Nutritional Basis for Colonization Resistance by Human Commensal Escherichia coli Strains HS and Nissle 1917 against E. coli O157:H7 in the Mouse Intestine

Abstract

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.

Escherichia coli EDL933 Requires Gluconeogenic Nutrients To Successfully Colonize the Intestines of Streptomycin-Treated Mice Precolonized with E. coli Nissle 1917

“…1). Since we already have established that E. coli Nissle 1917 uses glycolytic nutrients for colonization (14), these results also suggest that E. coli Nissle 1917 uses both glycolytic and gluconeogenic nutrients for growth in the mouse intestine between day 1 and day 5 postfeeding. Beyond day 5 postfeeding, the ratio of E. coli Nissle 1917 to E. coli Nissle 1917 ⌬ppsA ⌬pckA remained fairly constant (Fig.…”

“…It is also known that E. coli strains reside in mucus as members of mixed biofilms (12,13). Furthermore, E. coli strains use monoand disaccharides as glycolytic nutrients for growth in the mouse large intestine (14,37), yet mono-and disaccharides are absorbed in the small intestine. Since most E. coli strains do not secrete extracellular polysaccharide hydrolases (38)(39)(40) and therefore cannot degrade dietary-fiber-derived and mucin-derived oligoand polysaccharides, it is likely that during long-term colonization, E. coli depends on the anaerobes in mucus that can degrade oligo-and polysaccharides, e.g., Bacteroides thetaiotaomicron (41), to provide them with the mono-and disaccharides they use for growth.…”

“…Humans infected with E. coli O157:H7 strains are presumably colonized with at least one commensal E. coli strain prior to infection. To mimic that situation, streptomycin-treated mice can be precolonized with a commensal E. coli strain for 10 days and then fed E. coli EDL933 (14,36). When mice were precolonized with the commensal E. coli strain MG1655 for 10 days and were then fed 10 5 CFU each of wild-type E. coli EDL933 and E. coli EDL933 ⌬ppsA ⌬pckA, wild-type E. coli EDL933 grew to a level between 10 6 and 10 7 CFU/g of feces, whereas E. coli EDL933 ⌬ppsA ⌬pckA dropped to about 10 3 CFU/g of feces ( Fig.…”

“…The streptomycin-treated mouse model is used routinely for this purpose, since streptomycin-treated mice fulfill these criteria (10,11). Using this model, we have shown that for E. coli to colonize, it must obtain nutrients in the mucus layer, which overlies the epithelium (10,11), that it resides in the mucus layer as a member of mixed biofilms (12,13), and that each E. coli strain displays a unique nutritional program in the intestine (14).…”

Bacteria–bacteria interactions within the microbiota of the ancestral metazoan Hydra contribute to fungal resistance

“…Several mechanisms have been proposed to explain such symbiont-mediated interference with the growth of pathogens (Haine, 2008;Hamilton and Perlman, 2013). These involve exploitative competition between symbionts and pathogens for limiting factors such as nutrients (Maltby et al, 2013) and adhesion receptors (Juge, 2012). Furthermore, beneficial microbes can stimulate the host's immune system against potential pathogens (Vaishnava et al, 2008), a mechanism analogous to apparent competition, in which an increase in one species causes an increase in a predator that negatively affects a competitor (Holt, 1977).…”