TRIAZOLE RESISTANCE IN ASPERGILLUS FUMIGATUS-A COMPREHENSIVE REVIEW

Abstract

Aspergillus fumigatus is a common ubiquitous fungal pathogen present in the environment including soil, decaying leaves, compost, grain crops and household dust. It can turn opportunistic in immunocompromised individuals causing allergic diseases, respiratory problems and invasive blood stream infections. Being saprophytic, it propagates by producing minute grey-green conidia that can become airborne and reach humans. In majority of cases, aspergillosis due to this organism can heal with treatment by antifungals. The azole compounds, one of the most important antifungal drugs, generally target the 14-α sterol demethylase enzyme, encoded by the cyp51A gene of the fungus, causing impaired membrane ergosterol synthesis. However in recent years the situation has turned grave due to development of azole resistant fungal species both in the environment as well as in the clinics. The main mechanism of resistance in A. fumigatus involves incorporation of tandem repeats in the promoter region of cyp51A, along with point mutations in the gene sequence. Resistant isolates tend to arise either due to excessive use of azole fungicides in the agricultural fields, from where they reach human through sporulation; or by prolonged treatment of patients with azole drugs. The early diagnosis of aspergillosis is very crucial for successful treatment of a patient. The article brings forth a comprehensive study of this organism, the mechanism of development and spread of azole resistant fungal isolates, genetic basis of development of azole resistance, detection of resistant strains and finally drugs used to combat the fungal infection.