RT Journal Article SR Electronic T1 Host translation machinery is not a barrier to phages that infect both CPR and non-CPR bacteria JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.11.22.517103 DO 10.1101/2022.11.22.517103 A1 Jett Liu A1 Alexander L. Jaffe A1 LinXing Chen A1 Batbileg Bor A1 Jillian F. Banfield YR 2022 UL http://biorxiv.org/content/early/2022/11/23/2022.11.22.517103.abstract AB 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 comparing their spacer inventories to large phage sequence databases. Gracilibacteria and Absconditabacteria recode the typical TGA stop codon to glycine and are 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 are predicted to infect both alternatively coded CPR bacteria and standard coded bacteria. These phages rely on other stop codons besides TGA, and thus should be capable of producing viable gene products in either bacterial host type. Interestingly, we predict that phages of Saccharibacteria can replicate in Actinobacteria, which have been shown to act as episymbiotic hosts for Saccharibacteria. Overall, the broad host range of some CPR phages may be advantageous for the production of these phages for microscopic characterization or use as therapy agents, given the current difficulty of CPR cultivation. Absconditabacteria phages and Gracilibacteria phages may have avoided acquisition of in-frame stop codons to increase the diversity of bacteria in which they can replicate.Competing Interest StatementJFB is a co-founder of Metagenomi.