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

Abstract

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. 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.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 MIC, 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.Compratively & recovered in huge quantity from higher altitudes.Clinical break points for , & subsequently for terbinafine (11.9-21.6µg/ml), for Itraconazole(0.22-1.25µl/ml) & for Fluconazole (0.12-0.22µl/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. It is difficult to find out the impact of increased MIC directly but helpful in associated pharmacokinetics & pharmacodynamics by calculating C/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.