Carbon nutrition of Escherichia coli in the mouse intestine

Abstract

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 nutrientniche 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.

Gene expression analysis of E. coli strains provides insights into the role of gene regulation in diversification

“…Affinities to certain substrates characteristic for the individual habitats such as fucose, a common component of host mucus glycans (Chang et al, 2004), or the plant-derived putrescine (Flores and Galston, 1982) also contributed to ecology-specific gene expression profiles. Furthermore, the high expression of phosphorus uptake systems in environmental strains during starvation might stem from recurrent dual-carbon-/phosphorus-limited conditions specifically in their habitat, which led to an increased co-expression of this system during carbon limitation (Zinn et al, 2004).…”

Control of hexuronate metabolism in Escherichia coli by the two interdependent regulators, ExuR and UxuR: derepression by heterodimer formation

“…Mounting evidence suggests that their catabolism is important for the colonization and motility of Escherichia coli (Chang et al, 2004;Fabich et al, 2008;Peekhaus & Conway, 1998;Sweeney et al, 1996). They are metabolized by the Ashwell pathway, which generates intermediates that are converted to pyruvate via the Entner-Doudoroff pathway.…”

Sialic acid utilization by bacterial pathogens

“…1); however, whereas the neu genes are expressed constitutively the nan genes are induced by Neu5Ac (Vimr et al, 2004), and the hypothesis of tight coupling of Neu5Ac synthesis and activation by NeuB/ NeuA might explain the lack of a futile cycle of Neu5Ac synthesis and degradation, and implies that the catabolic operon is expressed only when exogenous sialic acid is made available (Vimr et al, 2004). Interestingly Chang et al (2004) have shown that the nanAT genes are required for E. coli colonization of the mouse colon, where sialic acidrich mucin appears to be an important nutrient source in vivo. However, studies on the contribution of sialic acid catabolism to virulence using animal models must be interpreted with caution as the distribution and nature of sialic acid may be significantly different in the human host, which affects any possible extrapolation.…”