Host translation machinery is not a barrier to phages that interact with both CPR and non-CPR bacteria

Abstract

ABSTRACT Within human microbiomes, Gracilibacteria, Absconditabacteria, and Saccharibacteria, members of Candidate Phyla Radiation (CPR), are increasingly correlated with human oral health and disease. We profiled the diversity of CRISPR-Cas systems in the genomes of these bacteria and sought phages that are capable of infecting them by matching their spacer inventories to large phage sequence databases. Gracilibacteria and Absconditabacteria recode the typical TGA stop codon to glycine and are putatively infected by phages that share their host’s alternate genetic code. Unexpectedly, however, other predicted phages of Gracilibacteria and Absconditabacteria do not use an alternative genetic code. Some of these phages may infect both alternatively coded CPR bacteria and standard-coded bacteria. These phages typically rely on other stop codons besides TGA and thus should be capable of producing viable gene products in either bacterial host type. By avoiding the acquisition of in-frame stop codons, these phages may have a broadened host range. Interestingly, we additionally predict that some phages of Saccharibacteria are targeted by spacers encoded in Actinobacteria, a phylum that includes known hosts for episymbiotic Saccharibacteria. IMPORTANCE Here, we profiled putative phages of Saccharibacteria, which are of particular importance as Saccharibacteria influence some human oral diseases. We additionally profiled putative phages of Gracilibacteria and Absconditabacteria, two Candidate Phyla Radiation (CPR) lineages of interest given their use of an alternative genetic code. Among the phages identified in this study, some are targeted by spacers from both CPR and non-CPR bacteria and others by both bacteria that use the standard genetic code as well as bacteria that use an alternative genetic code. These findings represent new insights into possible phage replication strategies and have relevance for phage therapies that seek to manipulate microbiomes containing CPR bacteria.