Adaptation to bile and anaerobicity limitsVibrio choleraephage adsorption

Abstract

AbstractBacteriophages (viruses of bacteria) play a pivotal role in shaping both the evolution and dynamics of bacterial populations. Bacteria employ arsenals of genetically encoded phage defense systems, but can alternatively achieve protection by changing the availability of cellular resources that phages rely on for propagation. These physiological changes are often adaptive responses to unique environmental signals. The facultative pathogenVibrio choleraeadapts to both aquatic and intestinal environments with niche-specific physiological changes that ensure its evolutionary success in such disparate settings. In both niches,V. choleraeis susceptible to predation by lytic phages like ICP1. However, both phages and susceptible bacterial hosts coexist in nature, indicating that environmental cues may modulateV. choleraecell state to protect against phage infection. This work explores one such modification in response to the intestine-specific signals of bile and anaerobicity. We found thatV. choleraegrown in these conditions reduces O1-antigen decoration on its outer membrane lipopolysaccharide. Because the O1-antigen is an essential moiety for ICP1 phage infection, we investigated the effect of partial O1-antigen depletion as a mechanism of phage defense and observed that O1-depletion limits phage adsorption. We identified mechanistic contributions to O1-depletion, including the essentiality of a weak acid tolerance system for O1 production at low pH, and alterations in transcriptional profiles indicating limitations in resources for O1-biosynthesis. This analysis illustrates a complex interplay between signals relevant to the intestinal environment and bacterial physiology that provideV. choleraewith protection from phage predation.