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Multiple origins of azole resistance in Aspergillus fumigatus in India

April 29 2016

Resistance to triazoles in A. fumigatus increases the probability that treatment will fail. Howard Chang et al. from McMaster University and colleagues from Delhi (2016) have found multiple origins for multi-triazole resistance in India. They analysed a total of 89 A. fumigatus isolates from India (51 multi-triazole resistant isolates, 38 azole-susceptible isolates). The study attempted to understand the origin, dispersal and long-term evolution of drug resistance in A. fumigatus. A combined analysis using multilocus sequence typing (MLST), Straf microsatellites and PCR fingerprinting found much more genetic variability than previously found in India. The development of resistance in environmental isolate 497/Ei/12/3, for example, was likely driven by agricultural fungicides, as it showed cross-resistance to those commonly used, including bromuconazole, tebuconazole and hexaconazole.  


Unexpectedly, one isolate (373/Ei/12/3) showed a sequence type different from the predominant clonal population using MLST markers, despite sharing the same microsatellite genotype. The opposite would normally be expected as the microsatellite method is known to have a higher discriminatory power than MLST analysis. Several possible explanations were discussed, including the emergence of these genotypes through sexual mating and allelic re-assortment.  In vitro, A. fumigatus is rather reluctant to undergo sex, but it may be more common in the environment (O'Gorman).


The genetic variation observed amongst the resistant A. fumigatus isolates has implications for the management of this pathogen within India, specifically as it relates to the overuse of triazoles in agriculture. Azole antifungals are the recommended first-line drugs in the treatment and prophylaxis of aspergillosis. There is a high burden of tuberculosis in India and Africa, and an estimated 290,000 patients with chronic aspergillosis (Agarwal). Allergic bronchopulmonary aspergillosis (ABPA) is also common in India, with an estimated 1.3 million affected (Agarwal). The high frequency of environmental isolates harbouring azole resistance therefore poses a significant therapeutic challenge. 


Original source: Chang et al. 2016

O'Gorman, Fuller & Dyer, 2009

Agarwal, Denning & Chakrabarti, 2014