Decreased echinocandin susceptibility in Candida parapsilosis causing candidemia and emergence of a pan-echinocandin resistant case in China.
Decreased echinocandin susceptibility in Candida parapsilosis causing candidemia and emergence of a pan-echinocandin resistant case in China.
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DOI：
10.1080/22221751.2022.2153086
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发表时间：
2023-12
影响因子：
13.2
通讯作者：
Zhang, Li
中科院分区：
文献类型：
--
作者：
Ning, Yating;Xiao, Meng;Perlin, David S.;Zhao, Yanan;Lu, Minya;Li, Yi;Luo, Zhengyu;Dai, Rongchen;Li, Shengjie;Xu, Jiajun;Liu, Lingli;He, Hong;Liu, Yun;Li, Fushun;Guo, Yuguang;Chen, Zhongju;Xu, Yingchun;Sun, Tianshu;Zhang, Li
Candida parapsilosis is becoming a predominant non-albicans cause of invasive candidiasis (IC). Echinocandins are the preferred choice for IC treatment and prophylaxis. Resistance to echinocandins in C. parapsilosis has emerged in several countries, but little is known about the susceptibility profile in China or about mechanisms of resistance. Here, we investigated the echinocandin susceptibilities of 2523 C. parapsilosis isolates collected from China and further explored the resistance mechanism among echinocandin-resistant isolates. Anidulafungin exhibited the highest MICs (MIC50/90, 1 and 2 µg/mL; GM, 0.948 µg/mL), while caspofungin showed better activity (0.5 and 1 µg/mL; 0.498 µg/mL). Significantly higher echinocandin MICs were observed among blood-derived isolates compared to others, especially for caspofungin (GM, 1.348 µg/mL vs 0.478 µg/mL). Isolates from ICU and surgical wards also showed higher MICs. Twenty isolates showed intermediate phenotypes for at least one echinocandin. One was resistant to all three echinocandins, fluconazole and voriconazole, which caused breakthrough IC during long-term exposure to micafungin. WGS revealed this isolate carried a mutation S656P in hotspot1 region of Fks1. Bioinformatics analyses suggested that this mutation might lead to an altered protein conformation. CRISPR Cas9-mediated introduction of this mutation into a susceptible reference C. parapsilosis strain increased MICs of all echinocandins 64-fold, with similar results found in the subspecies, C. orthopsilosis and C. metapsilosis. This is the first report of a multi-azole resistant and pan-echinocandin resistant C. parapsilosis isolate, and the identification of a FKS1S656P conferring pan-echinocandin resistance. Our study underscores the necessity of rigorous management of antifungal use and of monitoring for antifungal susceptibility.
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DOI：
10.3390/jof3020024
发表时间：
2017-05-17
期刊：
Journal of fungi (Basel, Switzerland)
影响因子：
--
作者：
da Matta DA;Souza ACR;Colombo AL
通讯作者：
Colombo AL
影响因子：
4.6
作者：
Davari, Amirhossein;Haghani, Iman;Moazeni, Maryam
通讯作者：
Moazeni, Maryam
影响因子：
4.9
作者：
Garcia-Effron, Guillermo;Katiyar, Santosh K.;Perlin, David S.
通讯作者：
Perlin, David S.
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
5.2
作者：
Gomez-Molero, Emilia;Willis, Jesse R.;Bader, Oliver
通讯作者：
Bader, Oliver