PT - JOURNAL ARTICLE AU - Cole B. Matrishin AU - Elaine M. Haase AU - Floyd E. Dewhirst AU - Jessica L. Mark Welch AU - Fabiola Miranda-Sanchez AU - Donald C. MacFarland AU - Kathryn M. Kauffman TI - Phages are important unrecognized players in the ecology of the oral pathogen <em>Porphyromonas gingivalis</em> AID - 10.1101/2022.12.30.519816 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.12.30.519816 4099 - http://biorxiv.org/content/early/2022/12/31/2022.12.30.519816.short 4100 - http://biorxiv.org/content/early/2022/12/31/2022.12.30.519816.full AB - Background Porphyromonas gingivalis (hereafter “Pg”) is an oral pathogen that can act as a keystone driver of inflammation and periodontal disease. Although Pg is most readily recovered from individuals with actively progressing periodontal disease, healthy individuals and those with stable non-progressing disease are also colonized by Pg. Insights into the factors shaping the striking strain-level variation in Pg, and its variable associations with disease, are needed to achieve a more mechanistic understanding of periodontal disease and its progression. A key force shaping strain level diversity in all microbial communities is infection of bacteria by their viral (phage) predators and symbionts. Surprisingly, although Pg has been the subject of study for over 40 years, essentially nothing is known of its phages, and the prevailing paradigm is that phages are not important in the ecology of Pg.Results Here we systematically addressed the question of whether Pg are infected by phages - and we found that they are. We found that prophages are common in Pg, they are genomically diverse, and they encode genes that have the potential to alter Pg physiology and interactions. We found that phages represent unrecognized targets of the prevalent CRISPR-Cas defense systems in Pg, and that Pg strains encode numerous additional mechanistically diverse candidate anti-phage defense systems. We also found that phages and candidate anti-phage defense system elements together are major contributors to strain level diversity and the species pangenome of this oral pathogen. Finally, we demonstrate that prophages harbored by a model Pg strain are active in culture, producing extracellular viral particles in broth cultures.Discussion This work definitively establishes that phages are a major unrecognized force shaping the ecology and intraspecies strain-level diversity of the well-studied oral pathogen Pg. The foundational phage sequence datasets and model systems that we establish here add to the rich context of all that is already known about Pg, and point to numerous avenues of future inquiry that promise to shed new light on fundamental features of phage impacts on human health and disease broadly.Competing Interest StatementThe authors have declared no competing interest.