1. Emergence of multiple fluconazole-resistant Candida parapsilosis sensu stricto clones with persistence and transmission in China.
- Author
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Ning, Ya-Ting, Sun, Tian-Shu, Dai, Rong-Chen, Luo, Zheng-Yu, Yu, Shu-Ying, Zhang, Ge, Mei, Ya-Ning, Lin, Yu-Lan, Hasi, Chao-Lu, Chen, Sharon C A, Kong, Fan-Rong, Xiao, Meng, Xu, Ying-Chun, and Zhang, Li
- Subjects
CANDIDA ,CRISPRS ,INTENSIVE care units ,AZOLES ,TRANSCRIPTION factors ,MICROSATELLITE repeats ,ANTIFUNGAL agents - Abstract
Objectives We explored the epidemiological and molecular characteristics of Candida parapsilosis sensu stricto isolates in China, and their mechanisms of azole resistance. Methods Azole susceptibilities of 2318 non-duplicate isolates were determined using CLSI broth microdilution. Isolates were genotyped by a microsatellite typing method. Molecular resistance mechanisms were also studied and functionally validated by CRISPR/Cas9-based genetic alterations. Results Fluconazole resistance occurred in 2.4% (n = 56) of isolates, and these isolates showed a higher frequency of distribution in ICU inpatients compared with susceptible isolates (48.2%, n = 27/56 versus 27.8%, 613/2208; P = 0.019). Microsatellite-genotyping analysis yielded 29 genotypes among 56 fluconazole-resistant isolates, of which 10 genotypes, including 37 isolates, belonged to clusters, persisting and transmitting in Chinese hospitals for 1–29 months. Clusters harbouring Erg11
Y132F (5/10; 50%) were predominant in China. Among these, the second most dominant cluster MT07, including seven isolates, characteristically harbouring Erg11Y132F and Mrr1Q625K , lent its carriage to being one of the strongest associations with cross-resistance and high MICs of fluconazole (>256 mg/L) and voriconazole (2–8 mg/L), causing transmission across two hospitals. Among mutations tested, Mrr1Q625K led to the highest-level increase of fluconazole MIC (32-fold), while mutations located within or near the predicted transcription factor domain of Tac1 (D440Y, T492M and L518F) conferred cross-resistance to azoles. Conclusions This study is the first Chinese report of persistence and transmissions of multiple fluconazole-resistant C. parapsilosis sensu stricto clones harbouring Erg11Y132F , and the first demonstration of the mutations Erg11G307A , Mrr1Q625K , Tac1L263S , Tac1D440Y and Tac1T492M as conferring resistance to azoles. [ABSTRACT FROM AUTHOR]- Published
- 2024
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