美国费城儿童医院Joseph P. Zackular研究小组发现，肠球菌增强艰难梭菌的致病。2022年11月16日，《自然》杂志在线发表了这项成果。

研究人员表明，肠道中一组耐抗生素的机会型病原体（肠球菌）的扩张增强了艰难梭菌的生存能力和疾病发生。通过营养限制和交叉喂养的平行过程，肠球菌塑造了肠道内的代谢环境，并重新规划了艰难梭菌的代谢过程。肠球菌提供了可发酵的氨基酸，包括亮氨酸和鸟氨酸，从而提高艰难梭菌在抗生素干扰的肠道中的适应性。肠球菌通过精氨酸分解平行消耗精氨酸，为艰难梭菌提供了代谢线索，促进了毒力的增加。

研究人员发现，在多种小鼠感染模型和艰难梭菌感染的患者中，这两种致病性生物体之间存在微生物相互作用的证据。这些发现为病原微生物群在艰难梭菌感染的易感性和严重性方面的作用提供了机制上的见解。

据了解，肠道病原体在胃肠道中暴露于动态的多微生物环境中。这种微生物群落已被证明在感染期间很重要，但很少有例子说明微生物的相互作用如何影响入侵病原体的毒性。

附：英文原文

Title: Enterococci enhance Clostridioides difficile pathogenesis

Author: Smith, Alexander B., Jenior, Matthew L., Keenan, Orlaith, Hart, Jessica L., Specker, Jonathan, Abbas, Arwa, Rangel, Paula C., Di, Chao, Green, Jamal, Bustin, Katelyn A., Gaddy, Jennifer A., Nicholson, Maribeth R., Laut, Clare, Kelly, Brendan J., Matthews, Megan L., Evans, Daniel R., Van Tyne, Daria, Furth, Emma E., Papin, Jason A., Bushman, Frederic D., Erlichman, Jessi, Baldassano, Robert N., Silverman, Michael A., Dunny, Gary M., Prentice, Boone M., Skaar, Eric P., Zackular, Joseph P.

Issue&Volume: 2022-11-16

Abstract: Enteric pathogens are exposed to a dynamic polymicrobial environment in the gastrointestinal tract1. This microbial community has been shown to be important during infection, but there are few examples illustrating how microbial interactions can influence the virulence of invading pathogens2. Here we show that expansion of a group of antibiotic-resistant, opportunistic pathogens in the gut—the enterococci—enhances the fitness and pathogenesis of Clostridioides difficile. Through a parallel process of nutrient restriction and cross-feeding, enterococci shape the metabolic environment in the gut and reprogramme C. difficile metabolism. Enterococci provide fermentable amino acids, including leucine and ornithine, which increase C. difficile fitness in the antibiotic-perturbed gut. Parallel depletion of arginine by enterococci through arginine catabolism provides a metabolic cue for C. difficile that facilitates increased virulence. We find evidence of microbial interaction between these two pathogenic organisms in multiple mouse models of infection and patients infected with C. difficile. These findings provide mechanistic insights into the role of pathogenic microbiota in the susceptibility to and the severity of C. difficile infection.

DOI: 10.1038/s41586-022-05438-x

Source: https://www.nature.com/articles/s41586-022-05438-x