Escherichia coli is a single species consisting of many biotypes, some of which are commensal colonizers of mammals and others that cause disease. Humans are colonized on average with five commensal biotypes, and it is widely thought that the commensals serve as a barrier to infection by pathogens. Previous studies showed that a combination of three pre-colonized commensal E. coli strains prevents colonization of E. coli O157:H7 in a mouse model (Leatham, et al., 2010, Infect Immun 77: 2876–7886). The commensal biotypes included E. coli HS, which is known to successfully colonize humans at high doses with no adverse effects, and E. coli Nissle 1917, a human commensal strain that is used in Europe as a preventative of traveler's diarrhea. We hypothesized that commensal biotypes could exert colonization resistance by consuming nutrients needed by E. coli O157:H7 to colonize, thus preventing this first step in infection. Here we report that to colonize streptomycin-treated mice E. coli HS consumes six of the twelve sugars tested and E. coli Nissle 1917 uses a complementary yet divergent set of seven sugars to colonize, thus establishing a nutritional basis for the ability of E. coli HS and Nissle 1917 to occupy distinct niches in the mouse intestine. Together these two commensals use the five sugars previously determined to be most important for colonization of E. coli EDL933, an O157:H7 strain. As predicted, the two commensals prevented E. coli EDL933 colonization. The results support a model in which invading pathogenic E. coli must compete with the gut microbiota to obtain the nutrients needed to colonize and establish infection; accordingly, the outcome of the challenge is determined by the aggregate capacity of the native microbiota to consume the nutrients required by the pathogen.

The intestine is inhabited by a large microbial community consisting primarily of anaerobes and, to a lesser extent, facultative anaerobes, such as Escherichia coli, which we have shown requires aerobic respiration to compete successfully in the mouse intestine (S. A. Jones et al., Infect. Immun. 75:4891-4899, 2007). If facultative anaerobes efficiently lower oxygen availability in the intestine, then their sustained growth must also depend on anaerobic metabolism. In support of this idea, mutants lacking nitrate reductase or fumarate reductase have extreme colonization defects. Here, we further explore the role of anaerobic respiration in colonization using the streptomycin-treated mouse model. We found that respiratory electron flow is primarily via the naphthoquinones, which pass electrons to cytochrome bd oxidase and the anaerobic terminal reductases. We found that E. coli uses nitrate and fumarate in the intestine, but not nitrite, dimethyl sulfoxide, or trimethylamine N-oxide. Competitive colonizations revealed that cytochrome bd oxidase is more advantageous than nitrate reductase or fumarate reductase. Strains lacking nitrate reductase outcompeted fumarate reductase mutants once the nitrate concentration in cecal mucus reached submillimolar levels, indicating that fumarate is the more important anaerobic electron acceptor in the intestine because nitrate is limiting. Since nitrate is highest in the absence of E. coli, we conclude that E. coli is the only bacterium in the streptomycintreated mouse large intestine that respires nitrate. Lastly, we demonstrated that a mutant lacking the NarXL regulator (activator of the NarG system), but not a mutant lacking the NarP-NarQ regulator, has a colonization defect, consistent with the advantage provided by NarG. The emerging picture is one in which gene regulation is tuned to balance expression of the terminal reductases that E. coli uses to maximize its competitiveness and achieve the highest possible population in the intestine.The mouse colon is home to at least several hundred bacterial species and more than 100 billion bacteria per g of contents, a microbial community dominated by anaerobes with essentially no aerobes (2,38,57,68). It is becoming increasingly clear that facultative anaerobes consume oxygen and thereby modify their host environment. For example, kidney infection caused by uropathogenic Escherichia coli results in local ischemia (47). The facultatively anaerobic enteric pathogen Shigella flexneri responds to oxygen in the gut by modulating virulence gene expression (45). It has been postulated that the importance of Salmonella motility for chemotaxis through the mucus layer (61) may be due to aerotaxis (44). That E. coli requires cytochrome bd oxidase to gain a competitive advantage implies that the colon is not the anaerobic environment that many consider it to be (30). Here, we explore the possibility that efficient oxygen scavenging by E. coli in the intestine causes it to depend also on anaerobic respiration.To maximize their energy efficie...

Weakly electric freshwater fish use self-generated electric fields to image their worlds and communicate in the darkness of night and turbid waters. This active sensory/communication modality evolved independently in the freshwaters of South America and Africa, where hundreds of electric fish species are broadly and abundantly distributed. The adaptive advantages of the sensory capacity to forage and communicate in visually-unfavorable environments and outside the detection of visually-guided predators likely contributed to the broad success of these clades across a variety of Afrotropical and neotropical habitats. Here we consider the potentially high and limiting metabolic costs of the active sensory and communication signals that define the gymnotiform weakly electric fish of South America. Recent evidence from two well-studied species suggests that the metabolic costs of electrogenesis can be quite high, sometimes exceeding one-fourth of these fishes' daily energy budget. Supporting such an energetically expensive system has shaped a number of cellular, endocrine, and behavioral adaptations to restrain the metabolic costs of electrogenesis in general or in response to metabolic stress. Despite a suite of adaptations supporting electrogenesis, these weakly electric fish are vulnerable to metabolic stresses such as hypoxia and food restriction. In these conditions, fish reduce signal amplitude presumably as a function of absolute energy shortfall or as a proactive means to conserve energy. In either case, reducing signal amplitude compromises both sensory and communication performance. Such outcomes suggest that the higher metabolic cost of active sensing and communication in weakly electric fish compared with the sensory and communication systems in other neotropical fish might mean that weakly electric fish are disproportionately susceptible to harm from anthropogenic disturbances of neotropical aquatic habitats. Fully evaluating this possibility, however, will require broad comparative studies of metabolic energetics across the diverse clades of gymnotiform electric fish and in comparison to other nonelectric neotropical fishes.

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High-frequency action potentials (APs) allow rapid information acquisition and processing in neural systems, but create biophysical and metabolic challenges for excitable cells. The electric fish Eigenmannia virescens images its world and communicates with high-frequency (200-600 Hz) electric organ discharges (EODs) produced by synchronized APs generated at the same frequency in the electric organ cells (electrocytes). We cloned three previously unidentified Na+-activated K+ channel isoforms from electroctyes (eSlack1, eSlack2, and eSlick1). In electrocytes, mRNA transcript levels of the rapidly-activating eSlick, but not the slower eSlack1 or eSlack2, correlated with EOD frequency across individuals. In addition, transcript levels of an inward-rectifier K+ channel, a voltage-gated Na+ channel, and Na+,K+-ATPases also correlated with EOD frequency while a second Na+ channel isoform did not. Computational simulations showed that maintaining electrocyte AP waveform integrity as firing rates increase requires scaling conductances in accordance with these mRNA expression correlations, causing AP metabolic costs to increase exponentially.