title: Epidemiology and Molecular Characterizations of Azole Resistance in Clinical and Environmental Aspergillus fumigatus Isolates from China.
abstract: 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.
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Dermatology Department, Tongji Hospital of Tongji University, Shanghai, China.
authors.forename: Jingjun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Clinical Laboratory, General Hospital of Chengdu Military Command, Chengdu, China.
authors.forename: Ziying
authors.initials: Z
authors.lastname: Zou
authors.affiliation: Department of Clinical Laboratory, General Hospital of Ji'nan Military Command, Ji'nan, China.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Clinical Laboratory, Chinese PLA 302 Hospital, Beijing, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Qu
authors.affiliation: Department of Respiratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhiyao
authors.initials: Z
authors.lastname: Bao
authors.affiliation: Department of Clinical Laboratory, Chinese PLA 202 Hospital, Shenyang, China.
authors.forename: Guangbin
authors.initials: G
authors.lastname: Qiu
authors.affiliation: Department of Clinical Laboratory, The Third Xiangya Hospital of Central South University, Changsha, China.
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Song
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Mandong
authors.initials: M
authors.lastname: Hu
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Xuelin
authors.initials: X
authors.lastname: Han
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Shuguang
authors.initials: S
authors.lastname: Tian
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Jingya
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Fangyan
authors.initials: F
authors.lastname: Chen
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Changjian
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Yansong
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Verweij
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China hanlicdc@163.com huangliuyuly@163.com.
authors.forename: Liuyu
authors.initials: L
authors.lastname: Huang
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China hanlicdc@163.com huangliuyuly@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Han
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D001393:Azoles / Q000494:pharmacology; D002681:China / Q000453:epidemiology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D025141:Drug Resistance, Fungal / Q000187:drug effects* / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics; D006801:Humans; D018895:Microsatellite Repeats; D010802:Phylogeny
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D005656:Fungal Proteins; D003577:Cytochrome P-450 Enzyme System; C465526:cytochrome P-450 CYP51A, Aspergillus