scholarly journals EFG1 Mutations, Phenotypic Switching, and Colonization by Clinical a/α Strains of Candida albicans

mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Yang-Nim Park ◽  
Kayla Conway ◽  
Claude Pujol ◽  
Karla J. Daniels ◽  
David R. Soll
Keyword(s):  
Candida Albicans ◽  
Microscopic Analysis ◽  
Great Majority ◽  
Phenotypic Switching ◽  
Live Cells ◽  
Content Type ◽  
Dominant Phenotype ◽  
Colonization Model ◽  
The One ◽  
Model Support

ABSTRACT The transcription factor EFG1 functions as a suppressor of white-to-opaque and white-to-gray switching in a/α strains of Candida albicans. In a collection of 27 clinical isolates, 4 of the 17 EFG1/EFG1 strains, 1 of the 2 EFG1/efg1 strains, and all 8 of the efg1/efg1 strains underwent white-to-opaque switching. The four EFG1/EFG1 strains, the one EFG1/efg1 strain, and one of the eight efg1/efg1 strains that underwent switching to opaque did not switch to gray and could not be complemented with a copy of EFG1. Competition experiments in a mouse model for gastrointestinal (GI) colonization confirmed that efg1/efg1 cells rapidly outcompete EFG1/EFG1 cells, and in plating experiments, formed colonies containing both gray and opaque cells. Direct microscopic analysis of live cells in the feces, however, revealed that the great majority of cells were opaque, suggesting opaque, not gray, may be the dominant phenotype at the site of colonization. IMPORTANCE Close to half of a collection of 27 clinical a/α isolates of Candida albicans underwent white-to-opaque switching. Complementation experiments revealed that while approximately half of the a/α switchers were due to EFG1 mutations, the remaining half were due to mutations in other genes. In addition, the results of competition experiments in a mouse GI tract colonization model support previous observations that efg1/efg1 cells rapidly outcompete EFG1/EFG1 strains, but direct microscopic analysis reveals that the major colonizing cells were opaque, not gray.

scholarly journals Identification of a Cell Death Pathway in Candida albicans during the Response to Pheromone

2010 ◽  
Vol 9 (11) ◽  
pp. 1690-1701 ◽  
Author(s):  
Kevin Alby ◽  
Dana Schaefer ◽  
Racquel Kim Sherwood ◽  
Stephen K. Jones ◽  
Richard J. Bennett
Keyword(s):  
Cell Death ◽  
Candida Albicans ◽  
Laboratory Strain ◽  
Opportunistic Pathogen ◽  
Cell Types ◽  
Yeast Cells ◽  
Phenotypic Switching ◽  
Morphological Response ◽  
Content Type ◽  
Cell Death Pathway

ABSTRACT Mating in hemiascomycete yeasts involves the secretion of pheromones that induce sexual differentiation in cells of the opposite mating type. Studies in Saccharomyces cerevisiae have revealed that a subpopulation of cells experiences cell death during exposure to pheromone. In this work, we tested whether the phenomenon of pheromone-induced death (PID) also occurs in the opportunistic pathogen Candida albicans. Mating in C. albicans is uniquely regulated by white-opaque phenotypic switching; both cell types respond to pheromone, but only opaque cells undergo the morphological transition and cell conjugation. We show that approximately 20% of opaque cells, but not white cells, of laboratory strain SC5314 experience pheromone-induced death. Furthermore, analysis of mutant strains revealed that PID was significantly reduced in strains lacking Fig1 or Fus1 transmembrane proteins that are induced during the mating process and, we now show, are necessary for efficient mating in C. albicans. The level of PID was also Ca2+ dependent, as chelation of Ca2+ ions increased cell death to almost 50% of the population. However, in contrast to S. cerevisiae PID, pheromone-induced killing of C. albicans cells was largely independent of signaling via the Ca2+-dependent protein phosphatase calcineurin, even when combined with the loss of Cmk1 and Cmk2 proteins. Finally, we demonstrate that levels of PID vary widely between clinical isolates of C. albicans, with some strains experiencing close to 70% cell death. We discuss these findings in light of the role of prodeath and prosurvival pathways operating in yeast cells undergoing the morphological response to pheromone.

