Molecular Aspect of Drug Resistance in Candida albicans Isolates of Women with Vulvovaginal Candidiasis

ABSTRACT Overexpression of CDR1, an efflux pump, is one of the major mechanisms contributing to drug resistance in Candida albicans. CDR1 p-lacZ was constructed and transformed into a Saccharomyces cerevisiae strain so that the lacZ gene could be used as the reporter to monitor the activity of the CDR1 promoter. Overexpression of CaNDT80, the C. albicans homolog of S. cerevisiae NDT80, increases the β-galactosidase activity of the CDR1 p-lacZ construct in S. cerevisiae. Furthermore, mutations in CaNDT80 abolish the induction of CDR1 expression by antifungal agents in C. albicans. Consistently, the Candt80/Candt80 mutant is also more susceptible to antifungal drugs than the wild-type strain. Thus, the gene for CaNdt80 may be the first gene among the regulatory factors involved in drug resistance in C. albicans whose function has been identified.

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Risks for Recurrent Vulvovaginal Candidiasis Caused by Non-Albicans Candida Versus Candida Albicans

Journal of Women s Health ◽

10.1089/jwh.2020.8811 ◽

2021 ◽

Author(s):

Andrea Boyd Tressler ◽

Metabel Markwei ◽

Chelsea Fortin ◽

Meng Yao ◽

Gary W. Procop ◽

...

Keyword(s):

Candida Albicans ◽

Vulvovaginal Candidiasis ◽

Recurrent Vulvovaginal Candidiasis

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Spilanthol as a promising antifungal alkylamide for the treatment of vulvovaginal candidiasis

Medical Mycology ◽

10.1093/mmy/myab054 ◽

2021 ◽

Author(s):

Rodrigo L Fabri ◽

Jhamine C O Freitas ◽

Ari S O Lemos ◽

Lara M Campos ◽

Irley O M Diniz ◽

...

Keyword(s):

Cell Wall ◽

Candida Albicans ◽

Antifungal Activity ◽

Cell Membrane ◽

Multidrug Resistant ◽

Fungal Strain ◽

Vulvovaginal Candidiasis ◽

Biofilm Matrix

Abstract Spilanthol is a bioactive alkylamide from the native Amazon plant species, Acmella oleracea. However, antifungal activities of spilanthol and its application to the therapeutic treatment of candidiasis remains to be explored. This study sought to evaluate the in vitro and in vivo antifungal activity of spilanthol previously isolated from A. oleracea (spilanthol(AcO)) against Candida albicans ATCC® 10231™, a multidrug-resistant fungal strain. Microdilution methods were used to determine inhibitory and fungicidal concentrations of spilanthol(AcO). In planktonic cultures, the fungal growth kinetics, yeast cell metabolic activity, cell membrane permeability and cell wall integrity were investigated. The effect of spilanthol(AcO) on the proliferation and adhesion of fungal biofilms was evaluated by whole slide imaging and scanning electron microscopy. The biochemical composition of the biofilm matrix was also analyzed. In parallel, spilanthol(AcO) was tested in vivo in an experimental vulvovaginal candidiasis model. Our in vitro analyses in C. albicans planktonic cultures detected a significant inhibitory effect of spilanthol(AcO), which affects both yeast cell membrane and cell wall integrity, interfering with the fungus growth. C. albicans biofilm proliferation and adhesion, as well as, carbohydrates and DNA in biofilm matrix were reduced after spilanthol(AcO) treatment. Moreover, infected rats treated with spilanthol(AcO) showed consistent reduction of both fungal burden and inflammatory processes compared to the untreated animals. Altogether, our findings demonstrated that spilanthol(AcO) is an bioactive compound against planktonic and biofilm forms of a multidrug resistant C. albicans strain. Furthermore, spilanthol(AcO) can be potentially considered for therapeutical treatment of vulvovaginal candidiasis caused by C. albicans. Lay Abstract This study sought to evaluate the antifungal activity of spilanthol against Candida albicans ATCC® 10 231™, a multidrug-resistant fungal strain. Our findings demonstrated that spilanthol(AcO) can be potentially considered for therapeutical treatment of vulvovaginal candidiasis caused by C. albicans.

