Whole genome analysis of echinocandin non-susceptible <i>Candida Glabrata</i> clinical isolates: a multi-center study in China

作者全名："Li, Yi; Hou, Xin; Li, Ruoyu; Liao, Kang; Ma, Ling; Wang, Xiaoming; Ji, Ping; Kong, Haishen; Xia, Yun; Ding, Hui; Kang, Wei; Zhang, Ge; Li, Jin; Xiao, Meng; Li, Yingxing; Xu, Yingchun"

作者地址："[Li, Yi; Kang, Wei; Zhang, Ge; Li, Jin; Xiao, Meng; Xu, Yingchun] Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Clin Lab, State Key Lab Complex Severe & Rare Dis, Beijing, Peoples R China; [Li, Yi; Xiao, Meng; Xu, Yingchun] Beijing Key Lab Mech Res & Precis Diag Invas Funga, Beijing, Peoples R China; [Li, Yi] Chinese Acad Med Sci, Peking Union Med Coll, Grad Sch, Beijing, Peoples R China; [Hou, Xin] Peking Univ Third Hosp, Dept Lab Med, Beijing, Peoples R China; [Li, Ruoyu] Peking Univ First Hosp, Dept Dermatol & Venerol, Beijing, Peoples R China; [Liao, Kang] Sun Yat sen Univ, Affiliated Hosp 1, Dept Lab Med, Guangzhou, Peoples R China; [Ma, Ling] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Wuhan, Peoples R China; [Wang, Xiaoming] First Hosp Jilin Univ, Jilin, Jilin, Peoples R China; [Ji, Ping] Xinjiang Med Univ, Dept Clin Lab, Affiliated Hosp 1, Urumqi, Peoples R China; [Kong, Haishen] Zhejiang Chinese Med Univ, Dept Nephrol, Affiliated Hosp 1, Hangzhou, Peoples R China; [Xia, Yun] Chongqing Med Univ, Affiliated Hosp 1, Chongqing, Peoples R China; [Ding, Hui] Lishui Municipal Cent Hosp, Dept Lab Med, Lishui, Peoples R China; [Li, Yingxing] Peking Union Med Coll Hosp, Natl Infrastruct Translat Med, Biomed Engn Facil, Beijing 100730, Peoples R China"

通信作者："Li, YX (通讯作者)，Peking Union Med Coll Hosp, Natl Infrastruct Translat Med, Biomed Engn Facil, Beijing 100730, Peoples R China."

来源：BMC MICROBIOLOGY

ESI学科分类：MICROBIOLOGY

WOS号：WOS:001106209500001

JCR分区：Q2

影响因子：4

年份：2023

卷号：23

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Candida Glabrata; Echinocandin resistance; Whole genome sequence

摘要："Background Candida glabrata is an important cause of invasive candidiasis. Echinocandins are the first-line treatment of invasive candidiasis caused by C. glabrata. The epidemiological echinocandin sensitivity requires long-term surveillance and the understanding about whole genome characteristics of echinocandin non-susceptible isolates was limited. Results The present study investigated the echinocandin susceptibility of 1650 C. glabrata clinical isolates in China from August 2014 to July 2019. The in vitro activity of micafungin was significantly better than those of caspofungin and anidulafungin (P < 0.001), assessed by MIC50/90 values. Whole genome sequencing was conducted on non-susceptible isolates and geography-matched susceptible isolates. Thirteen isolates (0.79%) were resistant to at least one echinocandin. Six isolates (0.36%) were solely intermediate to caspofungin. Common evolutionary analysis of echinocandin-resistant and echinocandin-intermediate isolates revealed genes related with reduced caspofungin sensitivity, including previously identified sphinganine hydroxylase encoding gene SUR2. Genome-wide association study identified SNPs at subtelometric regions that were associated with echinocandin non-susceptibility. In-host evolution of echinocandin resistance of serial isolates revealed an enrichment for non-synonymous mutations in adhesins genes and loss of subtelometric regions containing adhesin genes. Conclusions The echinocandins are highly active against C. glabrata in China with a resistant rate of 0.79%. Echinocandin non-susceptible isolates carried common evolved genes which are related with reduced caspofungin sensitivity. In-host evolution of C. glabrata accompanied intensive changing of adhesins profile."

基金机构：We are grateful to all participants of the CHIF-NET program.

基金资助正文：We are grateful to all participants of the CHIF-NET program.