scholarly journals The Human Gut Microbial Metabolome Modulates Fungal Growth via the TOR Signaling Pathway

mSphere ◽  
2017 ◽  
Vol 2 (6) ◽  
Author(s):  
Carlos García ◽  
Faiza Tebbji ◽  
Michelle Daigneault ◽  
Ning-Ning Liu ◽  
Julia R. Köhler ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Inflammatory Diseases ◽  
Opportunistic Pathogen ◽  
Convincing Evidence ◽  
Commensal Bacteria ◽  
Bioactive Molecules ◽  
Mucosal Barrier ◽  
Content Type ◽  
Bowel Diseases ◽  
The One

ABSTRACT Candida albicans is a natural component of the human microbiota but also an opportunistic pathogen that causes life-threatening infections. The human gastrointestinal tract is the main reservoir of C. albicans, from where systemic infections originate as a consequence of the disruption of the intestinal mucosal barrier. Recent studies provided convincing evidence that overgrowth of C. albicans and other related species in the gut is predominantly associated with chronic intestinal inflammatory bowel diseases. Here, we showed, for the first time, the antagonistic interkingdom interactions between C. albicans and common intestinal commensal bacteria. From a therapeutic perspective, administering a defined bacterial community, such as the one described here with anti-Candida activity, could provide potential therapeutic protection against gastrointestinal inflammatory diseases. Candida albicans is well known as a major human fungal pathogen, but it is also a permanent resident of healthy gastrointestinal tracts. Recent studies have shown that the human gut microbial metabolome represents an interesting source of bioactive molecules with a significant degree of chemical diversity. Some of these bioactive molecules may have useful antivirulence activities. For instance, intestinal bacterial species belonging to the Lachnospiraceae family were found to secrete molecules that attenuate Salmonella pathogenicity and repress the expression of virulence genes. Here, we have investigated whether the microbial gut metabolome (GM) contains molecules that might promote the commensal lifestyle and/or inhibit the expression of virulence of C. albicans in the intestine. We found that metabolites from human feces inhibited the growth of C. albicans and other opportunistic yeasts. A genetic screen in C. albicans suggested that TOR is the molecular target of the antifungal molecule(s) of the GM. In addition, we found that the GM metabolites inhibit both C. albicans hyphal growth and the invasion of human enterocytes. The antigrowth and antivirulence activities were partially recapitulated by secretions from Roseburia spp. and Bacteroides ovatus strains, respectively. This study demonstrates that the antimicrobial activity of the GM can be extended to a eukaryotic pathogen, C. albicans, illuminating the antagonistic interkingdom interactions between a fungus and intestinal commensal bacteria. IMPORTANCE Candida albicans is a natural component of the human microbiota but also an opportunistic pathogen that causes life-threatening infections. The human gastrointestinal tract is the main reservoir of C. albicans, from where systemic infections originate as a consequence of the disruption of the intestinal mucosal barrier. Recent studies provided convincing evidence that overgrowth of C. albicans and other related species in the gut is predominantly associated with chronic intestinal inflammatory bowel diseases. Here, we showed, for the first time, the antagonistic interkingdom interactions between C. albicans and common intestinal commensal bacteria. From a therapeutic perspective, administering a defined bacterial community, such as the one described here with anti-Candida activity, could provide potential therapeutic protection against gastrointestinal inflammatory diseases.

scholarly journals Improved Gene Ontology Annotation for Biofilm Formation, Filamentous Growth, and Phenotypic Switching in Candida albicans

2012 ◽  
Vol 12 (1) ◽  
pp. 101-108 ◽  
Author(s):  
Diane O. Inglis ◽  
Marek S. Skrzypek ◽  
Martha B. Arnaud ◽  
Jonathan Binkley ◽  
Prachi Shah ◽  
...  
Keyword(s):  
Gene Ontology ◽  
Candida Albicans ◽  
Gene Product ◽  
Fungal Pathogen ◽  
Biofilm Formation ◽  
Filamentous Growth ◽  
Phenotypic Switching ◽  
Gene Products ◽  
Content Type ◽  
Opportunistic Fungal Pathogen

ABSTRACTThe opportunistic fungal pathogenCandida albicansis a significant medical threat, especially for immunocompromised patients. Experimental research has focused on specific areas ofC. albicansbiology, 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 theCandidaGenome 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 inCandidaspecies, 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 otherCandidaspecies. Through genome annotation and analysis, we identified candidate pathogenicity genes in seven non-C. albicans Candidaspecies and in one additionalC. albicansstrain, WO-1. We also defined a set ofC. albicansgenes 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.

