Midani Firas S, Danhof Heather A, Mathew Nathanael, Ardis Colleen K, Garey Kevin W, Spinler Jennifer K, Britton Robert A
Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas, USA.
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
bioRxiv. 2024 Aug 15:2024.08.15.608124. doi: 10.1101/2024.08.15.608124.
is a gram-positive spore-forming pathogen that commonly causes diarrheal infections in the developed world. Although is a genetically diverse species, certain ribotypes are overrepresented in human infections. It is unknown if metabolic adaptations are essential for the emergence of these epidemic ribotypes. Here, we tested carbon substrate utilization by 88 isolates and looked for differences in growth between 22 ribotypes. By profiling clinical isolates, we assert that is a generalist species capable of growing on a variety of carbon substrates. Further, strains clustered by phylogenetic relationship and displayed ribotype-specific and clade-specific metabolic capabilities. Surprisingly, we observed that two emerging lineages, ribotypes 023 and 255, have divergent metabolic phenotypes. In addition, although Clade 5 is the most evolutionary distant clade and often detected in animals, it displayed more robust growth on simple dietary sugars than Clades 1-4. Altogether, our results corroborate the generalist metabolic strategy of and demonstrate lineage-specific metabolic capabilities. In addition, our approach can be adapted to the study of additional pathogens to ascertain their metabolic niches in the gut.
The gut pathogen utilizes a wide range of carbon sources. Microbial communities can be rationally designed to combat by depleting its preferred nutrients in the gut. However, is genetically diverse with hundreds of identified ribotypes and most of its metabolic studies were performed with lab-adapted strains. Here, we profiled carbon metabolism by a myriad of clinical isolates. While the metabolic capabilities of these isolates clustered by their genetic lineage, we observed surprising metabolic divergence between two emerging lineages. We also found that the most genetically distant clade grew robustly on simple dietary sugars, posing intriguing questions about the adaptation of to the human gut. Altogether, our results underscore the importance of considering the metabolic diversity of pathogens in the study of their evolution and the rational design of therapeutic interventions.
是一种革兰氏阳性产芽孢病原体，在发达国家通常引起腹泻感染。虽然是一个基因多样的物种，但某些核糖型在人类感染中占比过高。尚不清楚代谢适应性对于这些流行核糖型的出现是否至关重要。在此，我们测试了88株分离株对碳底物的利用情况，并寻找22种核糖型之间生长的差异。通过对临床分离株进行分析，我们断言是一种能够在多种碳底物上生长的泛养型物种。此外，菌株按系统发育关系聚类，并表现出核糖型特异性和进化枝特异性的代谢能力。令人惊讶的是，我们观察到两个新兴谱系，核糖型023和255，具有不同的代谢表型。此外，虽然进化枝5是进化距离最远的进化枝，且常在动物中检测到，但它在简单膳食糖上的生长比进化枝1 - 4更强劲。总之，我们的结果证实了的泛养型代谢策略，并证明了谱系特异性的代谢能力。此外，我们的方法可适用于研究其他病原体，以确定它们在肠道中的代谢生态位。
肠道病原体利用多种碳源。可以合理设计微生物群落，通过耗尽其在肠道中的首选营养物质来对抗。然而，基因多样，有数百种已鉴定的核糖型，并且其大多数代谢研究是用实验室适应菌株进行的。在此，我们通过大量临床分离株分析了碳代谢。虽然这些分离株的代谢能力按其遗传谱系聚类，但我们观察到两个新兴谱系之间存在惊人的代谢差异。我们还发现，遗传距离最远的进化枝在简单膳食糖上生长强劲，这对适应人类肠道提出了有趣的问题。总之，我们的结果强调了在研究病原体进化和合理设计治疗干预措施时考虑病原体代谢多样性的重要性。
