Epidemiology and Molecular Characterizations of Azole Resistance in Clinical and Environmental Aspergillus fumigatus Isolates from China

Azole resistance in Aspergillus fumigatus has emerged as a worldwide public health problem. We sought here to demonstrate the occurrence and characteristics of azole resistance in A. fumigatus from different parts of China. A total of 317 clinical and 144 environmental A. fumigatus isolates from 12 provinces were collected and subjected to screening for azole resistance. Antifungal susceptibility, cyp51A gene sequencing, and genotyping were carried out for all suspected azole-resistant isolates and a subset of azole-susceptible isolates. As a result, 8 (2.5%) clinical and 2 (1.4%) environmental A. fumigatus isolates were identified as azole resistant. Five azole-resistant strains exhibit the TR34/L98H mutation, whereas four carry the TR34/L98H/S297T/F495I mutation in the cyp51A gene. Genetic typing and phylogenetic analysis showed that there was a worldwide clonal expansion of the TR34/L98H isolates, while the TR34/L98H/S297T/F495I isolates from China harbored a distinct genetic background with resistant isolates from other countries. High polymorphisms existed in the cyp51A gene that produced amino acid changes among azole-susceptible A. fumigatus isolates, with N248K being the most common mutation. These data suggest that the wide distribution of azole-resistant A. fumigatus might be attributed to the environmental resistance mechanisms in China.