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Assessment of antifungal resistance and associated molecular mechanism in Candida albicans isolates from different cohorts of patients in North Indian state of Haryana

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Abstract

The present study examines the trend in distribution of Candida species and their antifungal resistance patterns in hospitals across Haryana, a North Indian state with poorly addressed epidemiology of fungal infections. In our collection of 228 Candida isolates, Candida albicans dominated in both high vaginal swab (HVS) and urine samples while Candida glabrata and Candida tropicalis were the second-highest non-albicans Candida species (NAC), respectively. Of note, in blood samples, C. tropicalis and C. albicans were present in equal numbers. All 228 isolates were subjected to antifungal susceptibility tests, whereby 51% of C. albicans recovered from HVS samples displayed fluconazole resistance. To understand its mechanistic basis, expression profiling of efflux pump genes CDR1, CDR2, MDR1 and azole drug target, ERG11 was performed in 20 randomly selected resistant isolates, wherein many isolates elicited higher expression. Further, ERG11 gene sequencing suggested that most of the isolates harbored mutations, which are not reported with azole resistance. However, one isolate, RPCA9 (MIC 64 μg/mL) harbored triple mutation (Y132C, F145L, A114V), wherein Y132 and F145 sites were previously implicated in azole resistance. Interestingly, one isolate, (RPCA61) having MIC > 128 μg/mL harbored a novel mutation, G129R. Of note, HVS isolates RPCA 21, RPCA 22, and RPCA 44 (MICs 64 to > 128 μg/mL) did not show any change in alteration in ERG11 or overexpression of efflux pump genes. Together, this study presents a first report of Candida infections in selected hospitals of Haryana State.

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Abbreviations

HVS:

High vaginal swab

NAC:

Non-albicans Candida

RT-PCR:

Reverse transcriptase polymerase chain reaction

YEPD:

Yeast Extract Peptone Dextrose

SDA:

Sabouraud dextrose agar

BAL:

Bronchoalveolar lavage

CSF:

Cerebrospinal fluid

VVC:

Vulvo-vaginal candidiasis

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Acknowledgments

AKY would like to acknowledge Garima Shahi and Suman Sharma for their insightful suggestions and help during the course of the work.

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Contributions

RP and AK conceived the ideas. AK and RB collected the data. AK, RN, and MK performed the RT-PCR experiment. AK, RN, AB, and SMR analyzed the data. RP, AC, AK, RN, and AB wrote the manuscript with inputs from AKM and NAG.

Corresponding author

Correspondence to Rajendra Prasad.

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The authors confirm that the ethical policies of the journal, as noted on the journal’s author guidelines page, have been adhered to. No ethical approval was required for this article.

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The authors declare that they have no conflict of interest.

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Kumar, A., Nair, R., Kumar, M. et al. Assessment of antifungal resistance and associated molecular mechanism in Candida albicans isolates from different cohorts of patients in North Indian state of Haryana. Folia Microbiol 65, 747–754 (2020). https://doi.org/10.1007/s12223-020-00785-6

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  • DOI: https://doi.org/10.1007/s12223-020-00785-6

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