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A conserved fungal hub protein involved in adhesion and drug resistance in the human pathogen Candida albicans

The Cell Surface ◽

10.1016/j.tcsw.2018.10.002 ◽

2018 ◽

Vol 4 ◽

pp. 10-19 ◽

Cited By ~ 1

Author(s):

Hélène Martin-Yken ◽

Tina Bedekovic ◽

Alexandra C. Brand ◽

Mathias L. Richard ◽

Sadri Znaidi ◽

...

Keyword(s):

Drug Resistance ◽

Candida Albicans ◽

Human Pathogen ◽

Human Pathogen Candida Albicans

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Role of Matrix β-1,3 Glucan in Antifungal Resistance of Non-albicans Candida Biofilms

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02378-12 ◽

2013 ◽

Vol 57 (4) ◽

pp. 1918-1920 ◽

Cited By ~ 68

Author(s):

K. F. Mitchell ◽

H. T. Taff ◽

M. A. Cuevas ◽

E. L. Reinicke ◽

H. Sanchez ◽

...

Keyword(s):

Health Care ◽

Drug Resistance ◽

Candida Albicans ◽

Care Setting ◽

Antifungal Susceptibility ◽

Antifungal Drug ◽

Content Type ◽

The Matrix ◽

Biofilm Matrix

ABSTRACTCandidabiofilm infections pose an increasing threat in the health care setting due to the drug resistance associated with this lifestyle. Several mechanisms underlie the resistance phenomenon. InCandida albicans, one mechanism involves drug impedance by the biofilm matrix linked to β-1,3 glucan. Here, we show this is important for otherCandidaspp. We identified β-1,3 glucan in the matrix, found that the matrix sequesters antifungal drug, and enhanced antifungal susceptibility with matrix β-1,3 glucan hydrolysis.

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Candida albicans exhibits distinct cytoprotective responses to anti-fungal drugs that facilitate the evolution of drug resistance

10.1101/2020.01.21.914549 ◽

2020 ◽

Cited By ~ 1

Author(s):

V Bettauer ◽

S Massahi ◽

S Khurdia ◽

ACBP Costa ◽

RP Omran ◽

...

Keyword(s):

Drug Resistance ◽

Candida Albicans ◽

Drug Exposure ◽

Fluorescent Imaging ◽

Late Time ◽

Transport Mechanisms ◽

Short Term ◽

Anti Fungal ◽

Initial Drug

AbstractWe developed a modified protocol for nanolitre droplet-based single cell sequencing appropriate for fungal settings, and used it to transcriptionally profiled several thousands cells from a prototrophic Candida albicans population and several drug exposed colonies (incl. fluconazole, caspofungin and nystatin). Thousands of cells from each colony were profiled both at early and late time points post-treatment in order to infer survival trajectories from initial drug tolerance to drug resistance. We find that prototrophic C. albicans populations differentially and stochastically express cytoprotective epigenetic programs. For all drugs, there is evidence that tolerant individuals partition into distinct subpopulations, each with a unique survival strategy involving different regulatory programs. These responses are weakly related to changes in morphology (shift from white to opaque forms, or shift from yeast to filamentous forms). In turn, those subpopulations that successfully reach resistance each have a distinct multivariate epigenetic response that coordinates the expression of efflux pumps, chaperones, transport mechanisms, and cell wall maintenance. Live cell fluorescent imaging was used to validate predictions of which molecular responses most often led to survival after drug exposure. Together our findings provide evidence that C. albicans has a robust toolkit of short-term epigenetic cytoprotective responses designed to “buy time” and increase the chance of acquiring long-term resistance.

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Evolution of Drug Resistance in Experimental Populations of Candida albicans

Journal of Bacteriology ◽

10.1128/jb.182.6.1515-1522.2000 ◽

2000 ◽

Vol 182 (6) ◽

pp. 1515-1522 ◽

Cited By ~ 124

Author(s):

Leah E. Cowen ◽

Dominique Sanglard ◽

David Calabrese ◽

Caroline Sirjusingh ◽

James B. Anderson ◽

...

