Lu Danyi, Feng Lihui
Institute of Pediatrics, Children's Hospital of Fudan University, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Curr Microbiol. 2025 Jul 14;82(9):383. doi: 10.1007/s00284-025-04358-z.
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.
大肠杆菌是婴儿肠道中最早定殖的微生物之一。尽管许多研究聚焦于致病性大肠杆菌菌株的定殖机制，但很少有研究考察共生大肠杆菌在肠道中的适应性基因。在本研究中，我们构建了一株源自人类婴儿的共生大肠杆菌菌株LFYP5的全基因组Tn10突变文库，并检测了其在小鼠肠道中的定殖丰度和适应性基因。我们观察到，LFYP5的大多数转座子突变文库在断奶前大量存续，而在19 - 21日龄左右丰度急剧下降，之后一直维持在低水平。一些突变文库在断奶后可以过度生长几天，但最终也会降至低水平。转座子测序确定参与碳水化合物和氨基酸代谢、氮利用、铁获取及应激反应的基因对小鼠16日龄和18日龄时大肠杆菌在肠道中的定殖至关重要。对特定适应性基因的比较显示，16日龄时更多基因参与代谢（有氧呼吸、呼吸电子传递链、细胞周期和细胞分裂），18日龄时更多基因参与应激反应（DNA修复、对DNA损伤刺激的反应），这表明随着宿主接近断奶年龄，LFYP5从活跃生长状态调整为应激反应状态。本研究系统地考察了共生大肠杆菌在小鼠肠道中的适应性基因，并明确了未来探索潜在分子机制的方向。
