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Structural and mechanistic insights into fungal β-1,3-glucan synthase FKS1.真菌β-1,3-葡聚糖合成酶 FKS1 的结构和机制见解。
Nature. 2023 Apr;616(7955):190-198. doi: 10.1038/s41586-023-05856-5. Epub 2023 Mar 22.
2
Echinocandin Resistance in Candida auris Occurs in the Murine Gastrointestinal Tract Due to Mutations.棘白菌素耐药的耳念珠菌在鼠类胃肠道中出现是由于突变。
Antimicrob Agents Chemother. 2023 Apr 18;67(4):e0124322. doi: 10.1128/aac.01243-22. Epub 2023 Mar 15.
3
Update on the Pathogenesis, Virulence, and Treatment of .关于……的发病机制、毒力及治疗的最新进展 (原文不完整,此为根据现有内容尽量完整的翻译)
Pathog Immun. 2022 Oct 21;7(2):46-65. doi: 10.20411/pai.v7i2.535. eCollection 2022.
4
Pan-resistant Candida auris: New York subcluster susceptible to antifungal combinations.全耐药耳念珠菌:对抗真菌联合疗法敏感的纽约亚群
Lancet Microbe. 2020 Sep;1(5):e193-e194. doi: 10.1016/S2666-5247(20)30090-2. Epub 2020 Aug 3.
5
ΔF659 and F659S substitutions at the HS1 of FKS2 gene, along with E655A and W715L upstream and downstream substitutions, correlate with high ibrexafungerp MICs against Candidaglabrata.FKS2 基因 HS1 处的 ΔF659 和 F659S 取代,以及上下游的 E655A 和 W715L 取代,与对 Candida glabrata 的高伊曲康唑 MIC 值相关。
Clin Microbiol Infect. 2022 Aug;28(8):1154.e5-1154.e8. doi: 10.1016/j.cmi.2022.04.003. Epub 2022 Apr 12.
6
Fatal Breakthrough Candidemia in an Immunocompromised Patient in Kuwait Due to Exhibiting Reduced Susceptibility to Echinocandins and Carrying a Novel Mutation in Hotspot-1 of .科威特一名免疫功能低下患者发生致命性突破性念珠菌血症,原因是对棘白菌素敏感性降低且在……的热点1携带一种新突变。
J Fungi (Basel). 2022 Mar 6;8(3):267. doi: 10.3390/jof8030267.
7
Molecular characterisation of Candida auris isolates from immunocompromised patients in a tertiary-care hospital in Kuwait reveals a novel mutation in FKS1 conferring reduced susceptibility to echinocandins.来自科威特一家三级保健医院免疫功能低下患者的耳念珠菌分离株的分子特征显示 FKS1 中的一种新突变导致对棘白菌素类药物的敏感性降低。
Mycoses. 2022 Mar;65(3):331-343. doi: 10.1111/myc.13419. Epub 2022 Jan 3.
8
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Antimicrob Agents Chemother. 2022 Jan 18;66(1):e0165221. doi: 10.1128/AAC.01652-21. Epub 2021 Nov 15.
9
Genome-Wide Analysis of Experimentally Evolved Candida auris Reveals Multiple Novel Mechanisms of Multidrug Resistance.全基因组分析实验进化的假丝酵母菌揭示了多种新型多药耐药机制。
mBio. 2021 Apr 5;12(2):e03333-20. doi: 10.1128/mBio.03333-20.
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Molecular Epidemiology of Outbreak in a Major Secondary-Care Hospital in Kuwait.科威特一家大型二级护理医院疫情的分子流行病学
J Fungi (Basel). 2020 Nov 21;6(4):307. doi: 10.3390/jof6040307.

新型非热点 Fks1 突变导致耳念珠菌对棘白菌素类药物的耐药性。

Novel Non-Hot Spot Modification in Fks1 of Candida auris Confers Echinocandin Resistance.

机构信息

Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA.

Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, Brazil.

出版信息

Antimicrob Agents Chemother. 2023 Jun 15;67(6):e0042323. doi: 10.1128/aac.00423-23. Epub 2023 May 24.

DOI:10.1128/aac.00423-23
PMID:37222585
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10269051/
Abstract

We determined the echinocandin susceptibility and genotypes of 13 clinical isolates of Candida auris that were recovered from 4 patients at a tertiary care center in Salvador, Brazil. Three isolates were categorized as echinocandin-resistant, and they harbored a novel mutation that led to an amino acid change W691L located downstream from hot spot 1. When introduced to echinocandin-susceptible C. auris strains by CRISPR/Cas9, Fks1 W691L induced elevated MIC values to all echinocandins (anidulafungin, 16 to 32×; caspofungin, >64×; micafungin, >64×).

摘要

我们从巴西萨尔瓦多一家三级保健中心的 4 名患者身上分离出 13 株临床分离的耳念珠菌,确定了它们对棘白菌素的敏感性和基因型。3 株被归类为棘白菌素耐药,它们携带一种新的突变,导致位于热点 1 下游的氨基酸改变 W691L。当通过 CRISPR/Cas9 引入到对棘白菌素敏感的耳念珠菌菌株中时,Fks1 W691L 导致所有棘白菌素(安尼卡fungin,16 至 32×;卡泊芬净,>64×;米卡芬净,>64×)的 MIC 值升高。