Cremer, Kaat; De Brucker, Katrijn; Staes, Ines; Peeters, Annelies; Van den Driessche, Freija; Coenye, Tom; Cammue, Bruno P. A.; Thevissen, Karin

    2016-01-01

    We performed a whole-transcriptome analysis of miconazole-treated Candida albicans biofilms, using RNA-sequencing. Our aim was to identify molecular pathways employed by biofilm cells of this pathogen to resist action of the commonly used antifungal miconazole. As expected, genes involved in sterol biosynthesis and genes encoding drug efflux pumps were highly induced in biofilm cells upon miconazole treatment. Other processes were affected as well, including the electron transport chain (ETC), of which eight components were transcriptionally downregulated. Within a diverse set of 17 inhibitors/inducers of the transcriptionally affected pathways, the ETC inhibitors acted most synergistically with miconazole against C. albicans biofilm cells. Synergy was not observed for planktonically growing C. albicans cultures or when biofilms were treated in oxygen-deprived conditions, pointing to a biofilm-specific oxygen-dependent tolerance mechanism. In line, a correlation between miconazole’s fungicidal action against C. albicans biofilm cells and the levels of superoxide radicals was observed, and confirmed both genetically and pharmacologically using a triple superoxide dismutase mutant and a superoxide dismutase inhibitor N-N′-diethyldithiocarbamate, respectively. Consequently, ETC inhibitors that result in mitochondrial dysfunction and affect production of reactive oxygen species can increase miconazole’s fungicidal activity against C. albicans biofilm cells. PMID:27272719

  3. Nuclear fusion occurs during mating in Candida albicans and is dependent on the KAR3 gene.

    PubMed

    Bennett, Richard J; Miller, Mathew G; Chua, Penelope R; Maxon, Mary E; Johnson, Alexander D

    2005-02-01

    It is now well established that mating can occur between diploid a and alpha cells of Candida albicans. There is, however, controversy over when, and with what efficiency, nuclear fusion follows cell fusion to create stable tetraploid a/alpha cells. In this study, we have analysed the mating process between C. albicans strains using both cytological and genetic approaches. Using strains derived from SC5314, we used a number of techniques, including time-lapse microscopy, to demonstrate that efficient nuclear fusion occurs in the zygote before formation of the first daughter cell. Consistent with these observations, zygotes micromanipulated from mating mixes gave rise to mononuclear tetraploid cells, even when no selection for successful mating was applied to them. Mating between different clinical isolates of C. albicans revealed that while all isolates could undergo nuclear fusion, the efficiency of nuclear fusion varied in different crosses. We also show that nuclear fusion in C. albicans requires the Kar3 microtubule motor protein. Deletion of the CaKAR3 gene from both mating partners had little or no effect on zygote formation but reduced the formation of stable tetraploids more than 600-fold, as determined by quantitative mating assays. These findings demonstrate that nuclear fusion is an active process that can occur in C. albicans at high frequency to produce stable, mononucleate mating products.

  4. Potent Activities of Roemerine against Candida albicans and the Underlying Mechanisms.

    PubMed

    Ma, Chaoyu; Du, Faya; Yan, Lan; He, Gonghao; He, Jianchang; Wang, Chengying; Rao, Gaoxiong; Jiang, Yuanying; Xu, Guili

    2015-01-01

    Roemerine (RM) is an aporphine alkaloid isolated from the fresh rattan stem of Fibraurea recisa, and it has been demonstrated to have certain antifungal activity. This study aimed to investigate the antifungal activity of RM and the underlying mechanisms in Candida albicans (C. albicans). The in vitro antifungal activity of RM was evaluated by a series of experiments, including the XTT reduction assay, confocal laser scanning microscopy assay, scanning electron microscope assay. Results showed that 1 μg/mL RM inhibited biofilm formation significantly (p < 0.01) both in Spider medium and Lee's medium. In addition, RM could inhibit yeast-to-hyphae transition of C. albicans in a dose-dependent manner. The biofilm-specific and hypha-specific genes such as YWP1, SAP5, SAP6, HWP1, ECE1 were up-regulated and EFG1 was down-regulated after 8 μg/mL RM treatment. Furthermore, the toxicity of RM was investigated using C. elegans worms, three cancer cells and one normal cell. The date showed that RM had no significant toxicity. In conclusion, RM could inhibited the formation of C. albicans biofilm in vitro, but it had no fungicidal effect on planktonic C. albicans cells, and the anti-biofilm mechanism may be related to the cAMP pathway. PMID:26426004

  5. Quorum Sensing in the Dimorphic Fungus Candida albicans Is Mediated by Farnesol

    PubMed Central

    Hornby, Jacob M.; Jensen, Ellen C.; Lisec, Amber D.; Tasto, Joseph J.; Jahnke, Brandon; Shoemaker, Richard; Dussault, Patrick; Nickerson, Kenneth W.

    2001-01-01

    The inoculum size effect in the dimorphic fungus Candida albicans results from production of an extracellular quorum-sensing molecule (QSM). This molecule prevents mycelial development in both a growth morphology assay and a differentiation assay using three chemically distinct triggers for germ tube formation (GTF): l-proline, N-acetylglucosamine, and serum (either pig or fetal bovine). In all cases, the presence of QSM prevents the yeast-to-mycelium conversion, resulting in actively budding yeasts without influencing cellular growth rates. QSM exhibits general cross-reactivity within C. albicans in that supernatants from strain A72 are active on five other strains of C. albicans and vice versa. The QSM excreted by C. albicans is farnesol (C15H26O; molecular weight, 222.37). QSM is extracellular, and is produced continuously during growth and over a temperature range from 23 to 43°C, in amounts roughly proportional to the CFU/milliliter. Production is not dependent on the type of carbon source nor nitrogen source or on the chemical nature of the growth medium. Both commercial mixed isomer and (E,E)-farnesol exhibited QSM activity (the ability to prevent GTF) at a level sufficient to account for all the QSM activity present in C. albicans supernatants, i.e., 50% GTF at ca. 30 to 35 μM. Nerolidol was ca. two times less active than farnesol. Neither geraniol (C10), geranylgeraniol (C20), nor farnesyl pyrophosphate had any QSM activity. PMID:11425711

  6. Microsatellite-based genotyping of Candida albicans isolated from patients with superficial candidiasis.

    PubMed

    Shimizu, Kazue; Hattori, Hisao; Adachi, Hidesada; Oshima, Ryosuke; Horii, Toshinobu; Tanaka, Reiko; Yaguchi, Takashi; Tomita, Yasushi; Akiyama, Masashi; Kawamoto, Fumihiko; Kanbe, Toshio

    2011-01-01

    This study aimed to examine the genotype distribution of Candida albicans and the major genotypes involved in superficial candidiasis. The genotypes of C. albicans isolated from the infection sites of patients with superficial candidiasis (referred to as infection isolates) were analyzed by fragment analysis using 4 microsatellite markers (HIS3, CDC3, CAI and CAIII). Genotypes of the infection isolates were compared with those of C. albicans isolated from oral mucosa of non-candidiasis patients (referred to as oral isolates). Isolates of C. albicans showed 4 major genotypes for HIS3/CAI (" a " for 148 : 148 / 23 : 23," b " for 148 : 160 / 33 : 41," c " for 148 : 164 / 32 : 41 and " d " for 152 : 152 / 18 : 27). The genotypes " a "," b " and " d " were commonly found in oral (4.7, 8.8 and 7.6%, respectively) and infection (6.6, 9.2 and 15.4%, respectively) isolates. No isolates of genotype " c " were isolated from infection sites. The genotype " a " was found in the isolates from patients with genitalia candidiasis. Genotyping of multiple isolates from an individual patient showed that C. albicans from infection sites was genetically homogenous as compared with that of oral isolates, even in the same patient with candidiasis.

  7. Transcriptomics Analysis of Candida albicans Treated with Huanglian Jiedu Decoction Using RNA-seq

    PubMed Central

    Yang, Qianqian; Gao, Lei; Tao, Maocan; Chen, Zhe; Yang, Xiaohong; Cao, Yi

    2016-01-01

    Candida albicans is the major invasive fungal pathogen of humans, causing diseases ranging from superficial mucosal infections to disseminated, systemic infections that are often life-threatening. Resistance of C. albicans to antifungal agents and limited antifungal agents has potentially serious implications for management of infections. As a famous multiherb prescription in China, Huanglian Jiedu Decoction (HLJJD, Orengedokuto in Japan) is efficient against Trichophyton mentagrophytes and C. albicans. But the antifungal mechanism of HLJDD remains unclear. In this study, by using RNA-seq technique, we performed a transcriptomics analysis of gene expression changes for C. albicans under the treatment of HLJDD. A total of 6057 predicted protein-encoding genes were identified. By gene expression analysis, we obtained a total of 735 differentially expressed genes (DEGs), including 700 upregulated genes and 35 downregulated genes. Genes encoding multidrug transporters such as ABC transporter and MFS transporter were identified to be significantly upregulated. Meanwhile, by pathway enrichment analysis, we identified 26 significant pathways, in which pathways of DNA replication and transporter activity were mainly involved. These results might provide insights for the inhibition mechanism of HLJDD against C. albicans. PMID:27143984

  8. Cloning and characterization of the plasma membrane H(+)-ATPase from Candida albicans.

    PubMed Central

    Monk, B C; Kurtz, M B; Marrinan, J A; Perlin, D S

    1991-01-01

    The Candida albicans PMA1 gene was isolated from a genomic library by using a hybridization probe obtained from the PMA1 gene of Saccharomyces cerevisiae. The gene was localized to chromosome III of the Candida genome. An open reading frame of 2,685 nucleotides predicts an amino acid sequence of 895 amino acids that is 83% homologous at both the DNA and protein levels to its S. cerevisiae equivalent. A polyadenylated mRNA transcript of about 4,000 nucleotides contains a highly folded AU-rich leader of 242 nucleotides. The structure of the gene, codon bias, and levels of approximately 100-kDa H(+)-ATPase protein recovered in plasma membranes indicate a highly expressed gene. The plasma membrane ATPase was purified to about 90% homogeneity and appeared to be blocked at the amino terminus. Three hydrophobic membrane sector tryptic fragments from the partially digested ATPase provided internal sequence information for over 50 amino acids, which agrees with the sequence predicted by the cloned gene. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the C. albicans enzyme is about 3 kDa smaller than its Saccharomyces counterpart and was consistent with a predicted Mr of 97,398. Antibodies to the S. cerevisiae whole ATPase or its carboxyl terminus bound to the C. albicans enzyme but with lower avidity. Kinetic analysis showed that the Candida and Saccharomyces ATPases respond to glucose activation-starvation in nonidentical fashions. The amino-terminal domain of the C. albicans ATPase is marked by a net deletion of 23 amino acids in comparison with the S. cerevisiae ATPase. These differences maintain net charge, occur in nonconserved regions of fungal ATPases, and are sufficient to account for the observed difference in electrophoretic mobility between the two yeast ATPases. Images FIG. 3 FIG. 4 FIG. 5 FIG. 6 FIG. 7 PMID:1834633

  9. Candida albicans in Multispecies Oral Communities; A Keystone Commensal?

    PubMed

    Janus, Marleen M; Willems, Hubertine M E; Krom, Bastiaan P

    2016-01-01

    The complexity of the oral cavity, in which many hundreds of microbial species interact represents a challenge for modern microbiologists. What are all these species doing there? And why do we accept so many opportunistic pathogens to be part of our health (commensal) microflora? While the role of bacteria are often being studied, the role of fungi in the interactions within the oral cavity are understudied. This is partly because fungi in the oral cavity are generally considered as pathogens and related to diseases. In this chapter we will explore mechanisms of interaction between bacteria and fungi in the oral cavity that are involved in maintenance of oral health. We will argue that fungi in general and C. albicans specifically, should be regarded a keystone commensal in the oral cavity. PMID:27271681

  10. Flavodoxin-Like Proteins Protect Candida albicans from Oxidative Stress and Promote Virulence.

    PubMed

    Li, Lifang; Naseem, Shamoon; Sharma, Sahil; Konopka, James B

    2015-09-01

    The fungal pathogen Candida albicans causes lethal systemic infections in humans. To better define how pathogens resist oxidative attack by the immune system, we examined a family of four Flavodoxin-Like Proteins (FLPs) in C. albicans. In agreement with previous studies showing that FLPs in bacteria and plants act as NAD(P)H quinone oxidoreductases, a C. albicans quadruple mutant lacking all four FLPs (pst1Δ, pst2Δ, pst3Δ, ycp4Δ) was more sensitive to benzoquinone. Interestingly, the quadruple mutant was also more sensitive to a variety of oxidants. Quinone reductase activity confers important antioxidant effects because resistance to oxidation was restored in the quadruple mutant by expressing either Escherichia coli wrbA or mammalian NQO1, two distinct types of quinone reductases. FLPs were detected at the plasma membrane in C. albicans, and the quadruple mutant was more sensitive to linolenic acid, a polyunsaturated fatty acid that can auto-oxidize and promote lipid peroxidation. These observations suggested that FLPs reduce ubiquinone (coenzyme Q), enabling it to serve as an antioxidant in the membrane. In support of this, a C. albicans coq3Δ mutant that fails to synthesize ubiquinone was also highly sensitive to oxidative stress. FLPs are critical for survival in the host, as the quadruple mutant was avirulent in a mouse model of systemic candidiasis under conditions where infection with wild type C. albicans was lethal. The quadruple mutant cells initially grew well in kidneys, the major site of C. albicans growth in mice, but then declined after the influx of neutrophils and by day 4 post-infection 33% of the mice cleared the infection. Thus, FLPs and ubiquinone are important new antioxidant mechanisms that are critical for fungal virulence. The potential of FLPs as novel targets for antifungal therapy is further underscored by their absence in mammalian cells. PMID:26325183

  11. Assessing the potential of four cathelicidins for the management of mouse candidiasis and Candida albicans biofilms.

    PubMed

    Yu, Haining; Liu, Xuelian; Wang, Chen; Qiao, Xue; Wu, Sijin; Wang, Hui; Feng, Lan; Wang, Yipeng

    2016-02-01

    As the most common fungal pathogen of humans, severe drug resistance has emerged in the clinically isolated Candida albicans, which lead to the urgency to develop novel antifungal agents. Here, four our previously characterized cathelicidins (cathelicidin-BF, Pc-CATH1, Cc-CATH2, Cc-CATH3) were selected and their antifungal activities against C. albicans were evaluated in vitro and in vivo using amphotericin B and LL-37 as control. Results showed that all four cathelicidins could eradicate standard and clinically isolated C. albicans strains with most MIC values ranging from 1 to 16 μg/ml, in less than 0.5 h revealed by time-kill kinetic assay. Four peptides only exhibited slight hemolytic activity with most HC50 > 200 μg/ml, and retained potent anti-C. albicans activity at salt concentrations below and beyond physiological level. In animal experiment, 50 mg/kg administration of the four cathelicidins could significantly reduce the fungal counts in a murine oral candidiasis model induced by clinically isolated C. albicans. The antibiofilm activity of cathelicidin-BF, the most potent among the five peptides was evaluated, and result showed that cathelicidin-BF strongly inhibited C. albicans biofilm formation at 20 μg/ml. Furthermore, cathelicidin-BF also exhibited potent anti-C. albicans activity in established biofilms as measured by metabolic and fluorescent viability assays. Structure-function analyses suggest that they mainly adopt an α-helical conformations, which enable them to act as a membrane-active molecule. Altogether, the four cathelicidins display great potential for antifungal agent development against candidiasis. PMID:26656137

