Infection leaves a genetic and functional mark on the gut population of a commensal bacterium

Gastrointestinal infection changes microbiome composition and gene expression. In this study, we demonstrate that enteric infection also promotes rapid genetic adaptation in a gut commensal. Measurements of Bacteroides thetaiotaomicron population dynamics within gnotobiotic mice reveal that these populations are relatively stable in the absence of infection; introduction of the enteropathogen Citrobacter rodentium reproducibly promotes rapid selection for a single-nucleotide variant with increased fitness. This mutation promotes resistance to oxidative stress by altering the sequence of a protein, IctA, that is essential for fitness during infection. We identified commensals from multiple phyla that attenuate the selection of this variant during infection. These species increase the levels of vitamin B6 in the gut lumen; direct administration of this vitamin is sufficient to significantly reduce variant expansion in infected mice. Our work demonstrates that a self-limited enteric infection can leave a stable mark on resident commensal populations that increases fitness during infection. The deposited data consists of whole genome sequencing data of barcoded Bacteroides thetaiotaomicron strains isolated from mouse gut with or without Citrobacter rodentium infection and ancestral naive strains that have not been in mice.胃肠道感染可改变微生物组组成与基因表达。本研究证实，肠道感染还可促进肠道共生菌发生快速遗传适应。对悉生小鼠（gnotobiotic mice）体内多形拟杆菌(Bacteroides thetaiotaomicron)种群动态的检测结果显示，未发生感染时该种群相对稳定；引入肠道致病菌鼠柠檬酸杆菌(Citrobacter rodentium)后，可重复性地促使快速筛选出适合度提升的单核苷酸变异（single-nucleotide variant）株。该突变通过改变蛋白质IctA的序列提升菌株的氧化应激抗性，而IctA是感染期间维持菌株适合度所必需的蛋白。我们从多个菌门中鉴定出可在感染期间减弱该变异株被筛选的共生菌，这些共生菌可提升肠腔内的维生素B6水平；直接补充该维生素即可显著降低感染小鼠体内的变异株扩增程度。本研究表明，自限性肠道感染可在常驻共生菌群中留下持久印记，从而提升感染期间菌株的适合度。 本次上传的数据集包含从感染或未感染鼠柠檬酸杆菌的小鼠肠道中分离的带条形码多形拟杆菌(Bacteroides thetaiotaomicron)菌株，以及未在小鼠肠道内定植过的原始野生菌株的全基因组测序数据。