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

被引:79
作者
Chen, Yong [1 ]
Lu, Zhongyi [1 ]
Zhao, Jingjun [2 ]
Zou, Ziying [3 ]
Gong, Yanwen [4 ]
Qu, Fen [5 ]
Bao, Zhiyao [6 ]
Qiu, Guangbin [7 ]
Song, Mingsheng [8 ]
Zhang, Qing [1 ]
Liu, Lin [1 ]
Hu, Mandong [1 ]
Han, Xuelin [1 ]
Tian, Shuguang [1 ]
Zhao, Jingya [1 ]
Chen, Fangyan [1 ]
Zhang, Changjian [1 ]
Sun, Yansong [1 ]
Verweij, Paul E. [9 ]
Huang, Liuyu [1 ]
Han, Li [1 ]
机构
[1] Acad Mil Med Sci, Inst Dis Control & Prevent, Beijing, Peoples R China
[2] Tongji Univ, Tongji Hosp, Dept Dermatol, Shanghai, Peoples R China
[3] Gen Hosp Chengdu Mil Command, Dept Clin Lab, Chengdu, Peoples R China
[4] Gen Hosp Jinan Mil Command, Dept Clin Lab, Jinan, Peoples R China
[5] Chinese PLA 302 Hosp, Dept Clin Lab, Beijing, Peoples R China
[6] Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Resp Med, Shanghai, Peoples R China
[7] Chinese PLA 202 Hosp, Dept Clin Lab, Shenyang, Peoples R China
[8] Cent S Univ, Xiangya Hosp 3, Dept Clin Lab, Changsha, Hunan, Peoples R China
[9] Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, Nijmegen, Netherlands
关键词
CYP51A GENE; TR46/Y121F/T289A MUTATION; TR34/L98H MUTATIONS; CYSTIC-FIBROSIS; HIGH PREVALENCE; EMERGENCE; SUSCEPTIBILITY; IDENTIFICATION; MANAGEMENT; MECHANISM;
D O I
10.1128/AAC.01005-16
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 azolesusceptible 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.
引用
收藏
页码:5878 / 5884
页数:7
相关论文
共 46 条
[1]   Concomitant occurrence of itraconazole-resistant and -susceptible strains of Aspergillus fumigatus in routine cultures [J].
Ahmad, Suhail ;
Joseph, Leena ;
Hagen, Ferry ;
Meis, Jacques F. ;
Khan, Ziauddin .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2015, 70 (02) :412-415
[2]  
Al-WathiqiAhmad S, 2014, ENV RES C, V133C, P20
[3]  
Arendrup MC, 2015, EDEF93 EUR COMM ANT
[4]   First Detection of TR46/Y121F/T289A and TR34/L98H Alterations in Aspergillus fumigatus Isolates from Azole-Naive Patients in Denmark despite Negative Findings in the Environment [J].
Astvad, K. M. T. ;
Jensen, R. H. ;
Hassan, T. M. ;
Mathiasen, E. G. ;
Thomsen, G. M. ;
Pedersen, U. G. ;
Christensen, M. ;
Hilberg, O. ;
Arendrup, M. C. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2014, 58 (09) :5096-5101
[5]   Environmental study of azole-resistant Aspergillus fumigatus with TR34/L98H mutations in the cyp51A gene in Iran [J].
Badali, Hamid ;
Vaezi, Afsane ;
Haghani, Iman ;
Yazdanparast, Seyed A. ;
Hedayati, Mohammad T. ;
Mousavi, Bita ;
Ansari, Saham ;
Hagen, Ferry ;
Meis, Jacques F. ;
Chowdhary, Anuradha .
MYCOSES, 2013, 56 (06) :659-663
[6]   Aspergillus lentulus sp nov., a new sibling species of A-fumigatus [J].
Balajee, SA ;
Gribskov, JL ;
Hanley, E ;
Nickle, D ;
Marr, KA .
EUKARYOTIC CELL, 2005, 4 (03) :625-632
[7]   Molecular Epidemiology of Aspergillus fumigatus Isolates Harboring the TR34/L98H Azole Resistance Mechanism [J].
Camps, Simone M. T. ;
Rijs, Antonius J. M. M. ;
Klaassen, Corne H. W. ;
Meis, Jacques F. ;
O'Gorman, Celine M. ;
Dyer, Paul S. ;
Melchers, Willem J. G. ;
Verweij, Paul E. .
JOURNAL OF CLINICAL MICROBIOLOGY, 2012, 50 (08) :2674-2680
[8]   Emergence of TR46/Y121F/T289A in an Aspergillus fumigatus Isolate from a Chinese Patient [J].
Chen, Yong ;
Wang, Huan ;
Lu, Zhongyi ;
Li, Peng ;
Zhang, Qing ;
Jia, Tianye ;
Zhao, Jingya ;
Tian, Shuguang ;
Han, Xuelin ;
Chen, Fangyan ;
Zhang, Changjian ;
Jia, Xiaodong ;
Huang, Liuyu ;
Qu, Fen ;
Han, Li .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2015, 59 (11) :7148-7150
[9]   Multi-azole-resistant Aspergillus fumigatus in the environment in Tanzania [J].
Chowdhary, Anuradha ;
Sharma, Cheshta ;
van den Boom, Mara ;
Yntema, Jan Bart ;
Hagen, Ferry ;
Verweij, Paul E. ;
Meis, Jacques F. .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2014, 69 (11) :2979-2983
[10]   Emergence of Azole-Resistant Aspergillus fumigatus Strains due to Agricultural Azole Use Creates an Increasing Threat to Human Health [J].
Chowdhary, Anuradha ;
Kathuria, Shallu ;
Xu, Jianping ;
Meis, Jacques F. .
PLOS PATHOGENS, 2013, 9 (10)