  12. Anticandidal Effect and Mechanisms of Monoterpenoid, Perillyl Alcohol against Candida albicans.

    PubMed

    Ansari, Moiz A; Fatima, Zeeshan; Hameed, Saif

    2016-01-01

    This study explored the antifungal potential of perillyl alcohol (PA), a natural monoterpene alcohol, against most prevalent human fungal pathogen C. albicans, its clinical isolates and four non-albicans species of Candida. To resolve the potential mechanisms, we used whole genome transcriptome analyses of PA treated Candida cells to examine the affected cellular circuitry of this pathogen. The transcriptome data revealed a link between calcineurin signaling and PA as among the several categories of PA responsive genes the down regulation of calcineurin signaling gene CNB1 was noteworthy which was also confirmed by both molecular docking and susceptibility assays. We observed that PA treated Candida phenocopied compromised calcineurin pathway stress responses and turned sensitive to alkaline pH, ionic, membrane, salinity, endoplasmic reticulum and serum stresses. Indispensability of functional calcineurin was further confirmed as calcineurin mutant was hypersensitive to PA while constitutively expressed calcineurin strain remained resistant. We explored that PA leads to perturbed membrane integrity as depicted through depleted ergosterol levels and disrupted pH homeostasis. Moreover, PA caused cell wall damage which was evident from hypersensitivity against cell wall perturbing agents (congo red, calcoflour white), SEM and enhanced rate of cell sedimentation. Furthermore, PA inhibited potential virulence traits including morphological transition, biofilm formation and displayed diminished capacity to adhere both to the polystyrene surface and buccal epithelial cells. The study also revealed that PA leads to cell cycle arrest and mitochondrial dysfunction in C. albicans. Together, the present study provides enough evidence for further work on PA so that better strategies could be employed to treat Candida infections. PMID:27627759

  13. Anticandidal Effect and Mechanisms of Monoterpenoid, Perillyl Alcohol against Candida albicans

    PubMed Central

    Ansari, Moiz A.; Fatima, Zeeshan; Hameed, Saif

    2016-01-01

    This study explored the antifungal potential of perillyl alcohol (PA), a natural monoterpene alcohol, against most prevalent human fungal pathogen C. albicans, its clinical isolates and four non-albicans species of Candida. To resolve the potential mechanisms, we used whole genome transcriptome analyses of PA treated Candida cells to examine the affected cellular circuitry of this pathogen. The transcriptome data revealed a link between calcineurin signaling and PA as among the several categories of PA responsive genes the down regulation of calcineurin signaling gene CNB1 was noteworthy which was also confirmed by both molecular docking and susceptibility assays. We observed that PA treated Candida phenocopied compromised calcineurin pathway stress responses and turned sensitive to alkaline pH, ionic, membrane, salinity, endoplasmic reticulum and serum stresses. Indispensability of functional calcineurin was further confirmed as calcineurin mutant was hypersensitive to PA while constitutively expressed calcineurin strain remained resistant. We explored that PA leads to perturbed membrane integrity as depicted through depleted ergosterol levels and disrupted pH homeostasis. Moreover, PA caused cell wall damage which was evident from hypersensitivity against cell wall perturbing agents (congo red, calcoflour white), SEM and enhanced rate of cell sedimentation. Furthermore, PA inhibited potential virulence traits including morphological transition, biofilm formation and displayed diminished capacity to adhere both to the polystyrene surface and buccal epithelial cells. The study also revealed that PA leads to cell cycle arrest and mitochondrial dysfunction in C. albicans. Together, the present study provides enough evidence for further work on PA so that better strategies could be employed to treat Candida infections. PMID:27627759

  14. Fungicidal activity of fluconazole against Candida albicans in a synthetic vagina-simulative medium.

    PubMed

    Moosa, Mahomed-Yunus S; Sobel, Jack D; Elhalis, Hussain; Du, Wenjin; Akins, Robert A

    2004-01-01

    Fluconazole (FLZ) has emerged as a highly successful agent in the management of systemic infections of Candida. Cure rates for symptomatic candidiasis following single 150-mg FLZ dose therapy exceed 90%. In vitro, however, FLZ is fungistatic only in a narrow pH range and is not effective at vaginal pH, 4.2. This study evaluated the effect of FLZ on Candida albicans under in vitro conditions resembling the vaginal microenvironment, using vagina-simulative medium (VS). We found that FLZ was fungicidal for C. albicans in VS, but not in other media at the same pH, 4.2. In VS, FLZ was fungicidal at concentrations of >/=8 micro g/ml and reduced viability by greater than 99.9%. Analysis of the components of VS indicated that 17 mM acetic acid, a concentration achieved in the vagina, was responsible for the synergistic, fungicidal effect. This effect was not seen at neutral pH. Other substrates were not effective substitutes for acetic acid; however, short-chained carboxylic acids, glyoxylate and malonate, were effective. Most strains of C. albicans that were resistant to FLZ under standard conditions were killed by FLZ plus acetate. Other species of Candida were also killed, except C. krusei and C. glabrata. This study shows that FLZ has fungicidal activity for Candida species under in vitro conditions that mimic the vaginal microenvironment. This raises the possibility that FLZ may also have fungicidal effects during treatment of vaginal candidiasis. Elucidating the mechanism by which FLZ and acetate interact may disclose vulnerable pathways that could be exploited in drug development. PMID:14693534

  15. Inhibition on Candida albicans biofilm formation using divalent cation chelators (EDTA).

    PubMed

    Ramage, Gordon; Wickes, Brian L; López-Ribot, José L

    2007-12-01

    Candida albicans can readily form biofilms on both inanimate and biological surfaces. In this study we investigated a means of inhibiting biofilm formation using EDTA (Ethylenediaminetetra-acetic acid), a divalent cation chelating agent, which has been shown to affect C. albicans filamentation. Candida albicans biofilms were formed in 96-well microtitre plates. Cells were allowed to adhere for 1, 2, and 4 h at 37 degrees C, washed in PBS, and then treated with different concentrations of EDTA (0, 2.5, 25, and 250 mM). EDTA was also added to the standardized suspension prior to adding to the microtiter plate and to a preformed 24 h biofilm. All plates were then incubated at 37 degrees C for an additional 24 h to allow for biofilm formation. The extent and characteristics of biofilm formation were then microscopically assessed and with a semi-quantitative colorimetric technique based on the use of an XTT-reduction assay. Northern blot analysis of the hyphal wall protein (HWP1) expression was also monitored in planktonic and biofilm cells treated with EDTA. Microscopic analysis and colorimetric readings revealed that filamentation and biofilm formation were inhibited by EDTA in a concentration dependent manner. However, preformed biofilms were minimally affected by EDTA (maximum of 31% reduction at 250 mM). The HWP1 gene expression was reduced in EDTA-treated planktonic and biofilm samples. These results indicate that EDTA inhibits C. albicans biofilm formation are most likely through its inhibitory effect on filamentation and indicates the potential therapeutic effects of EDTA. This compound may serve a non-toxic means of preventing biofilm formation on infections with a C. albicans biofilm etiology. PMID:17909983

  16. Quinacrine inhibits Candida albicans growth and filamentation at neutral pH.

    PubMed

    Kulkarny, Vibhati V; Chavez-Dozal, Alba; Rane, Hallie S; Jahng, Maximillian; Bernardo, Stella M; Parra, Karlett J; Lee, Samuel A

    2014-12-01

    Candida albicans is a common cause of catheter-related bloodstream infections (CR-BSI), in part due to its strong propensity to form biofilms. Drug repurposing is an approach that might identify agents that are able to overcome antifungal drug resistance within biofilms. Quinacrine (QNC) is clinically active against the eukaryotic protozoan parasites Plasmodium and Giardia. We sought to investigate the antifungal activity of QNC against C. albicans biofilms. C. albicans biofilms were incubated with QNC at serially increasing concentrations (4 to 2,048 μg/ml) and assessed using a 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay in a static microplate model. Combinations of QNC and standard antifungals were assayed using biofilm checkerboard analyses. To define a mechanism of action, QNC was assessed for the inhibition of filamentation, effects on endocytosis, and pH-dependent activity. High-dose QNC was effective for the prevention and treatment of C. albicans biofilms in vitro. QNC with fluconazole had no interaction, while the combination of QNC and either caspofungin or amphotericin B demonstrated synergy. QNC was most active against planktonic growth at alkaline pH. QNC dramatically inhibited filamentation. QNC accumulated within vacuoles as expected and caused defects in endocytosis. A tetracycline-regulated VMA3 mutant lacking vacuolar ATPase (V-ATPase) function demonstrated increased susceptibility to QNC. These experiments indicate that QNC is active against C. albicans growth in a pH-dependent manner. Although QNC activity is not biofilm specific, QNC is effective in the prevention and treatment of biofilms. QNC antibiofilm activity likely occurs via several independent mechanisms: vacuolar alkalinization, inhibition of endocytosis, and impaired filamentation. Further investigation of QNC for the treatment and prevention of biofilm-related Candida CR-BSI is warranted. PMID:25288082

  17. Candida albicans Gene Deletion with a Transient CRISPR-Cas9 System.

    PubMed

    Min, Kyunghun; Ichikawa, Yuichi; Woolford, Carol A; Mitchell, Aaron P

    2016-01-01

    Clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated gene 9 (CRISPR-Cas9) systems are used for a wide array of genome-editing applications in organisms ranging from fungi to plants and animals. Recently, a CRISPR-Cas9 system has been developed for the diploid fungal pathogen Candida albicans; the system accelerates genetic manipulation dramatically [V. K. Vyas, M. I. Barrasa, and G. R. Fink, Sci Adv 1(3):e1500248, 2015, http://dx.doi.org/10.1126/sciadv.1500248]. We show here that the CRISPR-Cas9 genetic elements can function transiently, without stable integration into the genome, to enable the introduction of a gene deletion construct. We describe a transient CRISPR-Cas9 system for efficient gene deletion in C. albicans. Our observations suggest that there are two mechanisms that lead to homozygous deletions: (i) independent recombination of transforming DNA into each allele and (ii) recombination of transforming DNA into one allele, followed by gene conversion of the second allele. Our approach will streamline gene function analysis in C. albicans, and our results indicate that DNA can function transiently after transformation of this organism. IMPORTANCE The fungus Candida albicans is a major pathogen. Genetic analysis of this organism has revealed determinants of pathogenicity, drug resistance, and other unique biological features, as well as the identities of prospective drug targets. The creation of targeted mutations has been greatly accelerated recently through the implementation of CRISPR genome-editing technology by Vyas et al. [Sci Adv 1(3):e1500248, 2015, http://dx.doi.org/10.1126/sciadv.1500248]. In this study, we find that CRISPR elements can be expressed from genes that are present only transiently, and we develop a transient CRISPR system that further accelerates C. albicans genetic manipulation.

  18. Candida albicans Gene Deletion with a Transient CRISPR-Cas9 System.

    PubMed

    Min, Kyunghun; Ichikawa, Yuichi; Woolford, Carol A; Mitchell, Aaron P

    2016-01-01

    Clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated gene 9 (CRISPR-Cas9) systems are used for a wide array of genome-editing applications in organisms ranging from fungi to plants and animals. Recently, a CRISPR-Cas9 system has been developed for the diploid fungal pathogen Candida albicans; the system accelerates genetic manipulation dramatically [V. K. Vyas, M. I. Barrasa, and G. R. Fink, Sci Adv 1(3):e1500248, 2015, http://dx.doi.org/10.1126/sciadv.1500248]. We show here that the CRISPR-Cas9 genetic elements can function transiently, without stable integration into the genome, to enable the introduction of a gene deletion construct. We describe a transient CRISPR-Cas9 system for efficient gene deletion in C. albicans. Our observations suggest that there are two mechanisms that lead to homozygous deletions: (i) independent recombination of transforming DNA into each allele and (ii) recombination of transforming DNA into one allele, followed by gene conversion of the second allele. Our approach will streamline gene function analysis in C. albicans, and our results indicate that DNA can function transiently after transformation of this organism. IMPORTANCE The fungus Candida albicans is a major pathogen. Genetic analysis of this organism has revealed determinants of pathogenicity, drug resistance, and other unique biological features, as well as the identities of prospective drug targets. The creation of targeted mutations has been greatly accelerated recently through the implementation of CRISPR genome-editing technology by Vyas et al. [Sci Adv 1(3):e1500248, 2015, http://dx.doi.org/10.1126/sciadv.1500248]. In this study, we find that CRISPR elements can be expressed from genes that are present only transiently, and we develop a transient CRISPR system that further accelerates C. albicans genetic manipulation. PMID:27340698

  19. Telomeric ORFs (TLOs) in Candida spp. Encode Mediator Subunits That Regulate Distinct Virulence Traits

    PubMed Central

    Hokamp, Karsten; Yeomans, Tim; Liu, Zhongle; Church, Michael; Fleming, Alastair B.; Anderson, Matthew Z.; Berman, Judith; Myers, Lawrence C.; Sullivan, Derek J.; Moran, Gary P.

    2014-01-01

    The TLO genes are a family of telomere-associated ORFs in the fungal pathogens Candida albicans and C. dubliniensis that encode a subunit of the Mediator complex with homology to Med2. The more virulent pathogen C. albicans has 15 copies of the gene whereas the less pathogenic species C. dubliniensis has only two (CdTLO1 and CdTLO2). In this study we used C. dubliniensis as a model to investigate the role of TLO genes in regulating virulence and also to determine whether TLO paralogs have evolved to regulate distinct functions. A C. dubliniensis tlo1Δ/tlo2Δ mutant is unable to form true hyphae, has longer doubling times in galactose broth, is more susceptible to oxidative stress and forms increased levels of biofilm. Transcript profiling of the tlo1Δ/tlo2Δ mutant revealed increased expression of starvation responses in rich medium and retarded expression of hypha-induced transcripts in serum. ChIP studies indicated that Tlo1 binds to many ORFs including genes that exhibit high and low expression levels under the conditions analyzed. The altered expression of these genes in the tlo1Δ/tlo2Δ null mutant indicates roles for Tlo proteins in transcriptional activation and repression. Complementation of the tlo1Δ/tlo2Δ mutant with TLO1, but not TLO2, restored wild-type filamentous growth, whereas only TLO2 fully suppressed biofilm growth. Complementation with TLO1 also had a greater effect on doubling times in galactose broth. The different abilities of TLO1 and TLO2 to restore wild-type functions was supported by transcript profiling studies that showed that only TLO1 restored expression of hypha-specific genes (UME6, SOD5) and galactose utilisation genes (GAL1 and GAL10), whereas TLO2 restored repression of starvation-induced gene transcription. Thus, Tlo/Med2 paralogs encoding Mediator subunits regulate different virulence properties in Candida spp. and their expansion may account for the increased adaptability of C. albicans relative to other Candida species

  20. Candida albicans and Pseudomonas aeruginosa Interaction, with Focus on the Role of Eicosanoids

    PubMed Central

    Fourie, Ruan; Ells, Ruan; Swart, Chantel W.; Sebolai, Olihile M.; Albertyn, Jacobus; Pohl, Carolina H.

