Infection with novelBacteroides phage BV01alters host transcriptome and bile acid metabolism in a common human gut microbe

Abstract

24The bacterial genus Bacteroides is among the most abundant and common taxa in the 25 human gut, yet little is known about the phages infecting the group. Bacteroides phage 26 BV01 (BV01) was identified as a prophage integrated on the chromosome of its host, 27Bacteroides vulgatus ATCC 8482. Phage BV01 is actively produced, and infects 28 susceptible B. vulgatus hosts in the mouse gut. Infection with BV01 causes a generalized 29 repression of the B. vulgatus transcriptome, downregulating 103 transcripts and 30 upregulating only 12. Integration of BV01 disrupts the promoter sequence of a 31 downstream gene encoding a putative tryptophan-rich sensory protein (tspO). Deletion of 32 tspO and subsequent RNAseq analysis revealed that more than half of the differentially-33 regulated transcripts are shared with the BV01 lysogen, suggesting the transcriptomic 34 response to BV01 is linked to tspO. Among these differentially-regulated transcripts are 35 two encoding bile salt hydrolases. Bile acid deconjugation assays show that BV01 36 represses its host's ability to hydrolyze bile acids in a tspO-dependent manner. Analysis 37 of 256 published healthy human gut metagenomes suggests that phage integration 38 adjacent to B. vulgatus-like tspO genes is rare within an individual, but common among 39 humans. Finally, this work proposes a novel phage family that includes BV01, the 40 Salyersviridae, whose host range spans the Bacteroides and is detectable in human-41 associated samples. Together, these findings highlight the importance of phage-host 42 interactions to our understanding of how gut microbes sense and interact with their 43 environment. 44 45 IMPORTANCE 46 3