scholarly journals Candida albicans CUG Mistranslation Is a Mechanism To Create Cell Surface Variation

mBio ◽  
2013 ◽  
Vol 4 (4) ◽  
Author(s):  
Isabel Miranda ◽  
Ana Silva-Dias ◽  
Rita Rocha ◽  
Rita Teixeira-Santos ◽  
Carolina Coelho ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Cell Surface ◽  
Fungal Pathogen ◽  
Single Gene ◽  
Yeast Cells ◽  
Phenotypic Switching ◽  
Leucine Incorporation ◽  
Host Immune System ◽  
Content Type ◽  
Human Fungal Pathogen

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. IMPORTANCE The translation of genetic information into proteins is a highly accurate cellular process. In the human fungal pathogen Candida albicans, a unique mistranslation event involving the CUG codon occurs. The CUG codon is mainly translated as serine but can also be translated as leucine. Leucine and serine are two biochemically distinct amino acids, hydrophobic and hydrophilic, respectively. The increased rate of leucine incorporation at CUG decoding triggers C. albicans virulence attributes, such as morphogenesis, phenotypic switching, and adhesion. Here, we show that CUG mistranslation masks the fungal cell wall molecule β-glucan that is normally recognized by the host immune system, delaying its response. Furthermore, we demonstrate that two different proteins of the adhesin Als3 generated by CUG mistranslation confer increased hydrophobicity and adhesion ability on yeast cells. Thus, CUG mistranslation functions as a mechanism to create protein diversity with differential activities, constituting an advantage for a mainly asexual microorganism. This could explain its preservation during evolution.

scholarly journals pH Regulates White-Opaque Switching and Sexual Mating in Candida albicans

2015 ◽  
Vol 14 (11) ◽  
pp. 1127-1134 ◽  
Author(s):  
Yuan Sun ◽  
Chengjun Cao ◽  
Wei Jia ◽  
Li Tao ◽  
Guobo Guan ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Cell Formation ◽  
Culture Conditions ◽  
Phenotypic Switching ◽  
Acidic Ph ◽  
Ph Sensing ◽  
Content Type ◽  
Ph Changes ◽  
Wide Range ◽  
Sexual Mating

ABSTRACTAs a successful commensal and pathogen of humans,Candida albicansencounters a wide range of environmental conditions. Among them, ambient pH, which changes frequently and affects many biological processes in this species, is an important factor, and the ability to adapt to pH changes is tightly linked with pathogenesis and morphogenesis. In this study, we report that pH has a profound effect on white-opaque switching and sexual mating inC. albicans. Acidic pH promotes white-to-opaque switching under certain culture conditions but represses sexual mating. The Rim101-mediated pH-sensing pathway is involved in the control of pH-regulated white-opaque switching and the mating response. Phr2 and Rim101 could play a major role in acidic pH-induced opaque cell formation. Despite the fact that the cyclic AMP (cAMP) signaling pathway does not play a major role in pH-regulated white-opaque switching and mating, white and opaque cells of thecyr1/cyr1mutant, which is defective in the production of cAMP, showed distinct growth defects under acidic and alkaline conditions. We further discovered that acidic pH conditions repressed sexual mating due to the failure of activation of the Ste2-mediated α-pheromone response pathway in opaqueacells. The effects of pH changes on phenotypic switching and sexual mating could involve a balance of host adaptation and sexual reproduction inC. albicans.

How Phillips saw the light

2020 ◽  
Vol 36 (8) ◽  
pp. 29-31
Keyword(s):  
Design Methodology ◽  
Reading Time ◽  
Daily Basis ◽  
Business World ◽  
Content Type ◽  
Freak Show ◽  
The World ◽  
Pertinent Information ◽  
The One ◽  
Practical Implications

Purpose Reviews the latest management developments across the globe and pinpoints practical implications from cutting-edge research and case studies. Design/methodology/approach This briefing is prepared by an independent writer who adds their own impartial comments and places the articles in context. Findings The problem with developing a reputation of being something of an oracle in the business world is that all of a sudden, everyone expects you to pull off the trick of interpreting the future on a daily basis. Like a freak show circus act or one-hit wonder pop singer, people expect you to perform when they see you, and they expect you to perform the thing that made you famous, even if it is the one thing in the world you don’t want to do. And when you fail to deliver on these heightened expectations, you are dismissed as a one trick pony, however good that trick is in the first place. Originality/value The briefing saves busy executives and researchers hours of reading time by selecting only the very best, most pertinent information and presenting it in a condensed and easy-to-digest format.

