Analysis of different resistance mechanisms in cyp51 abc genes of panazole resistant aspergillus flavus clinical isolates from a tertiary care centre in India

Abstract

A flavus has emerged as a significant pathogen causing invasive and allergic infections particularly in tropical and subtropical areas of the world With the rise in the number of patients undergoing strong immunosuppression the incidence of invasive fungal infections has significantly increased over the past few decades The rise in azole resistance in this species poses a major clinical concern for effective treatment options The routinely used azoles and isavuconazole which is a newer azole also showed reduced in vitro activity in Aspergillus species To combat these fungal infections caused by Aspergillus species a detailed knowledge about the mechanism of azole antifungal resistance is much needed Being the second most common causative agent worldwide there is only limited data available for understanding the molecular mechanisms of resistance in A flavus All of these observations emphasizes the necessity for unveiling the mechanisms involved for developing better treatment strategy Among the conventional and newer azoles posaconazole and ravuconazole were found to be the most promising drugs Additionally luliconazole has shown versatile results in terms of its very low mean MIC against superficial otomycosis infections Also this study contributed new insights by uncovering novel substitutions in addition to the significant mutations that had been previously documented in cyp51A B C genes Pan azole resistance is more complex in filamentous fungi and in particular A flavus resistance is attributed to both gene expression and mutation newline