Precolonized human commensal Escherichia coli strains serve as a barrier to E. coli O157:H7 growth in the streptomycin-treated mouse intestine

Abstract

Different Escherichia coli strains generally have the same metabolic capacity for growth on sugars in vitro, but they appear to use different sugars in the streptomycin-treated mouse intestine (Fabich et al., Infect. Immun. 76:1143-1152, 2008). Here, mice were precolonized with any of three human commensal strains (E. coli MG1655, E. coli HS, or E. coli Nissle 1917) and 10 days later were fed 10(5) CFU of the same strains. While each precolonized strain nearly eliminated its isogenic strain, confirming that colonization resistance can be modeled in mice, each allowed growth of the other commensal strains to higher numbers, consistent with different commensal E. coli strains using different nutrients in the intestine. Mice were also precolonized with any of five commensal E. coli strains for 10 days and then were fed 10(5) CFU of E. coli EDL933, an O157:H7 pathogen. E. coli Nissle 1917 and E. coli EFC1 limited growth of E. coli EDL933 in the intestine (10(3) to 10(4) CFU/gram of feces), whereas E. coli MG1655, E. coli HS, and E. coli EFC2 allowed growth to higher numbers (10(6) to 10(7) CFU/gram of feces). Importantly, when E. coli EDL933 was fed to mice previously co-colonized with three E. coli strains (MG1655, HS, and Nissle 1917), it was eliminated from the intestine (<10 CFU/gram of feces). These results confirm that commensal E. coli strains can provide a barrier to infection and suggest that it may be possible to construct E. coli probiotic strains that prevent growth of pathogenic E. coli strains in the intestine.

FIG. 1.

A precolonized E. coli strain prevents the same strain from colonizing the mouse intestine. Sets of three mice were fed 10⁵ CFU of a human commensal strain and 10 days later were fed 10⁵ CFU of the same strain. (A) E. coli MG1655 Str^r (▪) and, 10 days later, E. coli MG1655 Str^r Nal^r (▴). (B) E. coli HS Str^r (▪) and, 10 days later, E. coli HS Str^r Nal^r (▴). (C) E. coli Nissle 1917 Str^r Nal^r (▪) and, 10 days later, 10⁵ CFU of E. coli Nissle 1917 Str^r Rif^r (▴). At the indicated times, fecal samples were homogenized, diluted, and plated as described in Materials and Methods. Data from two independent experiments (six mice) are shown. Bars represent the standard errors of the log₁₀ means of CFU per gram of feces for six mice.

FIG. 2.

E. coli human commensal strains can colonize the intestines of mice precolonized with different human E. coli commensal strains. (A) Sets of three mice were fed 10⁵ CFU of E. coli MG1655 Str^r (▪) and, 10 days later, were fed 10⁵ CFU of E. coli HS Str^r Nal^r (▴). (B) Sets of three mice were fed 10⁵ CFU of E. coli MG1655 Str^r Nal^r (▪) and, 10 days later, were fed 10⁵ CFU of E. coli Nissle 1917 Str^r Rif^r (▴). (C) Sets of three mice were fed 10⁵ CFU of E. coli HS Str^r (▪) and, 10 days later, were fed 10⁵ CFU of E. coli MG1655 Str^r Nal^r (▴). (D) Sets of three mice were fed 10⁵ CFU of E. coli HS Str^r Nal^r (▪) and, 10 days later, were fed 10⁵ CFU of E. coli Nissle 1917 Str^r Rif^r (▴). (E) Sets of three mice were fed 10⁵ CFU of E. coli Nissle 1917 Str^r Rif^r (▪) and, 10 days later, were fed 10⁵ CFU of E. coli MG1655 Str^r Nal^r (▴). (F) Sets of three mice were fed 10⁵ CFU of E. coli Nissle 1917 Str^r Rif^r (▪) and, 10 days later, were fed 10⁵ CFU of E. coli HS Str^r Nal^r (▴). Data were collected and plotted as described in the legend to Fig. 1.

FIG. 3.

E. coli EDL933 colonization of the mouse intestine precolonized with different commensal strains. (A) Sets of three mice were fed 10⁵ CFU of E. coli HS Str^r Nal^r (▪) and, 10 days later, were fed 10⁵ CFU of E. coli EDL933 Str^r Rif^r (▴). (B) Sets of three mice were fed 10⁵ CFU of E. coli MG1655 Str^r Nal^r (▪) and, 10 days later, were fed 10⁵ CFU of E. coli EDL933 Str^r Rif^r (▴). (C) Sets of three mice were fed 10⁵ CFU of E. coli EFC2 Str^r (▪) and, 10 days later, were fed 10⁵ CFU of E. coli EDL933 Str^r Rif^r (▴). (D) Sets of three mice were fed 10⁵ CFU of E. coli EFC1 Str^r (▪) and, 10 days later, were fed 10⁵ CFU of E. coli EDL933 Str^r Rif^r (▴). (E) Sets of three mice were fed 10⁵ CFU of E. coli Nissle Str^r Nal^r (▪) and, 10 days later, were fed 10⁵ CFU of E. coli EDL933 Str^r Rif^r (▴). (F) Sets of three mice were fed 10⁵ CFU of E. coli HS Str^r (▪), E. coli MG1655 Str^r Nal^r (•), and E. coli Nissle 1917 Str^r ΔlacZ::cat (▵) and, 10 days later, were fed 10⁵ CFU of E. coli EDL933 Str^r Rif^r (▴). Data were collected and plotted as described in the legend to Fig. 1.