    2016-01-01

    Candida albicans is commonly found in mixed infections with Pseudomonas aeruginosa, especially in the lungs of cystic fibrosis (CF) patients. Both of these opportunistic pathogens are able to form resistant biofilms and frequently infect immunocompromised individuals. The interaction between these two pathogens, which includes physical interaction as well as secreted factors, is mainly antagonistic. In addition, research suggests considerable interaction with their host, especially with immunomodulatory lipid mediators, termed eicosanoids. Candida albicans and Pseudomonas aeruginosa are both able to utilize arachidonic acid (AA), liberated from the host cells during infection, to form eicosanoids. The production of these eicosanoids, such as Prostaglandin E2, by the host and the pathogens may affect the dynamics of polymicrobial infection and the outcome of infections. It is of considerable importance to elucidate the role of host-produced, as well as pathogen-produced eicosanoids in polymicrobial infection. This review will focus on in vitro as well as in vivo interaction between C. albicans and P. aeruginosa, paying special attention to the role of eicosanoids in the cross-talk between host and the pathogens. PMID:26955357

  1. Co-occurence of filamentation defects and impaired biofilms in Candida albicans protein kinase mutants.

    PubMed

    Konstantinidou, Nina; Morrissey, John Patrick

    2015-12-01

    Pathogenicity of Candida albicans is linked with its developmental stages, notably the capacity switch from yeast-like to hyphal growth, and to form biofilms on surfaces. To better understand the cellular processes involved in C. albicans development, a collection of 63 C. albicans protein kinase mutants was screened for biofilm formation in a microtitre plate assay. Thirty-eight mutants displayed some degree of biofilm impairment, with 20 categorised as poor biofilm formers. All the poor biofilm formers were also defective in the switch from yeast to hyphae, establishing it as a primary defect. Five genes, VPS15, IME2, PKH3, PGA43 and CEX1, encode proteins not previously reported to influence hyphal development or biofilm formation. Network analysis established that individual components of some processes, most interestingly MAP kinase pathways, are not required for biofilm formation, most likely indicating functional redundancy. Mutants were also screened for their response to bacterial supernatants and it was found that Pseudomonas aeruginosa supernatants inhibited biofilm formation in all mutants, regardless of the presence of homoserine lactones (HSLs). In contrast, Candida morphology was only affected by supernatant containing HSLs. This confirms the distinct HSL-dependent inhibition of filamentation and the HSL-independent impairment of biofilm development by P. aeruginosa.

  2. Effects of Mentha suaveolens Essential Oil Alone or in Combination with Other Drugs in Candida albicans

    PubMed Central

    Stringaro, Annarita; Vavala, Elisabetta; Pepi, Federico; Mignogna, Giuseppina; Garzoli, Stefania; Angiolella, Letizia

    2014-01-01

    Candidosis is the most important cause of fungal infections in humans. The yeast Candida albicans can form biofilms, and it is known that microbial biofilms play an important role in human diseases and are very difficult to treat. The prolonged treatment with drugs has often resulted in failure and resistance. Due to the emergence of multidrug resistance, alternatives to conventional antimicrobial therapy are needed. This study aims to analyse the effects induced by essential oil of Mentha suaveolens Ehrh (EOMS) on Candida albicans and its potential synergism when used in combination with conventional drugs. Morphological differences between control and EOMS treated yeast cells or biofilms were observed by scanning electron microscopy and transmission electron microscopy (SEM and TEM resp.,). In order to reveal the presence of cell cycle alterations, flow cytometry analysis was carried out as well. The synergic action of EOMS was studied with the checkerboard method, and the cellular damage induced by different treatments was analysed by TEM. The results obtained have demonstrated both the effects of EOMS on C. albicans yeast cells and biofilms and the synergism of EOMS when used in combination with conventional antifungal drugs as fluconazole (FLC) and micafungin (MCFG), and therefore we can hypothesize on its potential use in therapy. Further studies are necessary to know its mechanism of action. PMID:24719638

  3. Genotypes of Candida albicans isolated from healthy individuals and their distribution in patients with oral candidiasis.

    PubMed

    Takagi, Yuki; Fukano, Hideo; Shimozato, Kazuo; Tanaka, Reiko; Horii, Toshinobu; Kawamoto, Fumihiko; Kanbe, Toshio

    2013-12-01

    For the study of Candida albicans genotypes involved in development of candidiasis, Candida albicans isolates were collected from healthy volunteers and patients with oral candidiasis and genotyped on the basis of 25S rDNA and microsatellite polymorphisms. In the microsatellite analysis using two microsatellite markers (CDC3 and CAI), 63 healthy volunteer isolates were classified into 35 genotypes (allelic relations to CDC3 alleles 1:2/CAI alleles 1:2), among which genotypes II (115:119/23:23), III (115:123/18:27), and V (123:127/32:41) were found at frequencies of 12.7%, 7.9%, and 7.9%, respectively. In 68 oral candidiasis isolates classified into 39 genotypes, genotypes II and III were identified in 4.4% and 20.6% of the isolates, respectively. The frequency of genotype III was higher in the candidiasis isolates than in the healthy isolates (p < 0.05). These results suggest that genotype III C. albicans assigned by CDC3/CAI is related to the development of oral candidiasis.

  4. Effect of essential oils prepared from Thai culinary herbs on sessile Candida albicans cultures.

    PubMed

    Hovijitra, Ray S; Choonharuangdej, Suwan; Srithavaj, Theerathavaj

    2016-01-01

    Although medicinal herbs with fungicidal effects have been ubiquitously employed in traditional medicine, such effects of culinary herbs and spices still have to be elucidated. Therefore, it is noteworthy to determine the antifungal efficacy of some edible herbs used in Thai cuisine against sessile Candida albicans cultures, and to inquire if they can be further utilized as naturally-derived antifungals. Fourteen essential oils extracted from Thai culinary herbs and spices were tested for their antifungal activity against C. albicans using the agar disk diffusion method followed by broth micro-dilution method for the determination of minimum inhibitory concentration (MIC) and minimum fungicidal concentration. The oils with potent antifungal effects against planktonic fungi were then assessed for their effect against sessile fungus (adherent organisms and established biofilm culture). MIC of the oils against sessile C. albicans was evaluated by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide reduction assay. All selected culinary herbs and spices, except galangal, garlic, and turmeric, exhibited inhibitory effects on planktonic yeast cells. Cinnamon bark and sweet basil leaf essential oils exhibited potent fungicidal effect on planktonic and sessile fungus. Sessile MICs were 8-16 times higher than planktonic MICs. Consequently, both cinnamon bark and sweet basil leaf herbal oils seem to be highly effective anti-Candida choices. (J Oral Sci 58, 365-371, 2016). PMID:27665976

  5. Effects of Mentha suaveolens Essential Oil Alone or in Combination with Other Drugs in Candida albicans.

    PubMed

    Stringaro, Annarita; Vavala, Elisabetta; Colone, Marisa; Pepi, Federico; Mignogna, Giuseppina; Garzoli, Stefania; Cecchetti, Serena; Ragno, Rino; Angiolella, Letizia

    2014-01-01

    Candidosis is the most important cause of fungal infections in humans. The yeast Candida albicans can form biofilms, and it is known that microbial biofilms play an important role in human diseases and are very difficult to treat. The prolonged treatment with drugs has often resulted in failure and resistance. Due to the emergence of multidrug resistance, alternatives to conventional antimicrobial therapy are needed. This study aims to analyse the effects induced by essential oil of Mentha suaveolens Ehrh (EOMS) on Candida albicans and its potential synergism when used in combination with conventional drugs. Morphological differences between control and EOMS treated yeast cells or biofilms were observed by scanning electron microscopy and transmission electron microscopy (SEM and TEM resp.,). In order to reveal the presence of cell cycle alterations, flow cytometry analysis was carried out as well. The synergic action of EOMS was studied with the checkerboard method, and the cellular damage induced by different treatments was analysed by TEM. The results obtained have demonstrated both the effects of EOMS on C. albicans yeast cells and biofilms and the synergism of EOMS when used in combination with conventional antifungal drugs as fluconazole (FLC) and micafungin (MCFG), and therefore we can hypothesize on its potential use in therapy. Further studies are necessary to know its mechanism of action.

  6. Effect of essential oils prepared from Thai culinary herbs on sessile Candida albicans cultures.

    PubMed

    Hovijitra, Ray S; Choonharuangdej, Suwan; Srithavaj, Theerathavaj

    2016-01-01

    Although medicinal herbs with fungicidal effects have been ubiquitously employed in traditional medicine, such effects of culinary herbs and spices still have to be elucidated. Therefore, it is noteworthy to determine the antifungal efficacy of some edible herbs used in Thai cuisine against sessile Candida albicans cultures, and to inquire if they can be further utilized as naturally-derived antifungals. Fourteen essential oils extracted from Thai culinary herbs and spices were tested for their antifungal activity against C. albicans using the agar disk diffusion method followed by broth micro-dilution method for the determination of minimum inhibitory concentration (MIC) and minimum fungicidal concentration. The oils with potent antifungal effects against planktonic fungi were then assessed for their effect against sessile fungus (adherent organisms and established biofilm culture). MIC of the oils against sessile C. albicans was evaluated by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide reduction assay. All selected culinary herbs and spices, except galangal, garlic, and turmeric, exhibited inhibitory effects on planktonic yeast cells. Cinnamon bark and sweet basil leaf essential oils exhibited potent fungicidal effect on planktonic and sessile fungus. Sessile MICs were 8-16 times higher than planktonic MICs. Consequently, both cinnamon bark and sweet basil leaf herbal oils seem to be highly effective anti-Candida choices. (J Oral Sci 58, 365-371, 2016).

  7. Population Structure of Candida albicans from Three Teaching Hospitals in Ghana.

    PubMed

    Adjapong, Gloria; Hale, Marie; Garrill, Ashley

    2016-02-01

    Previous studies on Candida species in a clinical setting in Ghana have shown a prevalence of Candida albicans. Despite this, very little is known about the various strain types and their population genetic structure. In this study three microsatellite loci, CAI, CAIII and CAVI, were used to investigate the population genetic structure of C. albicans from clinical isolates in Ghana. In all, 240 clinically unrelated C. albicans isolates were recovered from patients reporting at three teaching hospitals. All the isolates were heterozygous for at least one of the three loci, except for one isolate, which was homozygous for all three loci. Sixty-seven unique alleles and 240 different genotypes were generated by the three polymorphic microsatellite loci, resulting in a very high discriminatory potential of approximately 0.98. There was no significant difference in allele frequencies from the small number of anatomical sites sampled, regardless of the host conditions although high genotypic diversities were observed among the isolates. There was evidence for clonal reproduction, including over-expression of observed heterozygotes across the populations. The populations deviated significantly from Hardy-Weinberg equilibrium and pair-wise genotypic linkage disequilibria comparisons across the three loci were significant, also suggesting a clonal population. The overall Wright FIS for the three loci was negative, and the overall FST value was not significantly different from zero for the three loci analyzed, indicating a clonal and homogeneous population across the three sampling locations from Ghana.

  8. Tumor necrosis factor as an autocrine and paracrine signal controlling the macrophage secretory response to Candida albicans.

    PubMed Central

    Blasi, E; Pitzurra, L; Bartoli, A; Puliti, M; Bistoni, F

    1994-01-01

    We have previously demonstrated that the hyphal form of Candida albicans (H-Candida), but not the yeast form (Y-Candida), acts as a macrophage-stimulating agent. The early response (1 to 3 h) of the macrophage cell line ANA-1 to H-Candida results in enhanced tumor necrosis factor (TNF) transcription and production. Here we show that when coincubation times are prolonged (3 to 24 h), Y-Candida also exhibits stimulatory properties. This phenomenon has been ascribed to the occurrence of the dimorphic transition, as demonstrated by microscopic evaluation of the cultures and by experiments in which both killed Y-Candida and the agerminative strain C. albicans PCA-2 failed to induce cytokine production. TNF produced in response to H-Candida acts as an autocrine and paracrine signal controlling the macrophage secretory response to C. albicans. In fact, addition of anti-TNF polyclonal antibodies to the coculture of ANA-1 macrophages and H-Candida results in a marked and time-dependent decrease of TNF transcript levels. Moreover, pretreatment of macrophages with recombinant TNF for 3 h enhances TNF and induces interleukin-1 production in response to both forms of Candida, while pretreatment for 18 h renders macrophages refractory to any stimuli. Interestingly, the kinetics of interleukin-1 transcription and secretion in response to H-Candida are delayed with respect to those of TNF. Overall, these data indicate that TNF, produced by macrophages in response to H-Candida, regulates its own production as well as that of other soluble factors, thus suggesting that this cytokine plays multiple roles in the immune mechanisms involved in Candida infection. Images PMID:8132326

  9. Candida albicans Carriage in Children with Severe Early Childhood Caries (S-ECC) and Maternal Relatedness

    PubMed Central

    Xiao, Jin; Moon, Yonghwi; Li, Lihua; Rustchenko, Elena; Wakabayashi, Hironao; Zhao, Xiaoyi; Feng, Changyong; Gill, Steven R.; McLaren, Sean; Malmstrom, Hans; Ren, Yanfang; Quivey, Robert

    2016-01-01

    Introduction Candida albicans has been detected together with Streptococcus mutans in high numbers in plaque-biofilm from children with early childhood caries (ECC). The goal of this study was to examine the C. albicans carriage in children with severe early childhood caries (S-ECC) and the maternal relatedness. Methods Subjects in this pilot cross-sectional study were recruited based on a convenient sample. DMFT(S)/dmft(s) caries and plaque scores were assessed during a comprehensive oral exam. Social-demographic and related background information was collected through a questionnaire. Saliva and plaque sample from all children and mother subjects were collected. C. albicans were isolated by BBL™ CHROMagar™ and also identified using germ tube test. S. mutans was isolated using Mitis Salivarius with Bacitracin selective medium and identified by colony morphology. Genetic relatedness was examined using restriction endonuclease analysis of the C. albicans genome using BssHII (REAG-B). Multilocus sequence typing was used to examine the clustering information of isolated C. albicans. Spot assay was performed to examine the C. albicans Caspofungin susceptibility between S-ECC children and their mothers. All statistical analyses (power analysis for sample size, Spearman’s correlation coefficient and multiple regression analyses) were implemented with SAS 9.4 Results A total of 18 S-ECC child-mother pairs and 17 caries free child-mother pairs were enrolled in the study. Results indicated high C. albicans carriage rate in the oral cavity (saliva and plaque) of both S-ECC children and their mothers (>80%). Spearman’s correlation coefficient also indicated a significant correlation between salivary and plaque C. albicans and S. mutans carriage (p<0.01) and caries severity (p<0.05). The levels of C. albicans in the prepared saliva and plaque sample (1ml resuspension) of S-ECC children were 1.3 ± 4.5 x104 cfu/ml and 1.2 ± 3.5 x104 cfu/ml (~3-log higher vs. caries

  10. Early differential molecular response of a macrophage cell line to yeast and hyphal forms of Candida albicans.

    PubMed Central

    Blasi, E; Pitzurra, L; Puliti, M; Lanfrancone, L; Bistoni, F

    1992-01-01

    The dimorphic transition of Candida albicans from the yeast (Y-Candida) to the hyphal (H-Candida) form is a complex event; the relevance of this transition in fungal pathogenicity is still poorly understood. By using a cloned macrophage cell line (ANA-1), we questioned whether the interaction between macrophages and Y-Candida or H-Candida could affect specific cell functions, i.e., tumor necrosis factor and lysozyme production. We found that ANA-1 macrophages selectively responded to H-Candida with increased tumor necrosis factor and downregulated lysozyme, as assessed by measurement of relative mRNA levels and secreted biological activities. The H-Candida-mediated effects were (i) dependent upon the ratio between ANA-1 macrophages and H-Candida, (ii) detectable after 1 h of coincubation, and (iii) accomplished without fungal ingestion. Conversely, Y-Candida, which was found inside the ANA-1 macrophages, did not affect tumor necrosis factor and lysozyme production, nor did it prevent the macrophage response to other stimuli. Overall, these results indicate that a macrophage can distinguish between Y-Candida and H-Candida and that only the latter is able to modulate specific functions. H-Candida is recognized and probably processed as an extracellular target. The possible implication of macrophages as autocrine and paracrine regulatory cells during Candida infections is discussed. Images PMID:1541557

  11. Diorcinol D Exerts Fungicidal Action against Candida albicans through Cytoplasm Membrane Destruction and ROS Accumulation.

