Phase-variable capsular polysaccharides and lipoproteins modify bacteriophage susceptibility in Bacteroides thetaiotaomicron

Abstract

A variety of cell surface structures dictate interactions between bacteria and their environment, including their viruses (bacteriophages). Members of the human gut Bacteroidetes characteristically produce several phase-variable capsular polysaccharides (CPS), but their contributions to bacteriophage interactions are unknown. To begin to understand how CPS impact Bacteroides -phage interactions, we isolated 71 B. thetaiotaomicron -infecting bacteriophages from two locations in the United States. Using B. thetaiotaomicron strains that express defined subsets of CPS, we show that CPS dictates host tropism for these phages and that expression of non-permissive CPS variants are selected under phage predation, enabling survival. In the absence of CPS, B. thetaiotaomicron escapes bacteriophage predation by altering expression of 8 distinct phase-variable lipoproteins. When constitutively expressed, one of these lipoproteins promotes resistance to multiple bacteriophages. Our results reveal important roles for Bacteroides CPS and other cell surface structures that allow these bacteria to persist under bacteriophage predation and hold important implications for using bacteriophages therapeutically to target gut symbionts.

Bacteriophage Resistance AffectsFlavobacterium columnareVirulence Partly via Mutations in Genes Related to Gliding Motility and Type IX Secretion System

“…Various mechanisms to regain phage resistance have been found also in fish pathogenic F. psychrophilum (23) and V. anguillarum (24), in which a rapid reversion back to phagesensitive phenotype has been shown to occur. This sort of dynamics in phage resistance has also been observed in a human symbiont Bacteroides thetaiotaomicron (37), suggesting that the phenomenon may be common among wide variety of bacteria. Phage-exposed F. columnare isolates F2R56, F2R66 and F9R58 did not respond to phage infection with surface modifications, but maintained their original rhizoid colony morphotype and high virulence.…”

Shining Light on Human Gut Bacteriophages

“…A phenomenon called phase variation is thought to be an important mediator of transient resistance that results in phenotypic variation in response to environmental conditions. Recently, the significance of phase variation in dictating phage-host interactions in the gut has become of interest (Jiang et al, 2019 ; Turkington et al, 2019 ; Porter et al, 2020 ). It occurs by variable expression of gene loci due to hypermutation or methylation resulting in genes being reversibly switched “on or off” (Bayliss, 2009 ).…”

“…Many gut bacteria are extremely difficult to culture, thus making isolation of their associated phages difficult (Browne et al, 2016). Furthermore, many phages are strain specific, mimicking gut conditions in vitro is problematic, and host factors such as phase variable expression of host receptors and the existence of multiple phage resistance mechanisms can add another level of complexity (Porter et al, 2020). This review will discuss our current understanding of the human gut phageome and gut phage-bacteria interactions.…”

Thousands of Previously Unknown Phages Discovered in Whole-community Human Gut Metagenomes

“…Glycosyltransferases are encoded within capsular polysaccharide biosynthetic loci [103] and phase variation of the capsular polysaccharides confers immunity from phages that rely on these molecules for adsorption [104]. The speci c roles of the HipA-family kinase, ATPase and glycosyltransferase are unknown but, collectively, these enzymes might modify host cell capsules, granting temporary immunity to heterotypic phage infection while the morphogenesis of "Gratiaviridae" progeny virions completes.…”