Study of squalene monooxygenase mutations in response to higher MIC range among four dermatophytes & their phylogenetic relatedness to Tinea indotineae at Doon valley

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Original Article

Author Details : Garima Sharma*, Daniel Alex Anand

Volume : 10, Issue : 4, Year : 2024

Article Page : 402-408

https://doi.org/10.18231/j.ijced.2024.071

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Abstract

Introduction: Antifungals reserved to, moderate & recurrent cases of mycosis. Allylamines considered as 1st line drugs & interfere with the ergosterol biosynthesis with SQLE gene. Strikingly elevated MIC leads to pathogen reassessment.
Aim & Objective: To find out species specific predominance, of dermatophytes, in demography of Uttarakhand. Their susceptibility range, molecular study; for mutations in squalene SQLE gene in relation to higher MIC & to corelate their phylogeny with previously reported genera.
Materials and Methods: Samples collected from public hospitals, including treatment failure & fresh cases, cultured at PDA for 25 days & identified under trinocular. Microdilution performed by EUCAST E.def 11 CLSI guidelines to calculate the MIC90, further genera confirmed by multiplying ITS1, ITS4,18s & 28s rRNA specific primers, followed by sequencing. Homology confirmed at NCBI-FASTA by preparing a cladogram by CLUSTAL W & MEGA X.
Results: Compratively Epidermophyton & Microsporum recovered in huge quantity from higher altitudes.  Clinical break points for Trichophyton, Epidermophyton & Microsporum subsequently for terbinafine (11.9-21.6g/ml), for Itraconazole(0.22-1.25l/ml) & for Fluconazole (0.12-0.22l/ml) found much multiplied than previously reported MIC, at all 3 altitudes. SQLE was modified at aa F397L, A448T in mentagrophyte & L393F in rubrum rRNA.
Conclusion: It is difficult to find out the impact of increased MIC directly but helpful in associated pharmacokinetics & pharmacodynamics by calculating Cmax /MIC, time of diffusion of drug & AUC/MIC ratios. PK/PD index in serum for increased MIC of antifungals more precisely to optimize antifungal therapy.

Keywords : MEGA X, CLUSTALW, Microdilution test, MIC, SQLE, PK/PD, Cladogram.

How to cite : Sharma G, Anand D A, Study of squalene monooxygenase mutations in response to higher MIC range among four dermatophytes & their phylogenetic relatedness to Tinea indotineae at Doon valley. IP Indian J Clin Exp Dermatol 2024;10(4):402-408

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