Vacuolar proton-translocating ATPase is required for antifungal resistance and virulence of Candida glabrata

Aim: Melanin has been linked to pathogenesis in several fungi. They often produce melanin-like pigments in the presence of L-dihydroxyphenylalanine (L-DOPA), but this is poorly studied in Candida glabrata. Methods & materials: C. glabrata was grown in minimal medium with or without L-DOPA supplementation and submitted to a chemical treatment with denaturant and hot acid. Results: C. glabrata turned black when grown in the presence of L-DOPA, whereas cells grown without L-DOPA supplementation remained white. Biophysical properties demonstrated that the pigment was melanin. Melanized C. glabrata cells were effectively protected from azoles and amphotericin B, incubation at 42°C and macrophage killing. Conclusion: In the presence of L-DOPA, C. glabrata produces melanin, increases antifungal resistance and enhances host survival.

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Enhanced Efflux Pump Activity in OldCandida glabrataCells

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02227-17 ◽

2018 ◽

Vol 62 (3) ◽

Cited By ~ 8

Author(s):

Somanon Bhattacharya ◽

Bettina C. Fries

Keyword(s):

Amphotericin B ◽

Abc Transporters ◽

Resistant Strain ◽

Candida Glabrata ◽

Efflux Pump ◽

Antifungal Resistance ◽

Replicative Aging ◽

Glucan Synthase ◽

Content Type ◽

Pump Activity

ABSTRACTWe investigated the effect of replicative aging on antifungal resistance inCandida glabrata. Our studies demonstrate significantly increased transcription of ABC transporters and efflux pump activity in old versus youngC. glabratacells of a fluconazole-sensitive and -resistant strain. In addition, higher tolerance to killing by micafungin and amphotericin B was noted and is associated with higher transcription of glucan synthase geneFKS1and lower ergosterol content in older cells.

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Multilocus Sequence Typing (MLST) Genotypes of Candida glabrata Bloodstream Isolates in Korea: Association With Antifungal Resistance, Mutations in Mismatch Repair Gene (Msh2), and Clinical Outcomes

Frontiers in Microbiology ◽

10.3389/fmicb.2018.01523 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 16

Author(s):

Seung A. Byun ◽

Eun Jeong Won ◽

Mi-Na Kim ◽

Wee Gyo Lee ◽

Kyungwon Lee ◽

...

Keyword(s):

Mismatch Repair ◽

Clinical Outcomes ◽

Multilocus Sequence Typing ◽

Candida Glabrata ◽

Antifungal Resistance ◽

Mismatch Repair Gene ◽

Resistance Mutations ◽

Repair Gene

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Low level of antifungal resistance of Candida glabrata blood isolates in Turkey: Fluconazole minimum inhibitory concentration and FKS mutations can predict therapeutic failure

Mycoses ◽

10.1111/myc.13104 ◽

2020 ◽

Vol 63 (9) ◽

pp. 911-920 ◽

Cited By ~ 9

Author(s):

Amir Arastehfar ◽

Farnaz Daneshnia ◽

Mohammadreza Salehi ◽

Melike Yaşar ◽

Tuğrul Hoşbul ◽

...

Keyword(s):

Minimum Inhibitory Concentration ◽

Candida Glabrata ◽

Inhibitory Concentration ◽

Therapeutic Failure ◽

Antifungal Resistance ◽

Low Level

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Antifungal Resistance Pattern of Candida Species Isolated from High Vaginal Swabs of Women Attending a Hospital in Enugu State, Nigeria

Journal of Advances in Microbiology ◽

10.9734/jamb/2020/v20i930281 ◽

2020 ◽

pp. 62-72

Author(s):

Joachim Ohiakwu Ezeadila ◽

Ikechukwu Okoli ◽

Christie Amaechi Oyeka

Keyword(s):

Candida Albicans ◽

Amphotericin B ◽

Candida Tropicalis ◽

Candida Species ◽

Candida Glabrata ◽

Candida Parapsilosis ◽

Inhibition Zone ◽

Candida Krusei ◽

Antifungal Resistance ◽

Resistance Pattern

There is an increase in non-albicans Candida (NAC) vulvovaginal candidiasis which is attributed to overuse of antifungal therapy and this has led to antifungal resistance. This study was aimed at determining the antifungal resistance pattern of some clinical isolates of Candida species. Eighty-eight (88) isolates were used which included Candida tropicalis (34), Candida Parapsilosis (21), Candida albicans (20), Candida krusei (7) and Candida glabrata (6). The drugs used were Fluconazole (25µg), Ketoconazole (10µg), Voriconazole (1µg), Nystatin (100Units), Amphotericin B (20µg), Flucytosine (1µg), Clotrimazole (10µg) and Itraconazole (50µg). The susceptibility testing was carried out using the M44-A standard method for yeast disk diffusion testing. Results showed that the percentages of Candida species resistant to Fluconazole, Ketoconazole, Voriconazole, Amphotericin B, Flucytosine, Clotrimazole and Itraconazole and Nystatin were 52.3%, 61.9%, 35.2%, 19.3%, 86.4%, 34.1%, 45.5% and 44.3%, with inhibition zone diameters ≤14mm, ≤20mm, ≤13mm, <10mm, ≤11mm, ≤11mm, ≤13mm and no inhibition zone diameter respectively. Candida krusei was the most resistant species with 100% resistance to each of Fluconazole, Ketoconazole and Flucytosine. Candida tropicalis was the species with the highest susceptibility (79.4%) to Amphotericin B followed by Candida parapsilosis with inhibition zone diameters ≥15mm. While Candida glabrata showed 100% resistance to each of Flucytosine and Itraconazole, Candida albicans showed 100% resistance to Flucytosine only. Candida glabrata was the only Candida species with 0% resistance to Amphotericin B. The drug to which most of the Candida species were susceptible was Amphotericin B followed by Voriconazole while Flucytosine was the drug with the highest resistance followed by Ketoconazole and Fluconazole. The highest number of susceptible-dose dependent Candida isolates was observed with Ketoconazole (25%), followed by Clotrimazole and Itraconazole, each recording 23.9%. Based on the findings of the present study, Voriconazole is recommended for vaginal candidiasis especially in the study area and also especially for infections caused by Fluconazole-resistant Candida species. This suggests that routine sensitivity testing is pertinent to guiding the choice of antifungal therapy. Thus, indiscriminate use of antifungal drugs should be avoided to reduce the development and spread of resistance.

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