Horizontal gene transfer overrides mutation in Escherichia coli colonizing the mammalian gut

Significance

Colonization of the mammalian gut by trillions of commensal bacteria starts early in life and contributes to host health. However, colonization by pathogens can be the launching pad for infection. Bacterial evolution has been studied mainly under laboratory conditions or in a disease context, but we understand less the evolutionary mechanisms of commensal bacteria in a healthy host microbiome. To fill this gap, we studied real-time gut colonization by Escherichia coli in healthy mice. We observe rapid evolution of the colonizing E. coli strain by bacteriophage-mediated horizontal gene transfer, which overrides the classical evolutionary mode of mutation accumulation. By experiments and mathematical modeling, we show that bacteriophage-mediated selection can produce complex evolutionary outcomes, including the emergence of a new commensal strain.

Abstract

Bacteria evolve by mutation accumulation in laboratory experiments, but tempo and mode of evolution in natural environments are largely unknown. Here, we study the ubiquitous natural process of host colonization by commensal bacteria. We show, by experimental evolution of Escherichia coli in the mouse intestine, that the ecology of the gut controls the pace and mode of evolution of a new invading bacterial strain. If a resident E. coli strain is present in the gut, the invading strain evolves by rapid horizontal gene transfer (HGT), which precedes and outweighs evolution by accumulation of mutations. HGT is driven by 2 bacteriophages carried by the resident strain, which cause an epidemic phage infection of the invader. These dynamics are followed by subsequent evolution by clonal interference of genetically diverse lineages of phage-carrying (lysogenic) bacteria. We show that the genes uptaken by HGT enhance the metabolism of specific gut carbon sources and provide a fitness advantage to lysogenic invader lineages. A minimal dynamical model explains the temporal pattern of phage epidemics and the complex evolutionary outcome of phage-mediated selection. We conclude that phage-driven HGT is a key eco-evolutionary driving force of gut colonization—it accelerates evolution and promotes genetic diversity of commensal bacteria.