    PubMed

    Li, Ying; Chang, Wenqiang; Zhang, Ming; Li, Xiaobin; Jiao, Yang; Lou, Hongxiang

    2015-01-01

    Candida albicans, which is the most common human fungal pathogen, causes high mortality among immunocompromised patients. Antifungal drug resistance becomes a major challenge for the management of Candida infection. Diorcinol D (DD), a diphenyl ether derivative isolated from an endolichenic fungus, exerted fungicidal action against Candida species. In this study, we investigated the possible mechanism of its antifungal activity. The change of membrane dynamics and permeability suggested that the cell membrane was disrupted by the treatment of DD. This was further supported by the evidences of intracellular glycerol accumulation, alteration of cell ultrastructure, and down-regulation of genes involved in cell membrane synthesis. In addition, the treatment of C. albicans with DD resulted in the elevation of reactive oxygen species (ROS), which caused the dysfunction of mitochondria. These altogether suggested that DD exerted its antifungal activity through cytoplasmic membrane destruction and ROS accumulation. This finding is helpful to uncover the underlying mechanisms for the diphenyl ether derivatives and provides a potential application in fighting clinical fungal infections. PMID:26047493

  12. Fluorometric determination of acid proteinase activity in Candida albicans strains from diabetic patients with vulvovaginal candidiasis.

    PubMed

    Yildirim, Zuhal; Kilic, Nedret; Kalkanci, Ayse

    2011-09-01

    Vulvovaginal candidiasis is one of the most frequent disorders in obstetrics and gynaecology. Approximately three-quarters of all adult women experience at least one episode of vulvovaginal candidiasis during their life span. Diabetes mellitus (DM) increases the rate of vaginal colonisation and infection with Candida species. The secreted acid proteinase might be especially relevant in the pathogenesis of vulvovaginal candidiasis. The aim of this study was to determine the acid proteinase activity in the samples of Candida albicans from diabetic patients with vulvovaginal candidiasis by a fluorometric method. Vaginal swabs were taken from 33 women (aged between 22 and 57 years) having symptoms of vaginitis. Patients were divided into three groups: control group, controlled diabetic group and uncontrolled diabetic group. The proteinase activity in the culture supernatants was determined by a modified fluorometric method. Acid proteinase activities were significantly increased in the uncontrolled diabetic group in comparison with both the control group and the controlled diabetic group (P < 0.05). Acid proteinase may play an important role in C. albicans pathogenesis in diabetic patients. Improving glucose control may reduce the risk of Candida colonisation and potentially symptomatic infection, among women with diabetes and hence may be useful even for weaker enzyme activity measurements.

  13. Production and function of cytokines in natural and acquired immunity to Candida albicans infection.

    PubMed Central

    Ashman, R B; Papadimitriou, J M

    1995-01-01

    Host resistance against infections caused by the yeast Candida albicans is mediated predominantly by polymorphonuclear leukocytes and macrophages. Antigens of Candida stimulate lymphocyte proliferation and cytokine synthesis, and in both humans and mice, these cytokines enhance the candidacidal functions of the phagocytic cells. In systemic candidiasis in mice, cytokine production has been found to be a function of the CD4+ T helper (Th) cells. The Th1 subset of these cells, characterized by the production of gamma interferon and interleukin-2, is associated with macrophage activation and enhanced resistance against reinfection, whereas the Th2 subset, which produces interleukins-4, -6, and -10, is linked to the development of chronic disease. However, other models have generated divergent data. Mucosal infection generally elicits Th1-type cytokine responses and protection from systemic challenge, and identification of cytokine mRNA present in infected tissues of mice that develop mild or severe lesions does not show pure Th1- or Th2-type responses. Furthermore, antigens of C. albicans, mannan in particular, can induce suppressor cells that modulate both specific and nonspecific cellular and humoral immune responses, and there is an emerging body of evidence that molecular mimicry may affect the efficiency of anti-Candida responses within defined genetic contexts. PMID:8531890

  14. Inhibitors of the Glyoxylate Cycle Enzyme ICL1 in Candida albicans for Potential Use as Antifungal Agents

    PubMed Central

    Cheah, Hong-Leong; Lim, Vuanghao; Sandai, Doblin

    2014-01-01

    Candida albicans is an opportunistic pathogen that causes candidiasis in humans. In recent years, metabolic pathways in C. albicans have been explored as potential antifungal targets to treat candidiasis. The glyoxylate cycle, which enables C. albicans to survive in nutrient-limited host niches and its. Key enzymes (e.g., isocitrate lyase (ICL1), are particularly attractive antifungal targets for C. albicans. In this study, we used a new screening approach that better reflects the physiological environment that C. albicans cells experience during infection to identify potential inhibitors of ICL. Three compounds (caffeic acid (CAFF), rosmarinic acid (ROS), and apigenin (API)) were found to have antifungal activity against C. albicans when tested under glucose-depleted conditions. We further confirmed the inhibitory potential of these compounds against ICL using the ICL enzyme assay. Lastly, we assessed the bioavailability and toxicity of these compounds using Lipinski's rule-of-five and ADMET analysis. PMID:24781056

  15. In Vitro and In Vivo Antifungal Activity of Lichochalcone-A against Candida albicans Biofilms

    PubMed Central

    Seleem, Dalia; Benso, Bruna; Noguti, Juliana; Pardi, Vanessa; Murata, Ramiro Mendonça

    2016-01-01

    Oral candidiasis (OC) is an opportunistic fungal infection with high prevalence among immunocompromised patients. Candida albicans is the most common fungal pathogen responsible for OC, often manifested in denture stomatitis and oral thrush. Virulence factors, such as biofilms formation and secretion of proteolytic enzymes, are key components in the pathogenicity of C. albicans. Given the limited number of available antifungal therapies and the increase in antifungal resistance, demand the search for new safe and effective antifungal treatments. Lichochalcone-A is a polyphenol natural compound, known for its broad protective activities, as an antimicrobial agent. In this study, we investigated the antifungal activity of lichochalcone-A against C. albicans biofilms both in vitro and in vivo. Lichochalcone-A (625 μM; equivalent to 10x MIC) significantly reduced C. albicans (MYA 2876) biofilm growth compared to the vehicle control group (1% ethanol), as indicated by the reduction in the colony formation unit (CFU)/ml/g of biofilm dry weight. Furthermore, proteolytic enzymatic activities of proteinases and phospholipases, secreted by C. albicans were significantly decreased in the lichochalcone-A treated biofilms. In vivo model utilized longitudinal imaging of OC fungal load using a bioluminescent-engineered C. albicans (SKCa23-ActgLUC) and coelenterazine substrate. Mice treated with lichochalcone-A topical treatments exhibited a significant reduction in total photon flux over 4 and 5 days post-infection. Similarly, ex vivo analysis of tongue samples, showed a significant decrease in CFU/ml/mg in tongue tissue sample of lichochalcone-A treated group, which suggest the potential of lichochalcone-A as a novel antifungal agent for future clinical use. PMID:27284694

  16. Melanocytes and melanin represent a first line of innate immunity against Candida albicans.

    PubMed

    Tapia, Cecilia V; Falconer, Maryanne; Tempio, Fabián; Falcón, Felipe; López, Mercedes; Fuentes, Marisol; Alburquenque, Claudio; Amaro, José; Bucarey, Sergio A; Di Nardo, Anna

    2014-07-01

    Melanocytes are dendritic cells located in the skin and mucosae that synthesize melanin. Some infections induce hypo- or hyperpigmentation, which is associated with the activation of Toll-like receptors (TLRs), especially TLR4. Candida albicans is an opportunist pathogen that can switch between blastoconidia and hyphae forms; the latter is associated with invasion. Our objectives in this study were to ascertain whether C. albicans induces pigmentation in melanocytes and whether this process is dependent on TLR activation, as well as relating this with the antifungal activity of melanin as a first line of innate immunity against fungal infections. Normal human melanocytes were stimulated with C. albicans supernatants or with crude extracts of the blastoconidia or hyphae forms, and pigmentation and TLR2/TLR4 expression were measured. Expression of the melanosomal antigens Melan-A and gp100 was examined for any correlation with increased melanin levels or antifungal activity in melanocyte lysates. Melanosomal antigens were induced earlier than cell pigmentation, and hyphae induced stronger melanization than blastoconidia. Notably, when melanocytes were stimulated with crude extracts of C. albicans, the cell surface expression of TLR2/TLR4 began at 48 h post-stimulation and peaked at 72 h. At this time, blastoconidia induced both TLR2 and TLR4 expression, whereas hyphae only induced TLR4 expression. Taken together, these results suggest that melanocytes play a key role in innate immune responses against C. albicans infections by recognizing pathogenic forms of C. albicans via TLR4, resulting in increased melanin content and inhibition of infection.

  17. Identification of sialic acids on the cell surface of Candida albicans.

    PubMed

    Soares, R M; de A Soares, R M; Alviano, D S; Angluster, J; Alviano, C S; Travassos, L R

    2000-04-01

    The cell-surface expression of sialic acids in two isolates of Candida albicans was analyzed by thin-layer and gas chromatography, binding of lectins, colorimetry, sialidase treatment and flow cytofluorimetry with fluorescein-labeled lectins. N-acetylneuraminic acid (NANA) was the only derivative found in both strains of C. albicans grown in a chemically defined medium. Its identification was confirmed by mass spectrometry in comparison with an authentic standard. The density of sialic acid residues per cell ranged from 1. 6x10(6) to 2.8x10(6). The surface distribution of sialic acids over the entire C. albicans was inferred from labeling with fluorescein-Limulus polyphemus and Limax flavus agglutinins and directly observed by optical microscopy with (FITC)-Sambucus nigra agglutinin (SNA), abrogated by previous treatment of yeasts with bacterial sialidase. Sialidase-treated yeasts generated beta-galactopyranosyl terminal residues that reacted with peanut agglutinin. In C. albicans N-acetyl-neuraminic acids are alpha2,6- and alpha2,3-linked as indicated by yeast binding to SNA and Maackia amurensis agglutinin. The alpha2,6-linkage clearly predominated in both strains. We also investigated the contribution of sialic acids to the electronegativity of C. albicans, an important factor determining fungal interactions in vivo. Adhesion of yeast cells to a cationic solid phase substrate (poly-L-lysine) was mediated in part by sialic acids, since the number of adherent cells was significantly reduced after treatment with bacterial sialidase. The present evidence adds C. albicans to the list of pathogenic fungi that synthesize sialic acids, which contribute to the negative charge of fungal cells and have a role in their specific interaction with the host tissue.

  18. In Vitro and In Vivo Activities of Pterostilbene against Candida albicans Biofilms

    PubMed Central

    Li, De-Dong; Zhao, Lan-Xue; Mylonakis, Eleftherios; Hu, Gan-Hai; Zou, Yong; Huang, Tong-Kun; Yan, Lan

    2014-01-01

    Pterostilbene (PTE) is a stilbene-derived phytoalexin that originates from several natural plant sources. In this study, we evaluated the activity of PTE against Candida albicans biofilms and explored the underlying mechanisms. In 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assays, biofilm biomass measurement, confocal laser scanning microscopy, and scanning electron microscopy, we found that ≤16 μg/ml PTE had a significant effect against C. albicans biofilms in vitro, while it had no fungicidal effect on planktonic C. albicans cells, which suggested a unique antibiofilm effect of PTE. Then we found that PTE could inhibit biofilm formation and destroy the maintenance of mature biofilms. At 4 μg/ml, PTE decreased cellular surface hydrophobicity (CSH) and suppressed hyphal formation. Gene expression microarrays and real-time reverse transcription-PCR showed that exposure of C. albicans to 16 μg/ml PTE altered the expression of genes that function in morphological transition, ergosterol biosynthesis, oxidoreductase activity, and cell surface and protein unfolding processes (heat shock proteins). Filamentation-related genes, especially those regulated by the Ras/cyclic AMP (cAMP) pathway, including ECE1, ALS3, HWP1, HGC1, and RAS1 itself, were downregulated upon PTE treatment, indicating that the antibiofilm effect of PTE was related to the Ras/cAMP pathway. Then, we found that the addition of exogenous cAMP reverted the PTE-induced filamentous growth defect. Finally, with a rat central venous catheter infection model, we confirmed the in vivo activity of PTE against C. albicans biofilms. Collectively, PTE had strong activities against C. albicans biofilms both in vitro and in vivo, and these activities were associated with the Ras/cAMP pathway. PMID:24514088

  19. Rapid Detection of Candida albicans by Polymerase Spiral Reaction Assay in Clinical Blood Samples.

    PubMed

    Jiang, Xiaoqun; Dong, Derong; Bian, Lihong; Zou, Dayang; He, Xiaoming; Ao, Da; Yang, Zhan; Huang, Simo; Liu, Ningwei; Liu, Wei; Huang, Liuyu

