Clostridioides difficile is the leading cause of healthcare-associated infectious diarrhoea. However, it is increasingly appreciated that healthcare-associated infections derive from both community and healthcare environments, and that the primary sites of C. difficile transmission may be strain-dependent. We conducted a multisite genomic epidemiology study to assess differential genomic evidence of healthcare vs community spread for two of the most common C. difficile strains in the USA: sequence type (ST) 1 (associated with ribotype 027) and ST2 (associated with ribotype 014/020). We performed whole-genome sequencing and phylogenetic analyses on 382 ST1 and ST2 C. difficile isolates recovered from stool specimens collected during standard clinical care at 3 geographically distinct US medical centres between 2010 and 2017. ST1 and ST2 isolates both displayed some evidence of phylogenetic clustering by study site, but clustering was stronger and more apparent in ST1, consistent with our healthcare-based study more comprehensively sampling local transmission of ST1 compared to ST2 strains. Analyses of pairwise single-nucleotide variant (SNV) distance distributions were also consistent with more evidence of healthcare transmission of ST1 compared to ST2, with 44 % of ST1 isolates being within two SNVs of another isolate from the same geographical collection site compared to 5.5 % of ST2 isolates (P-value=<0.001). Conversely, ST2 isolates were more likely to have close genetic neighbours across disparate geographical sites compared to ST1 isolates, further supporting non-healthcare routes of spread for ST2 and highlighting the potential for misattributing genomic similarity among ST2 isolates to recent healthcare transmission. Finally, we estimated a lower evolutionary rate for the ST2 lineage compared to the ST1 lineage using Bayesian timed phylogenomic analyses, and hypothesize that this may contribute to observed differences in geographical concordance among closely related isolates. Together, these findings suggest that ST1 and ST2, while both common causes of C. difficile infection in hospitals, show differential reliance on community and hospital spread. This conclusion supports the need for strain-specific criteria for interpreting genomic linkages and emphasizes the importance of considering differences in the epidemiology of circulating strains when devising interventions to reduce the burden of C. difficile infections.

中文翻译：

---

美国对艰难梭菌感染的多站点基因组流行病学研究支持两种常见菌株的医疗保健与社区传播的不同作用

艰难梭菌 是医疗保健相关感染性腹泻的主要原因。然而，人们越来越认识到与医疗保健相关的感染来自社区和医疗保健环境，并且艰难梭菌传播的主要部位可能是菌株依赖性的。我们进行了一项多站点基因组流行病学研究，以评估美国两种最常见的艰难梭菌菌株的医疗保健与社区传播的差异基因组证据：序列类型 (ST) 1（与核糖型 027 相关）和 ST2（与核糖型 014 相关） /020)。我们对 382 个 ST1 和 ST2艰难梭菌进行了全基因组测序和系统发育分析 从 2010 年至 2017 年间在 3 个地理位置不同的美国医疗中心的标准临床护理期间收集的粪便标本中回收的分离株。ST1 和 ST2 分离株均显示出研究地点的系统发育聚类的一些证据，但在 ST1 中聚类更强且更明显，与我们的一致与 ST2 菌株相比，基于医疗保健的研究更全面地采样了 ST1 的本地传播。与 ST2 相比，成对单核苷酸变异 (SNV) 距离分布的分析也与 ST1 的医疗保健传播的更多证据一致，44% 的 ST1 分离株位于来自同一地理采集地点的另一个分离株的两个 SNV 内，而这一比例为 5.5% ST2 分离株 ( P-值=<0.001)。相反，与 ST1 分离株相比，ST2 分离株更有可能在不同的地理位置具有密切的遗传邻居，这进一步支持了 ST2 的非医疗传播途径，并突出了将 ST2 分离株之间的基因组相似性误认为是最近的医疗保健传播的可能性。最后，我们使用贝叶斯定时系统发育分析估计了 ​​ST2 谱系与 ST1 谱系相比较低的进化率，并假设这可能有助于观察到密切相关的分离株之间地理一致性的差异。总之，这些发现表明 ST1 和 ST2 是艰难梭菌的常见原因 医院感染，表现出对社区和医院传播的不同依赖。这一结论支持了解释基因组联系的菌株特异性标准的必要性，并强调了在设计干预措施以减轻艰难梭菌感染负担时考虑循环菌株流行病学差异的重要性。