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SlpA和TcdB中的等位基因连锁差异驱动了不同的免疫和细胞毒性反应,这些反应区分了2型艰难梭菌中的ST01菌株与非ST01菌株。

Allele-linked divergence in SlpA and TcdB drives distinct immune and cytotoxic responses that distinguish ST01 from non-ST01 strains in Clade 2 Clostridioides difficile.

作者信息

Badilla-Lobo Adriana, Quesada-Gómez Carlos, Chaves-Olarte Esteban, Rodríguez César

机构信息

Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.

Programa de Posgrado en Microbiología, Parasitología, Química Clínica e Inmunología, Universidad de Costa Rica, San José, Costa Rica.

出版信息

Access Microbiol. 2025 Sep 10;7(9). doi: 10.1099/acmi.0.000994.v3. eCollection 2025.

DOI:10.1099/acmi.0.000994.v3
PMID:40989932
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12451308/
Abstract

Among the five MLST clades that define the global population structure of the bacterial pathogen , Clade 2 has received special attention due to the global spread, clinical severity and hospital prevalence of ST01 strains. To identify features potentially contributing to the historically attributed higher virulence and epidemic potential of ST01 strains, we compared a range of phenotypic traits across the infection cycle between clinical Clade 2 ST01 and non-ST01 strains from ST41, ST47, ST67, ST154 and ST638. We found no significant differences in canonical virulence-associated characteristics such as spore adherence, motility, biofilm formation and resistance to a disinfectant. However, ST01 strains exhibited distinct profiles in surface layer protein A (SlpA)-mediated immune activation and toxin B (TcdB)-induced cytotoxicity that were consistent with allelic divergence. These findings highlight the need to reconsider current paradigms of Clade 2 hypervirulence and underscore the importance of allele-specific phenotypic variation in developing targeted public health strategies.

摘要

在定义这种细菌病原体全球种群结构的五个多位点序列分型(MLST)分支中,分支2因其ST01菌株的全球传播、临床严重性和医院流行率而受到特别关注。为了确定可能导致ST01菌株在历史上被认为具有更高毒力和流行潜力的特征,我们比较了临床分支2的ST01菌株与来自ST41、ST47、ST67、ST154和ST638的非ST01菌株在感染周期中的一系列表型特征。我们发现,在孢子粘附、运动性、生物膜形成和对消毒剂的抗性等典型毒力相关特征方面没有显著差异。然而,ST01菌株在表层蛋白A(SlpA)介导的免疫激活和毒素B(TcdB)诱导的细胞毒性方面表现出不同的特征,这与等位基因差异一致。这些发现凸显了重新审视当前关于分支2高毒力范式的必要性,并强调了等位基因特异性表型变异在制定针对性公共卫生策略中的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29e5/12451308/4e901b36e21e/acmi-7-00994-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29e5/12451308/e74e207b34a7/acmi-7-00994-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29e5/12451308/4e901b36e21e/acmi-7-00994-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29e5/12451308/e74e207b34a7/acmi-7-00994-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29e5/12451308/4e901b36e21e/acmi-7-00994-g002.jpg

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TFPI is a colonic crypt receptor for TcdB from hypervirulent clade 2 C. difficile.组织因子途径抑制物(TFPI)是来自高毒力2型艰难梭菌的TcdB的结肠隐窝受体。
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