    2016-01-01

    Candida albicans is the most common human yeast pathogen which causes mucosal infections and invasive fungal diseases. Early detection of this pathogen is needed to guide preventative and therapeutic treatment. The aim of this study was to establish a polymerase spiral reaction (PSR) assay that rapidly and accurately detects C. albicans and to assess the clinical applicability of PSR-based diagnostic testing. Internal transcribed spacer 2 (ITS2), a region between 5.8S and 28S fungal ribosomal DNA, was used as the target sequence. Four primers were designed for amplification of ITS2 with the PSR method, which was evaluated using real time turbidity monitoring and visual detection using a pH indicator. Fourteen non-C. albicans yeast strains were negative for detection, which indicated the specificity of PSR assay was 100%. A 10-fold serial dilution of C. albicans genomic DNA was subjected to PSR and conventional polimerase chain reaction (PCR) to compare their sensitivities. The detection limit of PSR was 6.9 pg/μl within 1 h, 10-fold higher than that of PCR (69.0 pg/μl). Blood samples (n = 122) were collected from intensive care unit and hematological patients with proven or suspected C. albicans infection at two hospitals in Beijing, China. Both PSR assay and the culture method were used to analyze the samples. Of the 122 clinical samples, 34 were identified as positive by PSR. The result was consistent with those obtained by the culture method. In conclusion, a novel and effective C. albicans detection assay was developed that has a great potential for clinical screening and point-of-care testing. PMID:27379048

  20. The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase of Candida albicans is a surface antigen.

    PubMed Central

    Gil-Navarro, I; Gil, M L; Casanova, M; O'Connor, J E; Martínez, J P; Gozalbo, D

    1997-01-01

    A lambda gt11 cDNA library from Candida albicans ATCC 26555 was screened by using pooled sera from two patients with systemic candidiasis and five neutropenic patients with high levels of anti-C. albicans immunoglobulin M antibodies. Seven clones were isolated from 60,000 recombinant phages. The most reactive one contained a 0.9-kb cDNA encoding a polypeptide immunoreactive only with sera from patients with systemic candidiasis. The whole gene was isolated from a genomic library by using the cDNA as a probe. The nucleotide sequence of the coding region showed homology (78 to 79%) to the Saccharomyces cerevisiae TDH1 to TDH3 genes coding for glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and their amino acid sequences showed 76% identity; thus, this gene has been named C. albicans TDH1. A rabbit polyclonal antiserum against the purified cytosolic C. albicans GAPDH (polyclonal antibody [PAb] anti-CA-GAPDH) was used to identify the GAPDH in the beta-mercaptoethanol extracts containing cell wall moieties. Indirect immunofluorescence demonstrated the presence of GAPDH at the C. albicans cell surface, particularly on the blastoconidia. Semiquantitative flow cytometry analysis showed the sensitivity of this GAPDH form to trypsin and its resistance to be removed with 2 M NaCl or 2% sodium dodecyl sulfate. The decrease in fluorescence in the presence of soluble GAPDH indicates the specificity of the labelling. In addition, a dose-dependent GAPDH enzymatic activity was detected in intact blastoconidia and germ tube cells. This activity was reduced by pretreatment of the cells with trypsin, formaldehyde, and PAb anti-CA-GAPDH. These observations indicate that an immunogenic, enzymatically active cell wall-associated form of the glycolytic enzyme GAPDH is found at the cell surface of C. albicans cells. PMID:9260938

  1. In Vitro and In Vivo Antifungal Activity of Lichochalcone-A against Candida albicans Biofilms.

    PubMed

    Seleem, Dalia; Benso, Bruna; Noguti, Juliana; Pardi, Vanessa; Murata, Ramiro Mendonça

    2016-01-01

    Oral candidiasis (OC) is an opportunistic fungal infection with high prevalence among immunocompromised patients. Candida albicans is the most common fungal pathogen responsible for OC, often manifested in denture stomatitis and oral thrush. Virulence factors, such as biofilms formation and secretion of proteolytic enzymes, are key components in the pathogenicity of C. albicans. Given the limited number of available antifungal therapies and the increase in antifungal resistance, demand the search for new safe and effective antifungal treatments. Lichochalcone-A is a polyphenol natural compound, known for its broad protective activities, as an antimicrobial agent. In this study, we investigated the antifungal activity of lichochalcone-A against C. albicans biofilms both in vitro and in vivo. Lichochalcone-A (625 μM; equivalent to 10x MIC) significantly reduced C. albicans (MYA 2876) biofilm growth compared to the vehicle control group (1% ethanol), as indicated by the reduction in the colony formation unit (CFU)/ml/g of biofilm dry weight. Furthermore, proteolytic enzymatic activities of proteinases and phospholipases, secreted by C. albicans were significantly decreased in the lichochalcone-A treated biofilms. In vivo model utilized longitudinal imaging of OC fungal load using a bioluminescent-engineered C. albicans (SKCa23-ActgLUC) and coelenterazine substrate. Mice treated with lichochalcone-A topical treatments exhibited a significant reduction in total photon flux over 4 and 5 days post-infection. Similarly, ex vivo analysis of tongue samples, showed a significant decrease in CFU/ml/mg in tongue tissue sample of lichochalcone-A treated group, which suggest the potential of lichochalcone-A as a novel antifungal agent for future clinical use. PMID:27284694

  2. Rapid Detection of Candida albicans by Polymerase Spiral Reaction Assay in Clinical Blood Samples

    PubMed Central

    Jiang, Xiaoqun; Dong, Derong; Bian, Lihong; Zou, Dayang; He, Xiaoming; Ao, Da; Yang, Zhan; Huang, Simo; Liu, Ningwei; Liu, Wei; Huang, Liuyu

    2016-01-01

    Candida albicans is the most common human yeast pathogen which causes mucosal infections and invasive fungal diseases. Early detection of this pathogen is needed to guide preventative and therapeutic treatment. The aim of this study was to establish a polymerase spiral reaction (PSR) assay that rapidly and accurately detects C. albicans and to assess the clinical applicability of PSR-based diagnostic testing. Internal transcribed spacer 2 (ITS2), a region between 5.8S and 28S fungal ribosomal DNA, was used as the target sequence. Four primers were designed for amplification of ITS2 with the PSR method, which was evaluated using real time turbidity monitoring and visual detection using a pH indicator. Fourteen non-C. albicans yeast strains were negative for detection, which indicated the specificity of PSR assay was 100%. A 10-fold serial dilution of C. albicans genomic DNA was subjected to PSR and conventional polimerase chain reaction (PCR) to compare their sensitivities. The detection limit of PSR was 6.9 pg/μl within 1 h, 10-fold higher than that of PCR (69.0 pg/μl). Blood samples (n = 122) were collected from intensive care unit and hematological patients with proven or suspected C. albicans infection at two hospitals in Beijing, China. Both PSR assay and the culture method were used to analyze the samples. Of the 122 clinical samples, 34 were identified as positive by PSR. The result was consistent with those obtained by the culture method. In conclusion, a novel and effective C. albicans detection assay was developed that has a great potential for clinical screening and point-of-care testing. PMID:27379048

  3. In vitro expression of Candida albicans alcohol dehydrogenase genes involved in acetaldehyde metabolism.

    PubMed

    Bakri, M M; Rich, A M; Cannon, R D; Holmes, A R

    2015-02-01

    Alcohol consumption is a risk factor for oral cancer, possibly via its conversion to acetaldehyde, a known carcinogen. The oral commensal yeast Candida albicans may be one of the agents responsible for this conversion intra-orally. The alcohol dehydrogenase (Adh) family of enzymes are involved in acetaldehyde metabolism in yeast but, for C. albicans it is not known which family member is responsible for the conversion of ethanol to acetaldehyde. In this study we determined the expression of mRNAs from three C. albicans Adh genes (CaADH1, CaADH2 and CaCDH3) for cells grown in different culture media at different growth phases by Northern blot analysis and quantitative reverse transcription polymerase chain reaction. CaADH1 was constitutively expressed under all growth conditions but there was differential expression of CaADH2. CaADH3 expression was not detected. To investigate whether CaAdh1p or CaAdh2p can contribute to alcohol catabolism in C. albicans, each gene from the reference strain C. albicans SC5314 was expressed in Saccharomyces cerevisiae. Cell extracts from an CaAdh1p-expressing S. cerevisiae recombinant, but not an CaAdh2p-expressing recombinant, or an empty vector control strain, possessed ethanol-utilizing Adh activity above endogenous S. cerevisiae activity. Furthermore, expression of C. albicans Adh1p in a recombinant S. cerevisiae strain in which the endogenous ScADH2 gene (known to convert ethanol to acetaldehyde in this yeast) had been deleted, conferred an NAD-dependent ethanol-utilizing, and so acetaldehyde-producing, Adh activity. We conclude that CaAdh1p is the enzyme responsible for ethanol use under in vitro growth conditions, and may contribute to the intra-oral production of acetaldehyde.

  4. Assessment of antifungal activity of herbal and conventional toothpastes against clinical isolates of Candida albicans

    PubMed Central

    Adwan, Ghaleb; Salameh, Yousef; Adwan, Kamel; Barakat, Ali

    2012-01-01

    Objective To detect the anticandidal activity of nine toothpastes containing sodium fluoride, sodium monofluorophosphate and herbal extracts as an active ingredients against 45 oral and non oral Candida albicans (C. albicans) isolates. Methods The antifungal activity of these toothpaste formulations was determined using a standard agar well diffusion method. Statistical analysis was performed using a statistical package, SPSS windows version 15, by applying mean values using one-way ANOVA with post-hoc least square differences (LSD) method. A P value of less than 0.05 was considered significant. Results All toothpastes studied in our experiments were effective in inhibiting the growth of all C. albicans isolates. The highest anticandidal activity was obtained from toothpaste that containing both herbal extracts and sodium fluoride as active ingredients, while the lowest activity was obtained from toothpaste containing sodium monofluorophosphate as an active ingredient. Antifungal activity of Parodontax toothpaste showed a significant difference (P< 0.001) against C. albicans isolates compared to toothpastes containing sodium fluoride or herbal products. Conclusions In the present study, it has been demonstrated that toothpaste containing both herbal extracts and sodium fluoride as active ingredients are more effective in control of C. albicans, while toothpaste that containing monofluorophosphate as an active ingredient is less effective against C. albicans. Some herbal toothpaste formulations studied in our experiments, appear to be equally effective as the fluoride dental formulations and it can be used as an alternative to conventional formulations for individuals who have an interest in naturally-based products. Our results may provide invaluable information for dental professionals. PMID:23569933

  5. Staphylococcus aureus adherence to Candida albicans hyphae is mediated by the hyphal adhesin Als3p

    PubMed Central

    Peters, Brian M.; Ovchinnikova, Ekaterina S.; Krom, Bastiaan P.; Schlecht, Lisa Marie; Zhou, Han; Hoyer, Lois L.; Busscher, Henk J.; van der Mei, Henny C.; Jabra-Rizk, Mary Ann

    2012-01-01

    The bacterium Staphylococcus (St.) aureus and the opportunistic fungus Candida albicans are currently among the leading nosocomial pathogens, often co-infecting critically ill patients, with high morbidity and mortality. Previous investigations have demonstrated preferential adherence of St. aureus to C. albicans hyphae during mixed biofilm growth. In this study, we aimed to characterize the mechanism behind this observed interaction. C. albicans adhesin-deficient mutant strains were screened by microscopy to identify the specific receptor on C. albicans hyphae recognized by St. aureus. Furthermore, an immunoassay was developed to validate and quantify staphylococcal binding to fungal biofilms. The findings from these experiments implicated the C. albicans adhesin agglutinin-like sequence 3 (Als3p) in playing a major role in the adherence process. This association was quantitatively established using atomic force microscopy, in which the adhesion force between single cells of the two species was significantly reduced for a C. albicans mutant strain lacking als3. Confocal microscopy further confirmed these observations, as St. aureus overlaid with a purified recombinant Als3 N-terminal domain fragment (rAls3p) exhibited robust binding. Importantly, a strain of Saccharomyces cerevisiae heterologously expressing Als3p was utilized to further confirm this adhesin as a receptor for St. aureus. Although the parental strain does not bind bacteria, expression of Als3p on the cell surface conferred upon the yeast the ability to strongly bind St. aureus. To elucidate the implications of these in vitro findings in a clinically relevant setting, an ex vivo murine model of co-infection was designed using murine tongue explants. Fluorescent microscopic images revealed extensive hyphal penetration of the epithelium typical of C. albicans mucosal infection. Interestingly, St. aureus bacterial cells were only seen within the epithelial tissue when associated with the invasive

  6. Antimicrobial effects of Piper hispidum extract, fractions and chalcones against Candida albicans and Staphylococcus aureus.

    PubMed

    Costa, G M; Endo, E H; Cortez, D A G; Nakamura, T U; Nakamura, C V; Dias Filho, B P

    2016-09-01

    Three chalcones, 2'-hydroxy-4,4',6'-trimethoxychalcone, 2'-hydroxy-4,4',6'-tetramethoxychalcone, and 3,2'-dihydroxy-4,4',6'-trimethoxychalcone, were isolated from the leaves of Piper hispidum in a bioguided fractionation of crude extract. The antimicrobial activity of crude extract of P. hispidum leaves was determined against bacteria Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus and yeasts Candida albicans, C. parapsilosis and C. tropicalis. Fractions and chalcones were tested against C. albicans and S. aureus. The checkerboard assay was performed to assess synergic interactions between extract and antifungal drugs, and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction assay was used to evaluate anti-biofilm effects of extract. The extract was active against yeasts, S. aureus and B. subtilis with MIC values between 15.6 and 62.5μg/mL. Synergistic effects of extract associated with fluconazole and nystatin were observed against C. albicans, with fractional inhibitory concentration indices of 0.37 and 0.24, respectively. The extract was also effective against C. albicans and S. aureus biofilm cells at concentrations of 62.5 and 200μg/mL, respectively. Thus, P. hispidum may be a possible source of bioactive substances with antimicrobial properties. PMID:27499460

  7. Antifungal activity, kinetics and molecular mechanism of action of garlic oil against Candida albicans

    PubMed Central

    Li, Wen-Ru; Shi, Qing-Shan; Dai, Huan-Qin; Liang, Qing; Xie, Xiao-Bao; Huang, Xiao-Mo; Zhao, Guang-Ze; Zhang, Li-Xin

    2016-01-01

    The antifungal activity, kinetics, and molecular mechanism of action of garlic oil against Candida albicans were investigated in this study using multiple methods. Using the poisoned food technique, we determined that the minimum inhibitory concentration of garlic oil was 0.35 μg/mL. Observation by transmission electron microscopy indicated that garlic oil could penetrate the cellular membrane of C. albicans as well as the membranes of organelles such as the mitochondria, resulting in organelle destruction and ultimately cell death. RNA sequencing analysis showed that garlic oil induced differential expression of critical genes including those involved in oxidation-reduction processes, pathogenesis, and cellular response to drugs and starvation. Moreover, the differentially expressed genes were mainly clustered in 19 KEGG pathways, representing vital cellular processes such as oxidative phosphorylation, the spliceosome, the cell cycle, and protein processing in the endoplasmic reticulum. In addition, four upregulated proteins selected after two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE) analysis were identified with high probability by mass spectrometry as putative cytoplasmic adenylate kinase, pyruvate decarboxylase, hexokinase, and heat shock proteins. This is suggestive of a C. albicans stress responses to garlic oil treatment. On the other hand, a large number of proteins were downregulated, leading to significant disruption of the normal metabolism and physical functions of C. albicans. PMID:26948845

  8. [Examination of the genetic variability among biofilm-forming Candida albicans clinical isolates].

