Survival and Implantation of Escherichia coli in the Intestinal Tract

Abstract

A 0.5 ml inoculum introduced directly into the stomach of mice was cleared rapidly into the small intestine. Bicarbonate buffer, but not skim milk, protected such an inoculum from stomach acid until at least 90% of it had entered the small intestine. Passage and survival of various E. coli strains through the mouse gut were tested by introducing a buffered bacterial inoculum directly into the stomach with the following 2 intestinal tracers: Cr51Cl3 and spores of a thermophilic Bacillus sp. Quantitative recovery of excreted bacteria was accomplished by collecting the feces overnight in a refrigerated cage pan. Wild-type E. coli strains and E. coli K-12 were excreted rapidly (98-100% within 18 h) in the feces without overall multiplication or death. E. coli .chi. 1776 and DP50supF, i.e., strains certified for recombinant DNA experiments, underwent rapid death in vivo such that their excretion in the feces was reduced to .apprx. 1.1 and 4.7% of the inoculum, respectively. The acidity of the stomach had little bactericidal effect on the E. coli K-12 strain tested, but significantly reduced the survival of more acid-sensitive bacteria (Vibrio cholerae) under these conditions. Long-term implantation of E. coli strains into continuous-flow [CF] cultures of mouse cecal flora or into conventional mice was difficult. When the E. coli strain was first inoculated into sterile CF cultures or into germfree mice, which were subsequently associated with conventional mouse cecal flora, the E. coli strains persisted in a large proportion of the animals at levels resembling E. coli populations in conventional mice. Metabolic adaptation contributed only partially to the success of an E. coli inoculum that was first introduced. A mathematical model is described which explains this phenomenon on the basis of competition for adhesion sites, in which an advantage accrues to the bacterium which occupies those sites first. The mathematical model predicts that 2 bacterial strains that compete in the gut for the same limiting nutrient can coexist if the metabolically less efficient strains have specific adhesion sites available. The specific rate constant of E. coli growth in monoassociated gnotobiotic mice was 2.0 h-1; the excretion rate in conventional animals was -0.23 h-1. Consequently, limitation of growth must be the primary mechanism controlling bacterial populations in the large intestine. The beginnings of a general hypothesis of the ecology of the large intestine are proposed, in which the effects of the competitive metabolic interactions described earlier are modified by the effects of bacterial association with the intestinal wall.