Keyword(s):

Drug Resistance ◽

Candida Albicans ◽

Marker Genes ◽

Gene Encoding ◽

Fluconazole Resistance ◽

Genomic Changes ◽

Atp Binding Cassette Transporter ◽

Experimental Populations ◽

Major Facilitator ◽

Different Levels

ABSTRACT Adaptation to inhibitory concentrations of the antifungal agent fluconazole was monitored in replicated experimental populations founded from a single, drug-sensitive cell of the yeast Candida albicans and reared over 330 generations. The concentration of fluconazole was maintained at twice the MIC in six populations; no fluconazole was added to another six populations. All six replicate populations grown with fluconazole adapted to the presence of drug as indicated by an increase in MIC; none of the six populations grown without fluconazole showed any change in MIC. In all populations evolved with drug, increased fluconazole resistance was accompanied by increased resistance to ketoconazole and itraconazole; these populations contained ergosterol in their cell membranes and were amphotericin sensitive. The increase in fluconazole MIC in the six populations evolved with drug followed different trajectories, and these populations achieved different levels of resistance, with distinct overexpression patterns of four genes involved in azole resistance: the ATP-binding cassette transporter genes,CDR1 and CDR2; the gene encoding the target enzyme of the azoles in the ergosterol biosynthetic pathway,ERG11; and the major facilitator gene, MDR1. Selective sweeps in these populations were accompanied by additional genomic changes with no known relationship to drug resistance: loss of heterozygosity in two of the five marker genes assayed and alterations in DNA fingerprints and electrophoretic karyotypes. These results show that chance, in the form of mutations that confer an adaptive advantage, is a determinant in the evolution of azole drug resistance in experimental populations of C. albicans.

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Analysis of pathogenic factors of Candida albicans and the effect of vaginal immunization on recurrent vulvovaginal candidiasis in mice

Journal of Obstetrics and Gynaecology Research ◽

10.1111/jog.15140 ◽

2021 ◽

Author(s):

Ming‐Kun Shao ◽

Wen‐Jin Qi ◽

Meng‐Yao Hou ◽

Dan‐Dan Luo

Keyword(s):

Candida Albicans ◽

Vulvovaginal Candidiasis ◽

Recurrent Vulvovaginal Candidiasis ◽

Pathogenic Factors

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Different expression levels of ALS and SAP genes contribute to recurrent vulvovaginal candidiasis by Candida albicans

Future Microbiology ◽

10.2217/fmb-2020-0059 ◽

2021 ◽

Author(s):

Patrícia de S Bonfim-Mendonça ◽

Flávia K Tobaldini-Valério ◽

Isis RG Capoci ◽

Daniella R Faria ◽

Karina M Sakita ◽

...

Keyword(s):

Candida Albicans ◽

Hela Cells ◽

Gene Families ◽

Vulvovaginal Candidiasis ◽

Aspartic Proteinases ◽

Expression Levels ◽

Host Interactions ◽

Qrt Pcr ◽

Colony Forming Units ◽

Number Of Genes

Aim: To study the behavior of Candida albicans from women with vulvovaginal candidiasis (VVC), recurrent VVC (RVVC) and asymptomatic (AS), regarding adhesion on HeLa cells and their ability to express secreted aspartic proteinases ( SAP) genes, agglutinin like sequence ( ALS) genes and HWP1. Materials & methods: The adhesion of Candida albicans to HeLa cells was evaluated by colony-forming units, and the expressed genes were evaluated by qRT-PCR. Results: AS and VVC isolates showed greater ability to adhere HeLa cells when compared with RVVC isolate. Nevertheless, RVVC isolate exhibited upregulation of a large number of genes of ALS and SAP gene families and HWP1 gene. Conclusion: The results demonstrated that RVVC isolate expressed significantly important genes for invasion and yeast–host interactions.

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