PROMETHEE-based ranking of project managers based on the five personality traits

Kybernetes ◽  
2019 ◽  
Vol 49 (4) ◽  
pp. 1083-1102
Author(s):  
Georgios N. Aretoulis ◽  
Jason Papathanasiou ◽  
Fani Antoniou
Keyword(s):  
Personality Traits ◽  
Questionnaire Survey ◽  
Multicriteria Decision Making ◽  
Project Managers ◽  
Preference Ranking ◽  
Infrastructure Projects ◽  
Public Infrastructure ◽  
Content Type ◽  
The One ◽  
Selection Of

Purpose This paper aims to rank and identify the most efficient project managers (PMs) based on personality traits, using Preference Ranking Organization METHod for Enrichment Evaluations (PROMETHEE) methodology. Design/methodology/approach The proposed methodology relies on the five personality traits. These were used as the selection criteria. A questionnaire survey among 82 experienced engineers was used to estimate the required weights per personality trait. A second two-part questionnaire survey aimed at recording the PMs profile and assess the performance of personality traits per PM. PMs with the most years of experience are selected to be ranked through Visual PROMETHEE. Findings The findings suggest that a competent PM is the one that scores low on the “Neuroticism” trait and high especially on the “Conscientiousness” trait. Research limitations/implications The research applied a psychometric test specifically designed for Greek people. Furthermore, the proposed methodology is based on the personality characteristics to rank the PMs and does not consider the technical skills. Furthermore, the type of project is not considered in the process of ranking PMs. Practical implications The findings could contribute in the selection of the best PM that maximizes the project team’s performance. Social implications Improved project team communication and collaboration leading to improved project performance through better communication and collaboration. This is an additional benefit for the society, especially in the delivery of public infrastructure projects. A lot of public infrastructure projects deviate largely as far as cost and schedule is concerned and this is an additional burden for public and society. Proper project management through efficient PMs would save people’s money and time. Originality/value Identification of the best PMbased on a combination of multicriteria decision-making and psychometric tests, which focus on personality traits.

scholarly journals In VitroAnalyses of the Effects of Heparin and Parabens on Candida albicans Biofilms and Planktonic Cells

2011 ◽  
Vol 56 (1) ◽  
pp. 148-153 ◽  
Author(s):  
Marisa H. Miceli ◽  
Stella M. Bernardo ◽  
T. S. Neil Ku ◽  
Carla Walraven ◽  
Samuel A. Lee
Keyword(s):  
Candida Albicans ◽  
Metabolic Activity ◽  
Biofilm Formation ◽  
High Dose ◽  
Dependent Manner ◽  
Planktonic Cells ◽  
Content Type ◽  
Heparin Sodium ◽  
The Individual

ABSTRACTInfections and thromboses are the most common complications associated with central venous catheters. Suggested strategies for prevention and management of these complications include the use of heparin-coated catheters, heparin locks, and antimicrobial lock therapy. However, the effects of heparin onCandida albicansbiofilms and planktonic cells have not been previously studied. Therefore, we sought to determine thein vitroeffect of a heparin sodium preparation (HP) on biofilms and planktonic cells ofC. albicans. Because HP contains two preservatives, methyl paraben (MP) and propyl paraben (PP), these compounds and heparin sodium without preservatives (Pure-H) were also tested individually. The metabolic activity of the mature biofilm after treatment was assessed using XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction and microscopy. Pure-H, MP, and PP caused up to 75, 85, and 60% reductions of metabolic activity of the mature preformedC. albicansbiofilms, respectively. Maximal efficacy against the mature biofilm was observed with HP (up to 90%) compared to the individual compounds (P< 0.0001). Pure-H, MP, and PP each inhibitedC. albicansbiofilm formation up to 90%. A complete inhibition of biofilm formation was observed with HP at 5,000 U/ml and higher. When tested against planktonic cells, each compound inhibited growth in a dose-dependent manner. These data indicated that HP, MP, PP, and Pure-H havein vitroantifungal activity againstC. albicansmature biofilms, formation of biofilms, and planktonic cells. Investigation of high-dose heparin-based strategies (e.g., heparin locks) in combination with traditional antifungal agents for the treatment and/or prevention ofC. albicansbiofilms is warranted.

scholarly journals Novel Aggregation Properties of Candida albicans Secreted Aspartyl Proteinase Sap6 Mediate Virulence in Oral Candidiasis

