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对各种核糖体分型的表型分析揭示了核心过程之间的一致性。

Phenotypic analysis of various ribotypes reveals consistency among core processes.

作者信息

Beebe Merilyn A, Paredes-Sabja Daniel, Kociolek Larry K, Rodríguez César, Sorg Joseph A

机构信息

Department of Biology, Texas A&M University, College Station, Texas, USA.

Division of Pediatric Infectious Diseases, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.

出版信息

Appl Environ Microbiol. 2025 Jun 24:e0096425. doi: 10.1128/aem.00964-25.

Abstract

infections (CDI) cause almost 300,000 hospitalizations per year, of which ~15%-30% are the result of recurring infections. The prevalence and persistence of CDI in hospital settings have resulted in an extensive collection of clinical isolates and their classification, typically by ribotype. While much of the current literature focuses on one or two prominent epidemic ribotypes (e.g., RT027), recent years have seen several other ribotypes dominate the clinical landscape (e.g., RT106 and RT078). Some ribotypes are associated with severe disease and/or increased recurrence rates, but why certain ribotypes are more prominent or harmful than others remains unknown. Because has a large, open pan-genome, this observed relationship between ribotype and clinical outcome could be a result of the genetic diversity of . Thus, we hypothesize that the core biological processes of are conserved across ribotypes/clades. We tested this hypothesis by observing the growth kinetics, sporulation, germination, production of toxin A and toxin B, bile acid sensitivity, bile salt hydrolase activity, and surface motility of 15 strains belonging to various ribotypes spanning each known clade. In viewing these phenotypes across each strain, we see that core phenotypes (growth, germination, sporulation, and resistance to bile salt toxicity) are remarkably consistent across clades/ribotypes. This suggests that variations observed in the clinical setting may be due to unidentified factors in the accessory genome or due to unknown host factors.IMPORTANCE infections impact thousands of individuals every year, many of whom experience recurring infections. Clinical studies have reported an unexplained correlation between some clades/ribotypes of and disease severity/recurrence. Here, we demonstrate that strains across major clades/ribotypes are consistent in their core phenotypes. This suggests that such phenotypes are not responsible for variations in disease severity/recurrence and are ideal targets for the development of therapeutics meant to treat -related infections.

摘要

艰难梭菌感染(CDI)每年导致近30万例住院治疗,其中约15%-30%是反复感染的结果。CDI在医院环境中的流行和持续存在导致了大量临床分离株的收集及其分类,通常是通过核糖体分型。虽然目前的许多文献都集中在一两种突出的流行核糖体分型(如RT027)上,但近年来其他几种核糖体分型也主导了临床格局(如RT106和RT078)。一些核糖体分型与严重疾病和/或复发率增加有关,但为什么某些核糖体分型比其他分型更突出或更有害仍然未知。由于艰难梭菌具有庞大的开放泛基因组,这种观察到的核糖体分型与临床结果之间的关系可能是艰难梭菌遗传多样性的结果。因此,我们假设艰难梭菌的核心生物学过程在核糖体分型/进化枝中是保守的。我们通过观察属于跨越每个已知艰难梭菌进化枝的各种核糖体分型的15株菌株的生长动力学、孢子形成、萌发、毒素A和毒素B的产生、胆汁酸敏感性、胆汁盐水解酶活性以及表面运动性来检验这一假设。在观察每个菌株的这些表型时,我们发现核心表型(生长、萌发、孢子形成以及对胆汁盐毒性的抗性)在进化枝/核糖体分型中非常一致。这表明在临床环境中观察到的变异可能是由于辅助基因组中未识别的因素或未知的宿主因素。重要性艰难梭菌感染每年影响数千人,其中许多人经历反复感染。临床研究报告了艰难梭菌的一些进化枝/核糖体分型与疾病严重程度/复发之间存在无法解释的相关性。在这里,我们证明主要进化枝/核糖体分型的艰难梭菌菌株在其核心表型上是一致的。这表明这些表型与疾病严重程度/复发的变异无关,并且是开发用于治疗艰难梭菌相关感染的疗法的理想靶点。

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