Chang Dong-Eun, Smalley Darren J, Tucker Don L, Leatham Mary P, Norris Wendy E, Stevenson Sarah J, Anderson April B, Grissom Joe E, Laux David C, Cohen Paul S, Conway Tyrrell
Advanced Center for Genome Technology, Department of Botany and Microbiology, University of Oklahoma, Norman, OK 73019-0245, USA.
Proc Natl Acad Sci U S A. 2004 May 11;101(19):7427-32. doi: 10.1073/pnas.0307888101. Epub 2004 May 3.
Whole-genome expression profiling revealed Escherichia coli MG1655 genes induced by growth on mucus, conditions designed to mimic nutrient availability in the mammalian intestine. Most were nutritional genes corresponding to catabolic pathways for nutrients found in mucus. We knocked out several pathways and tested the relative fitness of the mutants for colonization of the mouse intestine in competition with their wild-type parent. We found that only mutations in sugar pathways affected colonization, not phospholipid and amino acid catabolism, not gluconeogenesis, not the tricarboxylic acid cycle, and not the pentose phosphate pathway. Gluconate appeared to be a major carbon source used by E. coli MG1655 to colonize, having an impact on both the initiation and maintenance stages. N-acetylglucosamine and N-acetylneuraminic acid appeared to be involved in initiation, but not maintenance. Glucuronate, mannose, fucose, and ribose appeared to be involved in maintenance, but not initiation. The in vitro order of preference for these seven sugars paralleled the relative impact of the corresponding metabolic lesions on colonization: gluconate > N-acetylglucosamine > N-acetylneuraminic acid = glucuronate > mannose > fucose > ribose. The results of this systematic analysis of nutrients used by E. coli MG1655 to colonize the mouse intestine are intriguing in light of the nutrient-niche hypothesis, which states that the ecological niches within the intestine are defined by nutrient availability. Because humans are presumably colonized with different commensal strains, differences in nutrient availability may provide an open niche for infecting E. coli pathogens in some individuals and a barrier to infection in others.
全基因组表达谱分析揭示了大肠杆菌MG1655在黏液上生长时被诱导表达的基因，这些条件旨在模拟哺乳动物肠道中的营养可利用性。大多数是与黏液中发现的营养物质分解代谢途径相对应的营养基因。我们敲除了几条途径，并测试了突变体与野生型亲本竞争在小鼠肠道定殖时的相对适应性。我们发现只有糖代谢途径的突变影响定殖，而磷脂和氨基酸分解代谢、糖异生、三羧酸循环以及磷酸戊糖途径的突变则不影响。葡萄糖酸盐似乎是大肠杆菌MG1655定殖所利用的主要碳源，对起始和维持阶段均有影响。N-乙酰葡糖胺和N-乙酰神经氨酸似乎参与起始阶段，但不参与维持阶段。葡糖醛酸、甘露糖、岩藻糖和核糖似乎参与维持阶段，但不参与起始阶段。这七种糖在体外的偏好顺序与相应代谢损伤对定殖的相对影响平行：葡萄糖酸盐＞N-乙酰葡糖胺＞N-乙酰神经氨酸 = 葡糖醛酸＞甘露糖＞岩藻糖＞核糖。鉴于营养生态位假说，即肠道内的生态位由营养可利用性定义，对大肠杆菌MG1655定殖小鼠肠道所利用营养物质的这一系统分析结果很有趣。因为人类可能被不同的共生菌株定殖，营养可利用性的差异可能为某些个体中感染性大肠杆菌病原体提供一个开放的生态位，而对另一些个体则构成感染屏障。
