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

• Published in: bioRxiv
• Main Authors: Berryhill, Brandon A, Burke, Kylie B, Fontaine, Jake, Brink, Catherine E, Harvill, Mason G, Goldberg, David A, Konstantinidis, Konstantinos T, Levin, Bruce R, Woodworth, Michael H
• Format: Journal Article
• Language: English
• Published: United States 02.07.2024
• Subjects: Escherichia coli; O antigens; Bacteriophage; Enteric Microbiome; Phage Resistance; Fecal Microbiota Transplantation; Population Biology
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2023.11.08.566299

There is a surfeit of bioinformatic data showing that bacteriophages abound in the enteric microbiomes of humans. What is the contribution of these viruses in shaping the bacterial strain and species composition of the gut microbiome and how are these phages maintained over time? To address these questions, we performed experiments with and phages isolated from four fecal microbiota transplantation (FMT) doses as representative samples of non-dysbiotic enteric microbiota and develop and analyze the properties of a mathematical model of the population and evolutionary dynamics of bacteria and phage. Our models predict and experiments confirm that due to production of the O antigen, in the enteric microbiome are likely to be resistant to infection with co-occurring phages. Furthermore, our modeling suggests that the phages can be maintained in the population due to the high rates of host transition between resistant and sensitive states, which we call leaky resistance. Based on our observations and model predictions, we postulate that the phages found in the human gut are likely to play little role in shaping the composition of at the strain level in the enteric microbiome in healthy individuals. How general this is for other species of bacteria in the enteric flora is not yet clear, although O antigen expression is common across many taxa.