Mammals are aerobes that harbor an intestinal ecosystem dominated by large numbers of anaerobic microorganisms. However, the role of oxygen in the intestinal ecosystem is largely unexplored. We used systematic mutational analysis to determine the role of respiratory metabolism in the streptomycin-treated mouse model of intestinal colonization. Here we provide evidence that aerobic respiration is required for commensal and pathogenic Escherichia coli to colonize mice. Our results showed that mutants lacking ATP synthase, which is required for all respiratory energy-conserving metabolism, were eliminated by competition with respiratory-competent wild-type strains. Mutants lacking the high-affinity cytochrome bd oxidase, which is used when oxygen tensions are low, also failed to colonize. However, the low-affinity cytochrome bo 3 oxidase, which is used when oxygen tension is high, was found not to be necessary for colonization. Mutants lacking either nitrate reductase or fumarate reductase also had major colonization defects. The results showed that the entire E. coli population was dependent on both microaerobic and anaerobic respiration, consistent with the hypothesis that the E. coli niche is alternately microaerobic and anaerobic, rather than static. The results indicate that success of the facultative anaerobes in the intestine depends on their respiratory flexibility. Despite competition for relatively scarce carbon sources, the energy efficiency provided by respiration may contribute to the widespread distribution (i.e., success) of E. coli strains as commensal inhabitants of the mammalian intestine.

No abstract

Mutant screens and transcriptome studies led us to consider whether the metabolism of glucose polymers, i.e., maltose, maltodextrin, and glycogen, is important for Escherichia coli colonization of the intestine. By using the streptomycin-treated mouse model, we found that catabolism of the disaccharide maltose provides a competitive advantage in vivo to pathogenic E. coli O157:H7 and commensal E. coli K-12, whereas degradation of exogenous forms of the more complex glucose polymer, maltodextrin, does not. The endogenous glucose polymer, glycogen, appears to play an important role in colonization, since mutants that are unable to synthesize or degrade glycogen have significant colonization defects. In support of the hypothesis that E. coli relies on internal carbon stores to maintain colonization during periods of famine, we found that by providing a constant supply of a readily metabolized sugar, i.e., gluconate, in the animal's drinking water, the competitive disadvantage of E. coli glycogen metabolism mutants is rescued. The results suggest that glycogen storage may be widespread in enteric bacteria because it is necessary for maintaining rapid growth in the intestine, where there is intense competition for resources and occasional famine. An important implication of this study is that the sugars used by E. coli are present in limited quantities in the intestine, making endogenous carbon stores valuable. Thus, there may be merit to combating enteric infections by using probiotics or prebiotics to manipulate the intestinal microbiota in such a way as to limit the availability of sugars preferred by E. coli O157:H7 and perhaps other pathogens.

No abstract