Lytic Bacteroides uniformis bacteriophages exhibiting host tropism congruent with diversity generating retroelement

Intestinal phages are abundant and important component of gut microbiota, but our knowledge remains limited to only a few isolated and characterized representatives targeting numerically dominant gut bacteria. Here we describe isolation of human intestinal phages infecting Bacteroides uniformis. Bacteroides is one of the most common bacterial groups in the global human gut microbiota, however, to date not many Bacteroides specific phages are known. Phages isolated in this study belong to a novel viral genus, Bacuni, within Siphoviridae family and represent the first lytic phages, genomes of which encode diversity generating retroelements (DGR). This region is assumed to promote phage adaptation to the rapidly changing environmental conditions and to broaden its host range. Three isolated phages showed 99,83% genome identity but infected distinct B. uniformis strains. The tropism of Bacuni phages appeared to be dependent on the interplay of DGR mediated sequence variations of phage fimbrial tip proteins and mutations in host genes coding for outer-membrane proteins. We found prophages with up to 85% aa similarity to Bacuni phages in the genomes of B. acidifaciens and Prevotella sp.. Despite the abundance of Bacteroides within human microbiome, we found Bacuni phages only in a limited subset of published gut metagenomes. ImportanceThe lack of common marker gene in viruses require a precise characterization of diverse isolated phages to enhance metagenomic analyses and to understand their role in gut microbiota. Here we report the isolation of phages representing a new genus with characteristics so far not known or rarely described in intestinal phages. They are the first lytic phages specific for Bacteroides uniformis, a bacterial representative of the prevalent genus in the gut of humans and animals. Additionally, they are the first lytic phages containing specific regions (diversity generating retroelement) that putatively influence host tropism. The ability to switch constantly the targeted populations of the host species could provide an evolutionary advantage to these bacteriophages and may affect intra species diversity.