Department of Laboratory Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, China.
BMC Microbiol. 2023 Nov 16;23(1):341. doi: 10.1186/s12866-023-03105-3.
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 MIC 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.
光滑念珠菌是侵袭性念珠菌病的重要病因。棘白菌素类是治疗由光滑念珠菌引起的侵袭性念珠菌病的一线药物。棘白菌素敏感性的流行病学需要长期监测，并且对棘白菌素不敏感分离株的全基因组特征的了解有限。
本研究调查了 2014 年 8 月至 2019 年 7 月中国 1650 株光滑念珠菌临床分离株的棘白菌素敏感性。通过 MIC 值评估，米卡芬净的体外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。有 13 株（0.79%）对至少一种棘白菌素耐药。6 株（0.36%）仅对卡泊芬净中介。棘白菌素耐药和棘白菌素中介分离株的共同进化分析显示，与卡泊芬净敏感性降低相关的基因，包括先前鉴定的神经鞘氨醇羟化酶编码基因 SUR2。全基因组关联研究确定了与棘白菌素不敏感相关的亚端粒区域的 SNPs。连续分离株棘白菌素耐药的体内进化显示，在黏附素基因中存在非同义突变的富集，并且含有黏附素基因的亚端粒区域丢失。
棘白菌素类在中国对光滑念珠菌具有高度活性，耐药率为 0.79%。棘白菌素不敏感分离株携带常见的进化基因，这些基因与卡泊芬净敏感性降低有关。光滑念珠菌的体内进化伴随着黏附素谱的密集变化。
