Page 46 - CSIR-IGIB Annual Report 2020-21

Emerging drug resistance in fungal skin naive cases and to terbinafine and fluconazole
infections in recalcitrant cases. To address the problem of
Dermatophytosis or invasion of keratinized resistance in naive and recalcitrant
tissue, (viz., skin, hair, and nails) by dermatophytosis, we have now carried out
dermatophytes is the most common superficial whole genome sequencing of 25 clinical fungal
fungal infection in the world, affecting ~25% of isolates. Variant mapping has been carried out
the world population at any given time. and shows that one of the terbinafine-resistant
Intervention methods to treat dermatophytosis T. rubrum strains in our collection harbors
are usually long-term, with several side-effects. nearly 2-fold more single nucleotide variations
Until recently, there have been no clinical (SNV) compared to strains from geographical
reports of generalized resistance to antifungal locations outside India. Distinct variations have
agents. Hence, the sudden emergence of a large also been mapped in key genes involved in drug
number of clinical cases that do not respond to response or its metabolism and their roles in
topical or systemic antifungal agents, from resistance confirmed by AFST. A transcriptome
different parts of the country, is alarming. We analysis of drug-resistant and drug-responder
have now set-up a multi-centric mini strains has helped map differential gene
consortium of clinicians from five different cities expression during drug challenge. Further, we
to investigate and address this sudden alarming are also simultaneously developing strategies,
increase in drug resistant fungi in India. including CRISPR-based methods to develop
Epidemiology of dermatophytosis over the past molecular tools for genetic manipulation of
3-4 years shows widespread reports of failure of filamentous fungi for validation studies. In
dermatophytes to administered antifungal conclusion, we have carried out whole genomic
agents. In our cross-sectional observational sequencing of the largest number of clinical
study of more than 200 cases of isolates of dermatophytes from any lab in India
dermatophytosis, a significant number of till date. Detailed comparative genomics
reinfected or recalcitrant cases were observed. analysis is ongoing and will help in better
Antifungal susceptibility tests (AFST) showed understanding, control, diagnosis, and
high MIC to terbinafine to be predominant in appropriate treatment of dermatophytosis.

Publications
Structural and thermodynamic characterization of a highly stable conformation of Rv2966c, a 16S rRNA
methyltransferase, at low pH. Khan SH, Bijpuria S, Maurya A, Taneja B. Int J Biol Macromol. 2020 Dec 1;164:3909-
3921.

Loss of U1498 methylation in 16S rRNA by RsmE methyltransferase associates its role with aminoglycoside
resistance in mycobacteria. Bijpuria S, Sharma R, Taneja B. J Glob Antimicrob Resist. 2020 Dec;23:359-369.
Terbinafine resistance in dermatophytes: Time to revisit alternate antifungal therapy. Gaurav V, Bhattacharya SN,
Sharma N, Datt S, Kumar P, Rai G, Singh PK, Taneja B, Das S. J Mycol Med. 2021 Mar;31(1):101087.

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