Responses of the Human Gut Escherichia coli Population to Pathogen and Antibiotic Disturbances

Research on human-associated E. coli tends to focus on pathogens, such as enterotoxigenic E. coli (ETEC) strains, which are a leading cause of diarrhea in developing countries. However, the severity of disease caused by these pathogens is thought to be influenced by the microbiome. The nonpathogenic E. coli community that resides in the human gastrointestinal tract may play a role in pathogen colonization and disease severity and may become a reservoir for virulence and antibiotic resistance genes. Our study used whole-genome sequencing of E. coli before, during, and after challenge with an archetype ETEC isolate, H10407, and antibiotic treatment to explore the diversity and resiliency of the resident E. coli population in response to the ecological disturbances caused by pathogen invasion and antibiotic treatment. ABSTRACT Studies of Escherichia coli in the human gastrointestinal tract have focused on pathogens, such as diarrhea-causing enterotoxigenic E. coli (ETEC), while overlooking the resident, nonpathogenic E. coli community. Relatively few genomes of nonpathogenic E. coli strains are available for comparative genomic analysis, and the ecology of these strains is poorly understood. This study examined the diversity and dynamics of resident human gastrointestinal E. coli communities in the face of the ecological challenges presented by pathogen (ETEC) challenge, as well as of antibiotic treatment. Whole-genome sequences obtained from E. coli isolates from before, during, and after ETEC challenge were used in phylogenomic and comparative genomic analyses to examine the diversity of the resident E. coli communities, as well as the dynamics of the challenge strain, H10407, a well-studied ETEC strain (serotype O78:H11) that produces both heat-labile and heat-stable enterotoxins. ETEC failed to become the dominant E. coli clone in two of the six challenge subjects, each of whom exhibited limited or no clinical presentation of diarrhea. The E. coli communities of the remaining four subjects became ETEC dominant during the challenge but reverted to their original, subject-specific populations following antibiotic treatment, suggesting resiliency of the resident E. coli population following major ecological disruptions. This resiliency is likely due in part to the abundance of antibiotic-resistant ST131 E. coli strains in the resident populations. This report provides valuable insights into the potential interactions of members of the gastrointestinal microbiome and its responses to challenge by an external pathogen and by antibiotic exposure. IMPORTANCE Research on human-associated E. coli tends to focus on pathogens, such as enterotoxigenic E. coli (ETEC) strains, which are a leading cause of diarrhea in developing countries. However, the severity of disease caused by these pathogens is thought to be influenced by the microbiome. The nonpathogenic E. coli community that resides in the human gastrointestinal tract may play a role in pathogen colonization and disease severity and may become a reservoir for virulence and antibiotic resistance genes. Our study used whole-genome sequencing of E. coli before, during, and after challenge with an archetype ETEC isolate, H10407, and antibiotic treatment to explore the diversity and resiliency of the resident E. coli population in response to the ecological disturbances caused by pathogen invasion and antibiotic treatment.