    PubMed

    Durán, Estela Liliana; Mujica, Maria Teresa; Jewtuchowicz, Virginia Marta; Finquelievich, Jorge Luis; Pinoni, Maria Victoria; Iovannitti, Cristina Adela

    2007-12-31

    Biofilms are microbial communities encased in a self-produced polymeric matrix and represent a common mode of microbial growth. Candida albicans is able to colonize the surface of catheters, prostheses, and epithelia, forming biofilms that are highly resistant to antimicrobial drugs. The objective of this study was the genotypic characterization of biofilm-forming C. albicans clinical isolates using RAPD (Random Amplified Polymorphic DNA). We have studied 25 clinical isolates of C. albicans from oral cavities, blood, skin, nail, stool, oesophagus biopsy and vaginal fluids from patients suffering from candidiasis. For each strain biofilm formation was analysed by measuring the ability to adhere to and grow on polystyrene plastic surfaces using XTT [2,3-bis(2-methoxi-4nitro-5sulfophenil)-2H tetrazolium-5carboxanilide] reduction assay. The similarity coefficients generated by RAPD using four different primers varied from 49 to 91%, indicating a high degree of genetic variability between the clinical isolates. The dendrogram clustered the isolates in four related groups, all groups included strains with very different abilities to form biofilms. The isolates with similar genotypes often showed very different biofilm formation abilities. Strains were grouped into clusters independently of their clinical sources. Our results suggested that a direct correlation does not exist between the biofilm-forming ability of natural populations of C. albicans and the genotype as determined by RAPD.

  9. Induction of the immune response suppression in mice inoculated with Candida albicans.

    PubMed

    Valdez, J C; Mesón, D E; Sirena, A; de Petrino, S F; Eugenia, M; de Jorrat, B B; de Valdex, M G

    1986-03-01

    There is a controversy in respect to the immunological response (humoral or cellular) concerning the defense against Candida albicans. Candidosis would induce sub-populations of suppressor cells in the host cell-immune response. This report tries to show the effect of different doses of C. albicans (alive or heat-killed) on the expression of cell-mediated and humoral immunity. The effect upon cell immunity was determined by inoculating different lots of singeneic mice, doses of varied concentration of C. albicans and checking for delayed-type hipersensitivity (D.T.H.). D.T.H. was also controlled in syngeneic normal mice which had previously been injected with inoculated mice spleen cells. Humoral immunity was assayed by measuring the induced blastogenesis by Pokeweed Mitogen on spleen mononuclear cells with different doses of C. albicans. Results obtained show that the different doses gave origin to: Suppression of humoral and cell response (10(8) alive); Suppression of only humoral response (10(6) alive); Suppression of cell response and increase of humoral response (10(9) dead); Increase of both responses (10(8) dead).

  10. MNL1 regulates weak acid-induced stress responses of the fungal pathogen Candida albicans.

    PubMed

    Ramsdale, Mark; Selway, Laura; Stead, David; Walker, Jan; Yin, Zhikang; Nicholls, Susan M; Crowe, Jonathan; Sheils, Emma M; Brown, Alistair J P

    2008-10-01

    MNL1, the Candida albicans homologue of an orphan Msn2-like gene (YER130c in Saccharomyces cerevisiae) has no known function. Here we report that MNL1 regulates weak acid stress responses. Deletion of MNL1 prevents the long-term adaptation of C. albicans cells to weak acid stresses and compromises their global transcriptional response under these conditions. The promoters of Mnl1-dependent genes contain a novel STRE-like element (SLE) that imposes Mnl1-dependent, weak acid stress-induced transcription upon a lacZ reporter in C. albicans. The SLE (HHYYCCCCTTYTY) is related to the Nrg1 response element (NRE) element recognized by the transcriptional repressor Nrg1. Deletion of NRG1 partially restores the ability of C. albicans mnl1 cells to adapt to weak acid stress, indicating that Mnl1 and Nrg1 act antagonistically to regulate this response. Molecular, microarray, and proteomic analyses revealed that Mnl1-dependent adaptation does not occur in cells exposed to proapoptotic or pronecrotic doses of weak acid, suggesting that Ras-pathway activation might suppress the Mnl1-dependent weak acid response in dying cells. Our work defines a role for this YER130c orthologue in stress adaptation and cell death. PMID:18653474

  11. Role of Aif1 in regulation of cell death under environmental stress in Candida albicans.

    PubMed

    Ma, Feiyang; Zhang, Yueqi; Wang, Yuzhou; Wan, Yajuan; Miao, Yunheng; Ma, Tianyu; Yu, Qilin; Li, Mingchun

    2016-09-01

    Apoptosis-inducing factor (AIF) is a conserved flavoprotein localized in the mitochondria, inducing apoptosis after translocation into the nucleus. However, its role in the important fungal pathogen, Candida albicans, remains to be investigated. In this study, we find that the C. albicans AIF protein Aif1, similar to its homologues in other organisms, is localized at the mitochondria and translocated into the nucleus under apoptosis-inducing conditions. Moreover, deletion of AIF1 causes attenuated apoptosis in this pathogen under apoptosis-inducing conditions, such as the treatment of 2 mm H2 O2 , 10 mm acetic acid or 0.08 mg/l caspofungin, and its overexpression enhances this process. Interestingly, treatment with high levels of these agents leads to reversed sensitivity of aif1Δ/Δ and the overexpression strain AIF1ov. In addition, the virulence of C. albicans is not affected by deletion or overexpression of AIF1. Hence, C. albicans Aif1, as a mitochondria-localized protein, plays a dual role in the regulation of cell death under different concentrations of the stress-caused agents. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27121326

  12. Antifungal activity, kinetics and molecular mechanism of action of garlic oil against Candida albicans.

    PubMed

    Li, Wen-Ru; Shi, Qing-Shan; Dai, Huan-Qin; Liang, Qing; Xie, Xiao-Bao; Huang, Xiao-Mo; Zhao, Guang-Ze; Zhang, Li-Xin

    2016-01-01

    The antifungal activity, kinetics, and molecular mechanism of action of garlic oil against Candida albicans were investigated in this study using multiple methods. Using the poisoned food technique, we determined that the minimum inhibitory concentration of garlic oil was 0.35 μg/mL. Observation by transmission electron microscopy indicated that garlic oil could penetrate the cellular membrane of C. albicans as well as the membranes of organelles such as the mitochondria, resulting in organelle destruction and ultimately cell death. RNA sequencing analysis showed that garlic oil induced differential expression of critical genes including those involved in oxidation-reduction processes, pathogenesis, and cellular response to drugs and starvation. Moreover, the differentially expressed genes were mainly clustered in 19 KEGG pathways, representing vital cellular processes such as oxidative phosphorylation, the spliceosome, the cell cycle, and protein processing in the endoplasmic reticulum. In addition, four upregulated proteins selected after two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE) analysis were identified with high probability by mass spectrometry as putative cytoplasmic adenylate kinase, pyruvate decarboxylase, hexokinase, and heat shock proteins. This is suggestive of a C. albicans stress responses to garlic oil treatment. On the other hand, a large number of proteins were downregulated, leading to significant disruption of the normal metabolism and physical functions of C. albicans. PMID:26948845

  13. Candida albicans CUG Mistranslation Is a Mechanism To Create Cell Surface Variation

    PubMed Central

    Miranda, Isabel; Silva-Dias, Ana; Rocha, Rita; Teixeira-Santos, Rita; Coelho, Carolina; Gonçalves, Teresa; Santos, Manuel A. S.; Pina-Vaz, Cidália; Solis, Norma V.; Filler, Scott G.; Rodrigues, Acácio G.

    2013-01-01

    ABSTRACT In the human fungal pathogen Candida albicans, the CUG codon is translated 97% of the time as serine and 3% of the time as leucine, which potentially originates an array of proteins resulting from the translation of a single gene. Genes encoding cell surface proteins are enriched in CUG codons; thus, CUG mistranslation may influence the interactions of the organism with the host. To investigate this, we compared a C. albicans strain that misincorporates 28% of leucine at CUGs with a wild-type parental strain. The first strain displayed increased adherence to inert and host molecules. In addition, it was less susceptible to phagocytosis by murine macrophages, probably due to reduced exposure of cell surface β-glucans. To prove that these phenotypes occurred due to serine/leucine exchange, the C. albicans adhesin and invasin ALS3 was expressed in Saccharomyces cerevisiae in its two natural isoforms (Als3p-Leu and Als3p-Ser). The cells with heterologous expression of Als3p-Leu showed increased adherence to host substrates and flocculation. We propose that CUG mistranslation has been maintained during the evolution of C. albicans due to its potential to generate cell surface variability, which significantly alters fungus-host interactions. PMID:23800396

  14. Antifungal effects of undecylenic acid on the biofilm formation of Candida albicans.

    PubMed

    Shi, Dongmei; Zhao, Yaxin; Yan, Hongxia; Fu, Hongjun; Shen, Yongnian; Lu, Guixia; Mei, Huan; Qiu, Ying; Li, Dongmei; Liu, Weida

    2016-05-01

    Undecylenic acid can effectively control skin fungal infection, but the mechanism of its fungal inhibition is unclear. Hyphal growth of Candida albicans (C. albicans) and biofilm formation have been well recognized as important virulence factors for the initiation of skin infection and late development of disseminated infection. In this study, we seek to investigate antifungal mechanisms of undecylenic acid by evaluating the virulence factors of C. albicans during biofilm formation. We found that undecylenic acid inhibits biofilm formation of C. albicans effectively with optimal concentration above 3 mM. In the presence of this compound, the morphological transition from yeast to filamentous phase is abolished ultimately when the concentration of undecylenic acid is above 4 mM. Meanwhile, the cell surface is crumpled, and cells display an atrophic appearance under scanning electron microscopy even with low concentration of drug treatment. On the other hand, the drug treatment decreases the transcriptions of hydrolytic enzymes such as secreted aspartic protease, lipase, and phospholipase. Hyphal formation related genes, like HWP1, are significantly reduced in transcriptional level in drug-treated biofilm condition as well. The down-regulated profile of these genes leads to a poorly organized biofilm in undecylenic acid treated environment.

  15. Antifungal effects of undecylenic acid on the biofilm formation of Candida albicans.

    PubMed

    Shi, Dongmei; Zhao, Yaxin; Yan, Hongxia; Fu, Hongjun; Shen, Yongnian; Lu, Guixia; Mei, Huan; Qiu, Ying; Li, Dongmei; Liu, Weida

    2016-05-01

    Undecylenic acid can effectively control skin fungal infection, but the mechanism of its fungal inhibition is unclear. Hyphal growth of Candida albicans (C. albicans) and biofilm formation have been well recognized as important virulence factors for the initiation of skin infection and late development of disseminated infection. In this study, we seek to investigate antifungal mechanisms of undecylenic acid by evaluating the virulence factors of C. albicans during biofilm formation. We found that undecylenic acid inhibits biofilm formation of C. albicans effectively with optimal concentration above 3 mM. In the presence of this compound, the morphological transition from yeast to filamentous phase is abolished ultimately when the concentration of undecylenic acid is above 4 mM. Meanwhile, the cell surface is crumpled, and cells display an atrophic appearance under scanning electron microscopy even with low concentration of drug treatment. On the other hand, the drug treatment decreases the transcriptions of hydrolytic enzymes such as secreted aspartic protease, lipase, and phospholipase. Hyphal formation related genes, like HWP1, are significantly reduced in transcriptional level in drug-treated biofilm condition as well. The down-regulated profile of these genes leads to a poorly organized biofilm in undecylenic acid treated environment. PMID:26902505

  16. Cell viability of Candida albicans against the antifungal activity of thymol.

    PubMed

    de Vasconcelos, Laís César; Sampaio, Fabio Correia; Albuquerque, Allan de Jesus dos Reis; Vasconcelos, Laurylene César de Souza

    2014-01-01

    Candida albicans is a commensal fungus, but circumstantially it may cause superficial infections of the mucous membranes, such as denture stomatitis, when a biofilm is formed on the surface of dental prostheses. This study evaluated the cell viability of C. albicans biofilms against the antifungal activity of thymol when compared with miconazole, by the fluorescence imaging using SYTO 9 and propidium iodide dyes, and counting of colony forming units. C. albicans standard strains (ATCC 11006) were used. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of drugs were determined by broth microdilution tests and the inoculum was standardized to match 0.5 on the McFarland scale (106 cfu/mL). Biofilms were grown on the surface of acrylic resin disks in parallel flow chambers from Sabouraud broth supplemented with 10% dextrose. For counting of colony forming units, the fungal solution was sequentially diluted and plated in Sabouraud dextrose agar. Data were analyzed using two-way ANOVA and Tukey's test (a=5%). Biofilms treated with thymol and miconazole presented low numbers of viable cells at the evaluated exposure times. There was statistically significant difference (p<0.05) when compared with control, and the mean value of the exposure times between miconazole and thymol did not differ significantly (p>0.05). In conclusion, both drugs have similar efficiency as antifungal agents against biofilms of C. albicans formed on acrylic surfaces. PMID:25250489

  17. A conserved mitogen-activated protein kinase pathway is required for mating in Candida albicans.

    PubMed

    Chen, Jiangye; Chen, Jing; Lane, Shelley; Liu, Haoping

    2002-12-01

    Candida albicans had been thought to lack a mating process until the recent discovery of a mating type-like locus and mating between MTLa and MTL(alpha) strains. To elucidate the molecular mechanisms that regulate mating in C. albicans, we examined the function of Cph1 and its upstream mitogen-activated protein (MAP) kinase pathway in mating, as they are homologues of the pheromone-responsive MAP kinase pathway in Saccharomyces cerevisiae. We found that overexpressing CPH1 in MTLa, but not in MTLa/alpha strains, induced the transcription of orthologues of S. cerevisiae pheromone-induced genes and also increased mating efficiency. Furthermore, cph1 and hst7 mutants were completely defective in mating, and cst20 and cek1 mutants showed reduced mating efficiency, as in S. cerevisiae. The partial mating defect in cek1 results from the presence of a functionally redundant MAP kinase, Cek2. CEK2 complemented the mating defect of a fus3 kss1 mutant of S. cerevisiae and was expressed only in MTLa or MTL(alpha), but not in MTLa/alpha cell types. Moreover, a cek1 cek2 double mutant was completely defective in mating. Our data suggest that the conserved MAP kinase pathway regulates mating in C. albicans. We also observed that C. albicans mating efficiency was greatly affected by medium composition, indicating the potential involvement of nutrient-sensing pathways in mating in addition to the MAP kinase pathway. PMID:12453219

