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Decreased echinocandin susceptibility in Candida parapsilosis causing candidemia and emergence of a pan-echinocandin resistant case in China
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 profi...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9793909/ https://www.ncbi.nlm.nih.gov/pubmed/36440795 http://dx.doi.org/10.1080/22221751.2022.2153086 |
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author | 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 |
author_facet | 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 |
author_sort | Ning, Yating |
collection | PubMed |
description | 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 (MIC(50/90), 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 FKS1(S656P) conferring pan-echinocandin resistance. Our study underscores the necessity of rigorous management of antifungal use and of monitoring for antifungal susceptibility. |
format | Online Article Text |
id | pubmed-9793909 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-97939092022-12-28 Decreased echinocandin susceptibility in Candida parapsilosis causing candidemia and emergence of a pan-echinocandin resistant case in China 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 Emerg Microbes Infect Antimicrobial Agents 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 (MIC(50/90), 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 FKS1(S656P) conferring pan-echinocandin resistance. Our study underscores the necessity of rigorous management of antifungal use and of monitoring for antifungal susceptibility. Taylor & Francis 2022-12-24 /pmc/articles/PMC9793909/ /pubmed/36440795 http://dx.doi.org/10.1080/22221751.2022.2153086 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Antimicrobial Agents 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 Decreased echinocandin susceptibility in Candida parapsilosis causing candidemia and emergence of a pan-echinocandin resistant case in China |
title | Decreased echinocandin susceptibility in Candida parapsilosis causing candidemia and emergence of a pan-echinocandin resistant case in China |
title_full | Decreased echinocandin susceptibility in Candida parapsilosis causing candidemia and emergence of a pan-echinocandin resistant case in China |
title_fullStr | Decreased echinocandin susceptibility in Candida parapsilosis causing candidemia and emergence of a pan-echinocandin resistant case in China |
title_full_unstemmed | Decreased echinocandin susceptibility in Candida parapsilosis causing candidemia and emergence of a pan-echinocandin resistant case in China |
title_short | Decreased echinocandin susceptibility in Candida parapsilosis causing candidemia and emergence of a pan-echinocandin resistant case in China |
title_sort | decreased echinocandin susceptibility in candida parapsilosis causing candidemia and emergence of a pan-echinocandin resistant case in china |
topic | Antimicrobial Agents |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9793909/ https://www.ncbi.nlm.nih.gov/pubmed/36440795 http://dx.doi.org/10.1080/22221751.2022.2153086 |
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