Ameline Camille, Seixas Elsa, Barreto Hugo C, Frazão Nelson, Rodrigues Miguel V, Ventura M Rita, Lourenço Marta, Gordo Isabel
GIMM - Gulbenkian Institute for Molecular Medicine, Evolutionary Biology, Lisboa, Portugal.
Université Paris Cité, CNRS, Inserm U1016, Institut Cochin, Paris, France.
PLoS Pathog. 2025 Apr 24;21(4):e1012442. doi: 10.1371/journal.ppat.1012442. eCollection 2025 Apr.
Escherichia coli is a commensal of the intestine of most mammals, but also an important human pathogen. Within a healthy human its population structure is highly dynamic, where typically a dominant E. coli strain is accompanied by several low abundance satellite strains. However, the factors underlying E. coli strain dynamics and evolution within hosts are still poorly understood. Here, we colonised germ-free immune-competent (wild-type) or immune-compromised (Rag2KO) mice, with two phylogenetically distinct strains of E. coli, to determine if strain co-existence and within-strain evolution are shaped by the adaptive immune system. Irrespectively of the immune status of the mice one strain reaches a 100-fold larger abundance than the other. However, the abundance of the dominant strain is significantly higher in Rag2KO mice. Strains co-exist for thousands of generations and accumulate beneficial mutations in genes coding for different resource preferences. A higher rate of mutation accumulation in immune-compromised vs. immune-competent mice is observed and adaptative mutations specific to immune-competent mice are identified. Importantly, the presence of the adaptive immune system selects for mutations that increase stress resistance and the dynamics of such evolutionary events associates with the onset of an antibody response.
大肠杆菌是大多数哺乳动物肠道内的共生菌,但也是一种重要的人类病原体。在健康人体内,其种群结构高度动态变化,通常一种占主导地位的大肠杆菌菌株伴随着几种低丰度的卫星菌株。然而,宿主内大肠杆菌菌株动态变化和进化的潜在因素仍知之甚少。在这里,我们用两种系统发育上不同的大肠杆菌菌株定殖无菌且具有免疫能力(野生型)或免疫受损(Rag2KO)的小鼠,以确定菌株共存和菌株内进化是否受适应性免疫系统影响。无论小鼠的免疫状态如何,一种菌株的丰度比另一种菌株高100倍。然而,Rag2KO小鼠中优势菌株的丰度明显更高。菌株共存数千代,并在编码不同资源偏好的基因中积累有益突变。观察到免疫受损小鼠与免疫能力正常小鼠相比有更高的突变积累率,并鉴定出免疫能力正常小鼠特有的适应性突变。重要的是,适应性免疫系统的存在会选择增加应激抗性的突变,并且这种进化事件的动态变化与抗体反应的开始相关。