  18. Efficacy of ferulic acid encapsulated chitosan nanoparticles against Candida albicans biofilm.

    PubMed

    Panwar, Richa; Pemmaraju, Suma C; Sharma, Asvene K; Pruthi, Vikas

    2016-06-01

    Candida albicans, an opportunistic fungal pathogen is a major causative agent of superficial to systemic life-threating biofilm infections on indwelling medical devices. These biofilms acts as double edge swords owing to their resistance towards antibiotics and immunological barriers. To overcome this threat ferulic acid encapsulated chitosan nanoparticles (FA-CSNPs) were formulated to assess its efficacy as an antibiofilm agent against C. albicans. These FA-CSNPs were synthesized using ionotropic gelation method and observed through field emission scanning electron microscopy (FESEM) and fluorescent microscopy. Assessment of successful encapsulation and stability of ferulic acid into chitosan nanoparticles was made using Fourier transform infrared spectrum (FTIR), (1)H NMR and thermal analyses. Synthesized FA-CSNPs, were found to be cytocompatible, when tested using Human Embryonic Kidney (HEK-293) cell lines. XTT assay revealed that FA-CSNPs reduced the cell metabolic activity of C. albicans upto 22.5% as compared to native ferulic acid (63%) and unloaded CSNPs (88%) after 24 h incubation. Disruption of C. albicans biofilm architecture was visualized by FESEM. Results highlighted the potential of FA-CSNPs to be used as an effective alternative to the conventional antifungal therapeutics. PMID:26930164

  19. Effect of nonylphenol on growth of Neurospora crassa and Candida albicans.

    PubMed

    Karley, A J; Powell, S I; Davies, J M

    1997-04-01

    The effects of the nonionic surfactant nonylphenol on the growth and morphologies of the filamentous fungus Neurospora crassa and the diploid yeast Candida albicans have been examined. Nonylphenol inhibited respiration and growth of N. crassa, effecting a 10-fold decrease in organism yield at 25 microM. Severe morphological defects were also induced: cell shape was abnormal and apical dominance was lost. Nonylphenol monoethoxylate (the parent compound of nonylphenol) was a less potent growth inhibitor and morphogen. The growth of the yeast form of C. albicans was sensitive to nonylphenol (inducing an order of magnitude decrease in specific growth rate with a 10-fold increase in dose concentration) but not nonylphenol monoethoxylate. Similarly, C. albicans ATP content was reduced and glucose-induced extracellular acidification was inhibited only by nonylphenol. Although estrogens may induce the dimorphic transition of C. albicans, nonylphenol (as an environmental estrogen mimic) failed to trigger germ tube formation under nonpermissive conditions and inhibited it under permissive conditions. The effects of nonylphenol are most readily explained as the result of uncoupling of respiration, which produces multiple physiological effects.

  20. Comparison of the in vitro Effect of Chemical and Herbal Mouthwashes on Candida albicans

    PubMed Central

    Talebi, Somayeh; Sabokbar, Azar; Riazipour, Majid; Saffari, Mohsen

    2014-01-01

    Background: During the recent decades research has focused to find scientific evidence for the effects of herbal medicines. Researchers are interested in herbal remedies for medication and aim to substitute herbal material instead of chemical formula with limited side effects for human being. Objectives: The aim of the current study was to compare the in vitro effect of herbal and chemical mouthwashes against Candida albicans. Materials and Methods: In this research, we used a standard strain of C. albicans, PTCC 5027. The suspension was made by a fresh culture of C. albicans (24 hours) and the optical density (turbidity equating to a McFarland standard of 0.5) was read at 530 nm. The C. albicans suspension was cultured on Sabouraud dextrose agar plate. Next, two wells were filled with mouthwashes and after incubation at 30ºC for 24 hours, the inhibition zone was measured. Minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of mouthwashes were determined. Data were analyzed using the SPSS software, independent T-tests and one-sided variance analysis (ANOVA-one way). Results: Based on these findings on agar diffusion with (P = 0.764), MIC and MFC tests (P = 0.879), there were no significant differences between the antifungal effect of herbal and chemical mouthwashes. Conclusions: This study showed that, chemical mouthwashes acted better than herbal mouthwashes and among different chemical mouthwashes, Oral B was most effective. PMID:25741429

  1. Induction of the immune response suppression in mice inoculated with Candida albicans.

    PubMed

    Valdez, J C; Mesón, D E; Sirena, A; de Petrino, S F; Eugenia, M; de Jorrat, B B; de Valdex, M G

    1986-03-01

    There is a controversy in respect to the immunological response (humoral or cellular) concerning the defense against Candida albicans. Candidosis would induce sub-populations of suppressor cells in the host cell-immune response. This report tries to show the effect of different doses of C. albicans (alive or heat-killed) on the expression of cell-mediated and humoral immunity. The effect upon cell immunity was determined by inoculating different lots of singeneic mice, doses of varied concentration of C. albicans and checking for delayed-type hipersensitivity (D.T.H.). D.T.H. was also controlled in syngeneic normal mice which had previously been injected with inoculated mice spleen cells. Humoral immunity was assayed by measuring the induced blastogenesis by Pokeweed Mitogen on spleen mononuclear cells with different doses of C. albicans. Results obtained show that the different doses gave origin to: Suppression of humoral and cell response (10(8) alive); Suppression of only humoral response (10(6) alive); Suppression of cell response and increase of humoral response (10(9) dead); Increase of both responses (10(8) dead). PMID:3520329

  2. The Ess1 prolyl isomerase is required for growth and morphogenetic switching in Candida albicans.

    PubMed Central

    Devasahayam, Gina; Chaturvedi, Vishnu; Hanes, Steven D

    2002-01-01

    Prolyl-isomerases (PPIases) are found in all organisms and are important for the folding and activity of many proteins. Of the 13 PPIases in Saccharomyces cerevisiae only Ess1, a parvulin-class PPIase, is essential for growth. Ess1 is required to complete mitosis, and Ess1 and its mammalian homolog, Pin1, interact directly with RNA polymerase II. Here, we isolate the ESS1 gene from the pathogenic fungus Candida albicans and show that it is functionally homologous to the S. cerevisiae ESS1. We generate conditional-lethal (ts) alleles of C. albicans ESS1 and use these mutations to demonstrate that ESS1 is essential for growth in C. albicans. We also show that reducing the dosage or activity of ESS1 blocks morphogenetic switching from the yeast to the hyphal and pseudohyphal forms under certain conditions. Analysis of double mutants of ESS1 and TUP1 or CPH1, two genes known to be involved in morphogenetic switching, suggests that ESS1 functions in the same pathway as CPH1 and upstream of or in parallel to TUP1. Given that switching is important for virulence of C. albicans, inhibitors of Ess1 might be useful as antifungal agents. PMID:11805043

  3. Synergy Between Polyvinylpyrrolidone-Coated Silver Nanoparticles and Azole Antifungal Against Drug-Resistant Candida albicans.

    PubMed

    Sun, Lingmei; Liao, Kai; Li, Yiping; Zhao, Lei; Liang, Sai; Guo, Dan; Hu, Jun; Wang, Dayong

    2016-03-01

    In the clinical practice, resistance of Candida albicans to antifungal agents has frequently emerged. Silver-nanoparticles (Ag-NPs) have been demonstrated to have the antifungal property. We investigated the potential for synergy between polyvinylpyrrolidone (PVP)-coated Ag-NPs and azole antifungal, such as fluconazole or voriconazole, against drug-resistant C. albicans strain CA10. When antifungal agent was examined alone, fluconazole and voriconazole did not kill drug-resistant C. albicans, and PVP-coated Ag-NPs had only the moderate killing ability. In contrast, the combinational treatment of PVP-coated Ag-NPs with fluconazole or voriconazole was effective in being against the drug-resistant C. albicans. After the combinational treatment, we detected the disruption of cell membrane integrity, the tendency of PVP-coated Ag-NPs to adhere to cell membrane, and the inhibition of budding process. Moreover, after the combinational treatment, the defects in ergosterol signaling and efflux pump functions were detected. Our results suggest that the combinational use of engineered nanomaterials (ENMs), such as PVP-coated Ag-NPs, with the conventional antifungal may be a viable strategy to combat drug-resistant fungal infection.

  4. Waikialoid A suppresses hyphal morphogenesis and inhibits biofilm development in pathogenic Candida albicans.

    PubMed

    Wang, Xiaoru; You, Jianlan; King, Jarrod B; Powell, Douglas R; Cichewicz, Robert H

    2012-04-27

    A chemically prolific strain of Aspergillus was isolated from a soil sample collected near Waikiki Beach, Honolulu, Hawaii. The fungus produced several secondary metabolites, which were purified and placed in our natural products library and were later screened for substances capable of inhibiting biofilm formation by Candida albicans. It was determined that one of the secondary metabolites from the Hawaiian fungal isolate, a new complex prenylated indole alkaloid named waikialoid A (1), inhibited biofilm formation with an IC(50) value of 1.4 μM. Another structurally unrelated, presumably polyketide metabolite, waikialide A (15), also inhibited C. albicans biofilm formation, but was much less potent (IC(50) value of 32.4 μM). Microscopy studies revealed that compound 1 also inhibited C. albicans hyphal morphogenesis. While metabolite 1 appears ineffective at disrupting preformed biofilms, the accumulated data indicate that the new compound may exert its activity against C. albicans during the early stages of surface colonization involving cell adherence, hyphal development, and/or biofilm assembly. Unlike some other stephacidin/notoamide compounds, metabolite 1 was not cytotoxic to fungi or human cells (up to 200 μM), which makes this an intriguing model compound for studying the adjunctive use of biofilm inhibitors in combination with standard antifungal antibiotics. PMID:22400916

  5. The Antifungal Plant Defensin HsAFP1 from Heuchera sanguinea Induces Apoptosis in Candida albicans

    PubMed Central

    Aerts, An M.; Bammens, Leen; Govaert, Gilmer; Carmona-Gutierrez, Didac; Madeo, Frank; Cammue, Bruno P. A.; Thevissen, Karin

    2011-01-01

    Plant defensins are active against plant and human pathogenic fungi (such as Candida albicans) and baker's yeast. However, they are non-toxic to human cells, providing a possible source for treatment of fungal infections. In this study, we characterized the mode of action of the antifungal plant defensin HsAFP1 from coral bells by screening the Saccharomyces cerevisiae deletion mutant library for mutants with altered HsAFP1 sensitivity and verified the obtained genetic data by biochemical assays in S. cerevisiae and C. albicans. We identified 84 genes, which when deleted conferred at least fourfold hypersensitivity or resistance to HsAFP1. A considerable part of these genes were found to be implicated in mitochondrial functionality. In line, sodium azide, which blocks the respiratory electron transport chain, antagonized HsAFP1 antifungal activity, suggesting that a functional respiratory chain is indispensable for HsAFP1 antifungal action. Since mitochondria are the main source of cellular reactive oxygen species (ROS), we investigated the ROS-inducing nature of HsAFP1. We showed that HsAFP1 treatment of C. albicans resulted in ROS accumulation. As ROS accumulation is one of the phenotypic markers of apoptosis in yeast, we could further demonstrate that HsAFP1 induced apoptosis in C. albicans. These data provide novel mechanistic insights in the mode of action of a plant defensin. PMID:21993350

  6. Synergy Between Polyvinylpyrrolidone-Coated Silver Nanoparticles and Azole Antifungal Against Drug-Resistant Candida albicans.

    PubMed

    Sun, Lingmei; Liao, Kai; Li, Yiping; Zhao, Lei; Liang, Sai; Guo, Dan; Hu, Jun; Wang, Dayong

    2016-03-01

    In the clinical practice, resistance of Candida albicans to antifungal agents has frequently emerged. Silver-nanoparticles (Ag-NPs) have been demonstrated to have the antifungal property. We investigated the potential for synergy between polyvinylpyrrolidone (PVP)-coated Ag-NPs and azole antifungal, such as fluconazole or voriconazole, against drug-resistant C. albicans strain CA10. When antifungal agent was examined alone, fluconazole and voriconazole did not kill drug-resistant C. albicans, and PVP-coated Ag-NPs had only the moderate killing ability. In contrast, the combinational treatment of PVP-coated Ag-NPs with fluconazole or voriconazole was effective in being against the drug-resistant C. albicans. After the combinational treatment, we detected the disruption of cell membrane integrity, the tendency of PVP-coated Ag-NPs to adhere to cell membrane, and the inhibition of budding process. Moreover, after the combinational treatment, the defects in ergosterol signaling and efflux pump functions were detected. Our results suggest that the combinational use of engineered nanomaterials (ENMs), such as PVP-coated Ag-NPs, with the conventional antifungal may be a viable strategy to combat drug-resistant fungal infection. PMID:27455637

  7. Characteristics of DTH suppressor cells in mice infected with Candida albicans.

    PubMed

    Valdez, J C; Mesón, O E; Sirena, A; de Alderete, N G

    1987-05-01

    Inoculation of 10(8) C. albicans intraperitoneally into Balb/c mice at given dosage was reported to induce suppression of antigen-specific delayed-type hypersensitivity. Adoptive transfer of spleen cells into normal syngeneic mice pre-treated with Cyclophosphamide confirmed the existence of suppressor cells in mice. Such cells were sensitive to treatment with anti-theta serum and complement, non-adherent to Sephadex G-10. A pretreatment of the mice with Cyclophosphamide eliminated DTH suppression. Treatment with antimacrophage agents via intraperitoneal abrogated suppression only if being effected before inoculation of alive 10(8) Candida albicans. It is concluded that the spleen suppressor cell is a T-lymphocyte whose precursor is Cyclophosphamide-sensitive, requiring the macrophage to be induced.

  8. Quick Detection of FKS1 Mutations Responsible for Clinical Echinocandin Resistance in Candida albicans

    PubMed Central

    Dudiuk, Catiana; Gamarra, Soledad; Jimenez-Ortigosa, Cristina; Leonardelli, Florencia; Macedo, Daiana; Perlin, David S.

    2015-01-01

    A rapid molecular-based assay for the detection of the Candida albicans FKS1 gene mutations responsible for resistance to echinocandin drugs was designed and evaluated. The assay consisted of a multiplexed PCR set of 5 tubes able to detect the most commonly described resistance mechanism, including FKS1 hot spot 1 and hot spot 2 mutations. The performance and specificity of the assay was evaluated using a double-blinded panel of 50 C. albicans strains. The assay showed a sensitivity of 96% and was able to detect all homozygous mutants included in the collection of strains, demonstrating that it is a robust, quick, and labor-saving method that is suitable for a routine clinical diagnostic laboratory. PMID:25878347

  9. 5-fluoro-orotic acid induces chromosome alterations in genetically manipulated strains of Candida albicans.

