Beebe Merilyn A, Paredes-Sabja Daniel, Kociolek Larry K, Rodríguez César, Sorg Joseph A
Department of Biology, Texas A&M University, College Station, TX 77845.
Division of Pediatric Infectious Diseases, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611.
bioRxiv. 2025 Jan 10:2025.01.10.632434. doi: 10.1101/2025.01.10.632434.
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 has 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 ribotypes (., RT027), recent years have seen several other ribotypes dominate the clinical landscape (, RT106 and RT078). Some ribotypes are associated with severe disease and / or increased recurrence rates, but why are certain ribotypes 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 core biological processes of are conserved across ribotypes / clades. We tested this hypothesis by observing the growth kinetics, sporulation, germination, bile acid sensitivity, bile salt hydrolase activity, and surface motility of fifteen 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.
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 the 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.
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，通常按核糖体分型进行。虽然目前的许多文献都集中在一两种突出的核糖体分型（如RT027）上，但近年来其他几种核糖体分型在临床中占据了主导地位（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具危害性仍然未知。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基因多样性的结果。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个菌株的生长动力学、孢子形成、萌发、胆汁酸敏感性、胆盐水解酶活性和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、孢子形成和对胆盐毒性的抗性）在进化枝/核糖体分型之间非常一致。这表明在临床环境中观察到的差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。
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/核糖体分型中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/复发的差异无关，是开发用于治疗艰难梭菌相关感染的疗法的理想靶点。
