Novel FKS1 and FKS2 modifications in a high-level echinocandin resistant clinical isolate of Candida glabrata
| Autor: | Xin Hou, Kelley R. Healey, Erika Shor, Milena Kordalewska, Cristina Jiménez Ortigosa, Padmaja Paderu, Meng Xiao, He Wang, Ying Zhao, Li-Yan Lin, Yan-Hai Zhang, Yong-Zhe Li, Ying-Chun Xu, David S. Perlin, Yanan Zhao |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Emerging Microbes and Infections, Vol 8, Iss 1, Pp 1619-1625 (2019) |
| Druh dokumentu: | article |
| ISSN: | 22221751 2222-1751 |
| DOI: | 10.1080/22221751.2019.1684209 |
| Popis: | ABSTRACTEchinocandin resistance in Candida glabrata poses a serious clinical challenge. The underlying resistance mechanism of a pan-echinocandin-resistant C. glabrata isolate (strain L74) was investigated in this study. FKS mutants carrying specific mutations found in L74 were reconstructed by the Alt-R CRISPR-Cas9 system (Fks1 WT/Fks2-E655K, strain CRISPR 31) and site-directed mutagenesis (strain fks1Δ/Fks2-E655K). Sequence analysis of strain L74 revealed a premature stop codon W508stop in FKS1 and an E655K mutation preceding the hotspot 1 region in FKS2. Introduction of the Fks2-E655K mutation in ATCC 2001 (strain CRISPR 31) conferred a modest reduction in susceptibility. However, the same FKS2 mutation in the fks1Δ background (strain fks1Δ/Fks2-E655K) resulted in high levels of resistance to echinocandins. Glucan synthase isolated from L74 was dramatically less sensitive to micafungin (MCF) relative to ATCC 2001. Both FKS1/FKS2 transcript ratios and Fks1/Fks2 protein ratios were significantly lower in L74 and fks1Δ/Fks2-E655K compared to ATCC 2001 and CRISPR 31 (P |
| Databáze: | Directory of Open Access Journals |
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