Enteric Populations of Escherichia coli are Likely to be Resistant to Phages Due to O Antigen Production

Abstract

Metagenomic data provide evidence that bacteriophage (phage) abound in the enteric microbiomes of humans. However, the contribution of these viruses in shaping the bacterial composition of the gut microbiome and how these phages are maintained remains unclear. We performed experiments with 751 combinations of 54 Escherichia coli and 9 phage isolates from four fecal microbiota transplantation (FMT) doses and 5 laboratory phages as samples of non-dysbiotic human enteric microbiota. We also developed a mathematical model of the population and evolutionary dynamics of bacteria and phage. Our experiments predict that as a consequence of the production of the O-antigen, most of the E. coli in the human enteric microbiome will be resistant to infections with the array of co-occurring phages. Our modeling suggests that phages are maintained in these enteric communities due to the high rates of transition between the resistant and sensitive states resulting from O-antigen production or spontaneous O-antigen loss, respectively. Based on our observations and predictions from this theory, we postulate that the phage found in the human gut are likely to play little role shaping the strain composition of E. coli of healthy individuals. Although we only investigated E. coli, the mechanism of resistance described here is shared among most of the Gram-negative bacteria. Extended AbstractEvidence is provided that as a consequence of O-antigen-mediated resistance, the genetically diverse array of bacteriophage in the gut microbiome of humans play little or no role in determining the densities and distribution of genetically diverse strain E. coli in this habitat. Our mathematical model predicts, and our experiments support the hypothesis that the phage present in the gut microbiome are maintained by replication on the minority of sensitive bacteria generated by the leakiness of O-antigen-mediated resistance.