    PubMed

    Wellington, Melanie; Kabir, M Anaul; Rustchenko, Elena

    2006-01-01

    We previously reported the occurrence of chromosome alterations in a Candida albicans prototrophic strain 3153A treated with 5-fluoro-orotic acid (5-FOA). In this study we investigated the mutagenic properties of 5-FOA with two derivatives of C. albicans strain CAF4-2 (ura3/ura3), each containing an ectopic copy of URA3 gene (ura3/ ura3 URA3) on a different chromosome. As expected, after the ura3/ura3 URA3 constructs were applied to 5-FOA containing solid medium, the "pop-outs" that lost URA3 appeared. However most of the "pop-outs" acquired various chromosome alterations. Thus constructs exposed to 5-FOA should be examined for chromosome alterations or the use of 5-FOA should be avoided. PMID:17040068

  10. Candida albicans group A-specific soluble antigens demonstrated by quantitative immunoelectrophoresis.

    PubMed

    Guinet, R M; Gabriel, S M

    1980-09-01

    Soluble cytoplasmic extracts of Candida albicans groups A and B were prepared and compared by quantitative immunoelectrophoresis experiments performed with a commercial anti-C. albicans group A immune serum. Although crossed immunoelectrophoresis, tandem crossed immunoelectrophoresis, and line immunoelectrophoresis revealed many cross-reactions between the two groups, some components seemed to be specific to group A. However, the complexity of the extracts studied did not allow us to demonstrate specific constituents with these methods. Crossed-line immunoelectrophoresis with and without absorption of antibodies in situ was then used, and four specific antigens unique to group A cytoplasmic extract were demonstrated, one of which appeared to be quantitatively important. The value of various quantitative immunoelectrophoretic methods applied to complex antigenic preparations is discussed.

  11. Quick Detection of FKS1 Mutations Responsible for Clinical Echinocandin Resistance in Candida albicans.

    PubMed

    Dudiuk, Catiana; Gamarra, Soledad; Jimenez-Ortigosa, Cristina; Leonardelli, Florencia; Macedo, Daiana; Perlin, David S; Garcia-Effron, Guillermo

    2015-07-01

    A rapid molecular-based assay for the detection of the Candida albicans FKS1 gene mutations responsible for resistance to echinocandin drugs was designed and evaluated. The assay consisted of a multiplexed PCR set of 5 tubes able to detect the most commonly described resistance mechanism, including FKS1 hot spot 1 and hot spot 2 mutations. The performance and specificity of the assay was evaluated using a double-blinded panel of 50 C. albicans strains. The assay showed a sensitivity of 96% and was able to detect all homozygous mutants included in the collection of strains, demonstrating that it is a robust, quick, and labor-saving method that is suitable for a routine clinical diagnostic laboratory. PMID:25878347

  12. Candida albicans osteomyelitis as a cause of chest pain and visual loss.

    PubMed

    Magano, Rita; Cortez, Joana; Ramos, Evelise; Trindade, Luís

    2015-01-01

    Candida albicans osteomyelitis is a rare disease that occurs in immunocompromised individuals, sometimes with a late diagnosis related to the mismatch between symptoms and candidemia. This case refers to a 36-year-old male patient with a history of oesophageal surgery for achalasia with multiple subsequent surgeries and hospitalisation in the intensive care unit for oesophageal fistula complication. Four months after discharge, the patient was admitted to the infectious diseases department with pain in the 10th-12th left ribs, swelling of the 4th-6th costal cartilage and decreased visual acuity. An MRI study showed thickening and diffuse enhancement, with no defined borders in the cartilage and ribs, compatible with infection. After performing a CT-guided bone biopsy, isolated C. albicans sensitive to antifungal agents was detected. The patient started therapy with liposomal amphotericin B and maintenance fluconazole for 6 months and showed clinical and radiological improvement within this time. PMID:26475877

  13. Thiamin Pyrimidine Biosynthesis in Candida albicans: A Remarkable Reaction between Histidine and Pyridoxal Phosphate

    SciTech Connect

    Lai, Rung-Yi; Huang, Siyu; Fenwick, Michael K.; Hazra, Amrita; Zhang, Yang; Rajashankar, Kanagalaghatta; Philmus, Benjamin; Kinsland, Cynthia; Sanders, Jennie Mansell; Ealick, Steven E.; Begley, Tadhg P.

    2012-06-26

    In Saccharomyces cerevisiae, thiamin pyrimidine is formed from histidine and pyridoxal phosphate (PLP). The origin of all of the pyrimidine atoms has been previously determined using labeling studies and suggests that the pyrimidine is formed using remarkable chemistry that is without chemical or biochemical precedent. Here we report the overexpression of the closely related Candida albicans pyrimidine synthase (THI5p) and the reconstitution and preliminary characterization of the enzymatic activity. A structure of the C. albicans THI5p shows PLP bound at the active site via an imine with Lys62 and His66 in close proximity to the PLP. Our data suggest that His66 of the THI5 protein is the histidine source for pyrimidine formation and that the pyrimidine synthase is a single-turnover enzyme.

  14. Effect of alcohols on filamentation, growth, viability and biofilm development in Candida albicans.

    PubMed

    Chauhan, Nitin M; Shinde, Ravikumar B; Karuppayil, S Mohan

    2013-12-01

    In this study we report the potential of alcohols as morphogenetic regulators in Candida albicans. All the alcohols tested influenced various modes of growth like planktonic as well as biofilm forms. Viability was affected at high concentrations. Among the alcohols, the response of C. albicans to amyl alcohol (pentanol) was noteworthy. Amyl alcohol at a concentration 0.5% which was not inhibitory to growth and viability specifically inhibited morphogenetic switching from yeast to hyphal forms. It also inhibited normal biofilm development favoring yeast dominated biofilms. Based on this study we hypothesize that alcohols produced under anaerobic conditions may not favor biofilm development and support dissemination of yeast cells. Since anaerobic conditions are not found to favor production of quorum sensing molecules like farnesol, the alcohols may play a role in morphogenetic regulation. PMID:24688528

  15. Characteristics of DTH suppressor cells in mice infected with Candida albicans.

    PubMed

    Valdez, J C; Mesón, O E; Sirena, A; de Alderete, N G

    1987-05-01

    Inoculation of 10(8) C. albicans intraperitoneally into Balb/c mice at given dosage was reported to induce suppression of antigen-specific delayed-type hypersensitivity. Adoptive transfer of spleen cells into normal syngeneic mice pre-treated with Cyclophosphamide confirmed the existence of suppressor cells in mice. Such cells were sensitive to treatment with anti-theta serum and complement, non-adherent to Sephadex G-10. A pretreatment of the mice with Cyclophosphamide eliminated DTH suppression. Treatment with antimacrophage agents via intraperitoneal abrogated suppression only if being effected before inoculation of alive 10(8) Candida albicans. It is concluded that the spleen suppressor cell is a T-lymphocyte whose precursor is Cyclophosphamide-sensitive, requiring the macrophage to be induced. PMID:2439911

  16. Epidemiology of Candida infection. II. Application of biochemical methods for typing of Candida albicans strains.

    PubMed

    Budak, A

    1990-01-01

    Biochemical profiles of 350 C. albicans isolates from five towns in Poland and from Freiburg in Germany were determined on the basis of nine biochemical tests of Odds and Abbott method. API 20 C AUX system and additionally a resistogram. The analysis of the strains according to Odds' and Abbotts's system showed that investigated strains can be typed into 9 profile codes of common biochemical patterns. There were some differences among the profiles according to their geographical origin and anatomical sources of the isolation. On the basis of the ability C. albicans strains to assimilate of carbon sources, 350 isolates were categorised into 13 separate auxotrophic profiles with the major one: 2,576,174 accounting for 81% of the total. The majority of the investigated isolates were susceptible to antifungal agents (83%). A disproportionate distribution of auxotrophic profiles limited the use of resistogram method and API 20 C AUX as systems for typing C. albicans strains. On the other hand, the method of Odds and Abbott provides valuable criteria for typing of C. albicans. PMID:2130802

  17. Cold plasma-induced surface modification of heat-polymerized acrylic resin and prevention of early adherence of Candida albicans.

    PubMed

    Pan, Hong; Wang, Guomin; Pan, Jie; Ye, Guopin; Sun, Ke; Zhang, Jue; Wang, Jing

    2015-01-01

    Atmospheric-pressure cold plasma was applied to process the surface of heat-polymerized acrylic resin. Changes to the physical properties and early adherence of Candida albicans were investigated. Alternating current cold plasma with Ar/O2 as working gas was used. Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) were employed to study the possible mechanism. Experimental results showed that after plasma treatment, the contact angle of acrylic resin significantly decreased. There were no significant differences in roughness, flexural strength and elasticity modulus, but microhardness was significant improved in the treated group. More importantly, the early adherence of Candida albicans on the surface was reduced after plasma treatment. Cold plasma seemed to be a promising and convenient strategy of preventing the early adherence of Candida albicans on acrylic resins, which would greatly benefit potential dental applications.

  18. Endothelial Cell Injury Caused by Candida albicans Is Dependent on Iron

    PubMed Central

    Fratti, Rutilio A.; Belanger, Paul H.; Ghannoum, Mahmoud A.; Edwards, John E.; Filler, Scott G.

    1998-01-01

    Although it is known that Candida albicans causes endothelial cell injury, in vitro and in vivo, the mechanism by which this process occurs remains unknown. Iron is critical for the induction of injury in many types of host cells. Therefore, we investigated the role of iron in Candida-induced endothelial cell injury. We found that pretreatment of endothelial cells with the iron chelators phenanthroline and deferoxamine protected them from candidal injury, even though the organisms germinated and grew normally. Loading endothelial cells with iron reversed the cytoprotective effects of iron chelation. Moreover, chelation of endothelial cell iron significantly reduced phagocytosis of C. albicans by these cells, while candidal adherence to chelator-treated endothelial cells was slightly enhanced. Since endothelial cell phagocytosis of C. albicans is required for endothelial cell injury to occur, inhibition of phagocytosis is likely the principal mechanism of the cytoprotective effects of iron chelation. The production of toxic reactive oxygen intermediates by host cells is known to be inhibited by iron chelation. Therefore, we investigated whether treating endothelial cells with antioxidants could mimic the cytoprotective effects of iron chelation. Neither extracellular nor membrane-permeative antioxidants reduced candidal injury of endothelial cells. Furthermore, depleting endothelial cells of the endogenous antioxidant glutathione did not render them more susceptible to damage by C. albicans. These results suggest that candidal injury of endothelial cells is independent of the production of reactive oxygen intermediates and that the cytoprotective effects of iron chelation are not due to inhibition of the synthesis of these toxic intermediates. PMID:9423857

  19. Secretory Aspartyl Proteinases Cause Vaginitis and Can Mediate Vaginitis Caused by Candida albicans in Mice

    PubMed Central

    Pericolini, Eva; Gabrielli, Elena; Amacker, Mario; Kasper, Lydia; Roselletti, Elena; Luciano, Eugenio; Sabbatini, Samuele; Kaeser, Matthias; Moser, Christian; Hube, Bernhard; Vecchiarelli, Anna

    2015-01-01

    ABSTRACT Vaginal inflammation (vaginitis) is the most common disease caused by the human-pathogenic fungus Candida albicans. Secretory aspartyl proteinases (Sap) are major virulence traits of C. albicans that have been suggested to play a role in vaginitis. To dissect the mechanisms by which Sap play this role, Sap2, a dominantly expressed member of the Sap family and a putative constituent of an anti-Candida vaccine, was used. Injection of full-length Sap2 into the mouse vagina caused local neutrophil influx and accumulation of the inflammasome-dependent interleukin-1β (IL-1β) but not of inflammasome-independent tumor necrosis factor alpha. Sap2 could be replaced by other Sap, while no inflammation was induced by the vaccine antigen, the N-terminal-truncated, enzymatically inactive tSap2. Anti-Sap2 antibodies, in particular Fab from a human combinatorial antibody library, inhibited or abolished the inflammatory response, provided the antibodies were able, like the Sap inhibitor Pepstatin A, to inhibit Sap enzyme activity. The same antibodies and Pepstatin A also inhibited neutrophil influx and cytokine production stimulated by C. albicans intravaginal injection, and a mutant strain lacking SAP1, SAP2, and SAP3 was unable to cause vaginal inflammation. Sap2 induced expression of activated caspase-1 in murine and human vaginal epithelial cells. Caspase-1 inhibition downregulated IL-1β and IL-18 production by vaginal epithelial cells, and blockade of the IL-1β receptor strongly reduced neutrophil influx. Overall, the data suggest that some Sap, particularly Sap2, are proinflammatory proteins in vivo and can mediate the inflammasome-dependent, acute inflammatory response of vaginal epithelial cells to C. albicans. These findings support the notion that vaccine-induced or passively administered anti-Sap antibodies could contribute to control vaginitis. PMID:26037125

  20. Biofilms of Candida albicans serotypes A and B differ in their sensitivity to photodynamic therapy.

    PubMed

    Rossoni, Rodnei Dennis; Barbosa, Júnia Oliveira; de Oliveira, Felipe Eduardo; de Oliveira, Luciane Dias; Jorge, Antonio Olavo Cardoso; Junqueira, Juliana Campos

    2014-09-01

    Candida albicans is classified into different serotypes according to cell wall mannan composition and cell surface hydrophobicity. Since the effectiveness of photodynamic therapy (PDT) depends on the cell wall structure of microorganisms, the objective of this study was to compare the sensitivity of in vitro biofilms of C. albicans serotypes A and B to antimicrobial PDT. Reference strains of C. albicans serotype A (ATCC 36801) and serotype B (ATCC 36802) were used for the assays. A gallium-aluminum-arsenide laser (660 nm) was used as the light source and methylene blue (300 μM) as the photosensitizer. After biofilm formation on the bottom of a 96-well microplate for 48 h, each Candida strain was submitted to assays: PDT consisting of laser and photosensitizer application (L + P+), laser application alone (L + P-), photosensitizer application alone (L-P+), and application of saline as control (L-P-). After treatment, biofilm cells were scraped off and transferred to tubes containing PBS. The content of the tubes was homogenized, diluted, and seeded onto Sabouraud agar plates to determine the number of colony-forming units (CFU/mL). The results were compared by analysis of variance and Tukey test (p < 0.05). The two strains studied were sensitive to PDT (L + P+), with a log reduction of 0.49 for serotype A and of 2.34 for serotype B. Laser application alone only reduced serotype B cells (0.53 log), and the use of the photosensitizer alone had no effect on the strains tested. It can be concluded that in vitro biofilms of C. albicans serotype B were more sensitive to PDT.

  1. Modification of Surface Properties of Biomaterials Influences the Ability of Candida albicans To Form Biofilms

    PubMed Central

    Chandra, Jyotsna; Patel, Jasmine D.; Li, Jian; Zhou, Guangyin; Mukherjee, Pranab K.; McCormick, Thomas S.; Anderson, James M.; Ghannoum, Mahmoud A.

    2005-01-01

    Candida albicans biofilms form on indwelling medical devices (e.g., denture acrylic or intravenous catheters) and are associated with both oral and invasive candidiasis. Here, we determined whether surface modifications of polyetherurethane (Elasthane 80A [E80A]), polycarbonateurethane, and poly(ethyleneterephthalate) (PET) can influence fungal biofilm formation. Polyurethanes were modified by adding 6% polyethylene oxide (6PEO), 6% fluorocarbon, or silicone, while t