2015 ◽  
Vol 83 (7) ◽  
pp. 2614-2626 ◽  
Author(s):  
Rohitashw Kumar ◽  
Darpan Saraswat ◽  
Swetha Tati ◽  
Mira Edgerton
Keyword(s):  
Candida Albicans ◽  
Epithelial Cells ◽  
Oral Candidiasis ◽  
Oral Microbiome ◽  
Proteinase Activity ◽  
Adhesion Properties ◽  
Content Type ◽  
Oral Epithelial Cells ◽  
Oral Epithelial ◽  
Cell Cell

Candida albicans, a commensal fungus of the oral microbiome, causes oral candidiasis in humans with localized or systemic immune deficiencies. Secreted aspartic proteinases (Saps) are a family of 10 related proteases and are virulence factors due to their proteolytic activity, as well as their roles in adherence and colonization of host tissues. We found that mice infected sublingually withC. albicanscells overexpressing Sap6 (SAP6OE and a Δsap8strain) had thicker fungal plaques and more severe oral infection, while infection with the Δsap6strain was attenuated. These hypervirulent strains had highly aggregative colony structurein vitroand higher secreted proteinase activity; however, the levels of proteinase activity ofC. albicansSaps did not uniformly match their abilities to damage cultured oral epithelial cells (SCC-15 cells). Hyphal induction in cells overexpressing Sap6 (SAP6OE and Δsap8cells) resulted in formation of large cell-cell aggregates. These aggregates could be produced in germinated wild-type cells by addition of native or heat-inactivated Sap6. Sap6 bound only to germinated cells and increasedC. albicansadhesion to oral epithelial cells. The adhesion properties of Sap6 were lost upon deletion of its integrin-binding motif (RGD) and could be inhibited by addition of RGD peptide or anti-integrin antibodies. Thus, Sap6 (but not Sap5) has an alternative novel function in cell-cell aggregation, independent of its proteinase activity, to promote infection and virulence in oral candidiasis.

scholarly journals Ultrafiltration Process in Disinfection and Advanced Treatment of Tertiary Treated Wastewater

Membranes ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 221
Author(s):  
Rafał Tytus Bray ◽  
Katarzyna Jankowska ◽  
Eliza Kulbat ◽  
Aneta Łuczkiewicz ◽  
Aleksandra Sokołowska
Keyword(s):  
Wastewater Treatment ◽  
Wastewater Treatment Plants ◽  
Microscopic Analysis ◽  
Fecal Coliforms ◽  
Treated Wastewater ◽  
Chemical Parameters ◽  
Virus Particles ◽  
E Coli ◽  
The One ◽  
Physical And Chemical

The paper presents the results of research on the use of ultrafiltration, using membranes of 200 and 400 kDa separation, for disinfection of municipal treated wastewater. The research was conducted on a fractional technical scale using real municipal treated wastewater from two large wastewater treatment plants treating most of the wastewater over the one-million polycentric Gdańsk agglomeration (1.2 million inhabitants). UF 200 kDa and UF 400 kDa processes enabled further improvement of the physical and chemical parameters of treated wastewater. Total phosphorus (to below 0.2 mg/L–UF 200 kDa, 0.13 mg/L–UF 400 kDa) and turbid substances (to below 0.2 mg/L, both membranes) were removed in the highest degree. COD was reduced efficiently (to below 25.6 mgO2/L–UF 200 kDa, 26.8 mgO2/L–UF 400 kDa), while total nitrogen was removed to a small extent (to 7.12 mg/L–UF 200 kDa and 5.7 mg/L–UF 400 kDa. Based on the reduction of indicator bacteria; fecal coliforms including E. coli (FC) and fecal enterococci (FE) it was found that the ultrafiltration is an effective method of disinfection. Not much indicator bacterial were observed in the permeate after processes (UF 200 kDa; FC—5 CFU/L; FE—1 CFU/L and UF 400 kDa; FC—70 CFU/L; FE—10 CFU/L. However, microscopic analysis of prokaryotic cells and virus particles showed their presence after the application of both membrane types; TCN 3.0 × 102 cells/mL–UF 200 kDa, 5.0 × 103 cells/mL–UF 400 kDa, VP 1.0 × 105/mL. The presence of potentially pathogenic, highly infectious virus particles means that ultrafiltration cannot be considered a sufficient disinfection method for treated wastewater diverted for reuse or discharged from high load wastewater treatment plants to recreational areas. For full microbiological safety it would be advisable to apply an additional disinfection method (e.g., ozonation).

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