Cong Peishan, Wang Biao, He Hong, Li Xiaoying, Peng Lijing, Liu Ji, Guo Hui, Sun Guirong
Department of Clinical Laboratory, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, Shandong Province, 266000, China.
Department of transfusion medicine, Peking University People's Hospital, Qingdao, China.
BMC Microbiol. 2025 Aug 8;25(1):490. doi: 10.1186/s12866-025-04155-5.
Candidemia caused by Candida glabrata is a serious fungal infection, and rising echinocandin resistance presents a significant clinical challenge. Understanding the drug susceptibility profiles, molecular epidemiology, and mechanisms underlying adaptive echinocandin resistance in C. glabrata is crucial.
A total of 106 C. glabrata strains were isolated from blood cultures of 103 candidemia patients across three medical centers in eastern China. Transcriptome sequencing and whole-genome sequence analysis were used to explore the genomic characteristics of echinocandin-resistant strains. Multi-locus sequence typing (MLST) categorized the isolates into 11 sequence types (STs), with ST7 being the most prevalent (67.9%). Drug susceptibility testing revealed a fluconazole resistance rate of 21.7%, while non-wild-type rates for voriconazole, itraconazole, and posaconazole were 23.6%, 7.5%, and 6.6%, respectively. One isolate (Q2-2) was resistant to all three echinocandins. Two isolates were resistant to micafungin and anidulafungin, respectively. Compared to the echinocandin-sensitive strains, the expression of the Chitin synthetase 3 (CHS3) gene was significantly upregulated in echinocandin-resistant strains. Functional analysis of a CHS3-overexpressing strain (ATCC2001-CHS3-OE), generated through homologous recombination, confirmed echinocandin resistance. Conversely, a CHS3 knockout strain (Q2-2-CHS3Δ) exhibited susceptibility to echinocandins.
Our findings suggest that CHS3 plays a critical compensatory role in echinocandin resistance in C. glabrata, offering a promising target for developing future antifungal strategies.
光滑念珠菌引起的念珠菌血症是一种严重的真菌感染，而棘白菌素耐药性的上升带来了重大的临床挑战。了解光滑念珠菌的药敏谱、分子流行病学以及适应性棘白菌素耐药的潜在机制至关重要。
从中国东部三个医疗中心的103例念珠菌血症患者的血培养物中分离出总共106株光滑念珠菌菌株。采用转录组测序和全基因组序列分析来探索棘白菌素耐药菌株的基因组特征。多位点序列分型（MLST）将分离株分为11种序列类型（STs），其中ST7最为常见（67.9%）。药敏试验显示氟康唑耐药率为21.7%，而伏立康唑、伊曲康唑和泊沙康唑的非野生型率分别为23.6%、7.5%和6.6%。一株分离株（Q2-2）对所有三种棘白菌素均耐药。两株分离株分别对米卡芬净和阿尼芬净耐药。与棘白菌素敏感菌株相比，棘白菌素耐药菌株中几丁质合成酶3（CHS3）基因的表达显著上调。通过同源重组构建产生的CHS3过表达菌株（ATCC2001-CHS3-OE）的功能分析证实了其对棘白菌素的耐药性。相反，CHS3敲除菌株（Q2-2-CHS3Δ）对棘白菌素敏感。
我们的研究结果表明，CHS3在光滑念珠菌对棘白菌素的耐药中起关键的补偿作用，为未来抗真菌策略的开发提供了一个有前景的靶点。
