Fitness gene Characterization of Human Infant-Derived Commensal Escherichia coli LFYP5 in the Murine Gut.

Escherichia coli is one of the earliest colonizers in the infant gut. Despite many studies focused on the colonization mechanisms of pathogenic E. coli strains, few have examined the fitness genes of commensal E. coli in the gut. In this study, we constructed a genome-wide Tn10-mutant library of a human infant-derived commensal E. coli strain LFYP5 and examined its colonization abundance and fitness genes in the mouse gut. We observed that the majority of the transposon mutant libraries of LFYP5 persisted abundantly before weaning, and the abundance decreased precipitously around 19-21 days of age and remained low afterwards. Some mutant libraries could overgrow for several days after weaning, but also decreased to a low level eventually. Transposon sequencing identified genes participating in carbohydrate and amino acid metabolism, nitrogen utilization, iron acquisition, and stress response as essential for E. coli colonization in the gut at both day 16 and day 18 of mouse age. Comparison of the specific fitness genes revealed more genes involved in metabolism (aerobic respiration, respiratory electron transport chain, cell cycle and cell division) for day 16 and more genes involved in stress response (DNA repair, response to DNA damage stimulus) for day 18, suggesting that LFYP5 adjusted from active growth to stress response as the host approached the weaning age. This study systematically examined the fitness genes of commensal E. coli in the murine gut and pinpointed future directions to explore the underlying molecular mechanisms.