Triazole phenotypes and genotypic characterization of clinical Aspergillus fumigatus isolates in China

Abstract

This study investigated the triazole phenotype and genotypic of clinical Aspergillus fumigatus isolates from China. We determined the triazole susceptibility profiles of 159 A. fumigatus isolates collected between 2011 and 2015 from four different areas in China tested against 10 antifungal drugs using the Clinical Laboratory Standard Institute M38-A2 method. For the seven itraconazole-resistant A. fumigatus isolates identified in the study, the cyp51A gene, including its promoter region, was sequenced and the mutation patterns were characterized. The resistant isolates were genotyped by microsatellite typing to determine the genetic relatedness to isolates from China and other countries. The frequency of itraconazole resistance in A. fumigatus isolates in our study was 4.4% (7/159). Six of the seven triazole-resistant isolates were recovered from the east and southeast of China, and one from was recovered from the west of China. No resistant isolates were found in the north. Three triazole-resistant isolates exhibited the TR₃₄/L98H mutation, two carried the TR₃₄/L98H/S297T/F495I mutation and one harbored a G54V mutation in the cyp51A gene. Analysis of the microsatellite markers from seven non-wild-type isolates indicated the presence of five unique genotypes, which clustered into two major genetic groups. The cyp51A gene mutations TR₃₄/L98H and TR₃₄/L98H/S297T were the most frequently found mutations, and the G54V mutation was reported for the first time in China. The geographic origin of the triazole-resistant isolates appeared to concentrate in eastern and south-eastern areas, which suggests that routine antifungal susceptibility testing in these areas should be performed for all clinically relevant A. fumigatus isolates to guide antifungal therapy and for epidemiological purposes.

Emerging Microbes & Infections (2017) 6, e109; doi:10.1038/emi.2017.97; published online 6 December

• antifungal susceptibility testing
• drug resistance
• drug target mutation
• epidemiology
• microsatellite markers
• triazole-resistant

Acknowledgments

This study was supported by the National Natural Science Foundation of China (81471926), the National Key Basic Research Program of China (2013CB531601 and 2013CB531606) and the Shanghai Municipal Natural Science Foundation (16ZR1432400 and 14DZ2272900). This publication was prepared as a collaborative study between the Department of Dermatology, Tongji Hospital of Tongji University, Tongji University School of Medicine, Shanghai, China and the Shanghai Institute of Medical Mycology, Changzheng Hospital, Second Military Medical University, Shanghai, China.

Supplementary Information for this article can be found on the Emerging Microbes & Infections website (http://www.nature.com/emi)