Whole genome analysis of echinocandin non-susceptible Candida Glabrata clinical isolates: a multi-center study in China.
Whole genome analysis of echinocandin non-susceptible Candida Glabrata clinical isolates: a multi-center study in China.
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DOI：
10.1186/s12866-023-03105-3
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发表时间：
2023-11-16
期刊：
影响因子：
4.2
通讯作者：
Xu, Yingchun
中科院分区：
文献类型：
--
作者：
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
光滑念珠菌是侵袭性念珠菌病的重要病因。棘白菌素是治疗由念珠菌引起的侵袭性念珠菌病的一线药物。光滑的棘白菌素敏感性的流行需要长期监测，而对棘白菌素非敏感株的全基因组特征的了解有限。本文研究了1650 C. 2014年8月至2019年7月在中国发现的光滑念珠菌临床分离株。MIC 50/90值显示米卡芬净的体外抗菌活性明显优于卡泊芬净和阿尼芬净（P < 0.001）。对非敏感分离株和地理匹配的敏感分离株进行全基因组测序。13株（0.79%）对至少一种棘白菌素耐药。6株分离株（0.36%）仅为卡泊芬净中间产物。棘白菌素耐药和棘白菌素中间分离株的常见进化分析揭示了与卡泊芬净敏感性降低相关的基因，包括先前鉴定的鞘氨醇羟化酶编码基因SUR 2。全基因组关联研究确定了与棘白菌素非敏感性相关的亚端粒区域的SNP。棘白菌素抗性的系列分离株的宿主内进化揭示了粘附素基因的非同义突变的富集和含有粘附素基因的亚端粒区域的丢失。棘白菌素对C.光滑型，耐药率为0.79%。棘白菌素非敏感分离株携带与卡泊芬净敏感性降低相关的共同进化基因。C.光滑的同时伴随着粘附素谱的强烈变化。在线版本包含补充材料，可通过10.1186/s12866-023-03105-3获得。
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. 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. 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. The online version contains supplementary material available at 10.1186/s12866-023-03105-3.
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DOI：
10.1016/j.cub.2017.11.027
发表时间：
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期刊：
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影响因子：
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