{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T02:00:46Z","timestamp":1783389646676,"version":"3.54.6"},"posted":{"date-parts":[[2025,9,15]]},"group-title":"Genomics","reference-count":75,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Despite\n                  <jats:italic>Cutibacterium acnes<\/jats:italic>\n                  being the most abundant and prevalent bacteria on human skin, only a single type of phage has been identified that infects this host. Here, we leverage this one-to-one system to systematically characterize how the phage-bacteria arms race shapes\n                  <jats:italic>C. acnes<\/jats:italic>\n                  evolution and community composition on individual people. Our analysis reveals a surprising lack of phage-mediated selection despite global prevalence of\n                  <jats:italic>C. acnes<\/jats:italic>\n                  phages. Analysis of anti-phage defense systems across 3,205 bacterial genomes revealed a limited, phylogenetically restricted defense repertoire under weak selective pressure to diversify or be maintained. Functional assays did not reveal alternative phage resistance mechanisms or fitness costs associated with defense gene carriage that could explain this limited immune arsenal. This lack of pressure to maintain phage resistance could not be explained by lack of phage colonization, as examination of 471 global human facial skin metagenomes demonstrated that even in samples with high virus-to-microbe ratio, phage-sensitive clades dominate on-person populations. Together, these findings indicate that phage pressure, while present, does not play a critical role in determining strain fitness and success within\n                  <jats:italic>C. acnes<\/jats:italic>\n                  populations on human skin. We propose that this observed weak phage-mediated selective pressure can be explained by the anatomy of skin:\n                  <jats:italic>C. acnes<\/jats:italic>\n                  growth is thought to occur at the bottom of pores, where exposure to phage may be limited by physical barriers. Together, this portrait of a static arms race provides a strong contrast with other microbial species in different ecosystems and expands understanding of phage-bacteria interactions in the human microbiome.\n                <\/jats:p>","DOI":"10.1101\/2025.09.09.675206","type":"posted-content","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T03:55:14Z","timestamp":1757994914000},"source":"Crossref","is-referenced-by-count":1,"title":["Phage-mediated lysis does not determine\n                  <i>Cutibacterium acnes<\/i>\n                  colonization on human skin"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8611-7207","authenticated-orcid":false,"given":"A. Delphine","family":"Tripp","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5079-0690","authenticated-orcid":false,"given":"Evan B.","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishaq","family":"Balogun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Brodsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0249-5014","authenticated-orcid":false,"given":"Jacob S.","family":"Baker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3974-3480","authenticated-orcid":false,"given":"Christopher P.","family":"Mancuso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5831-5895","authenticated-orcid":false,"given":"Simon","family":"Roux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8926-3875","authenticated-orcid":false,"given":"Fatima A.","family":"Hussain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1681-2313","authenticated-orcid":false,"given":"Tami D.","family":"Lieberman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025091820200956000_2025.09.09.675206v1.1","doi-asserted-by":"crossref","first-page":"3950","DOI":"10.3390\/ijms24043950","article-title":"The skin microbiome: current landscape and future opportunities","volume":"24","year":"2023","journal-title":"International journal of molecular sciences"},{"key":"2025091820200956000_2025.09.09.675206v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-025-01211-9"},{"key":"2025091820200956000_2025.09.09.675206v1.3","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13073-020-00765-y","article-title":"Strain-level epidemiology of microbial communities and the human microbiome","volume":"12","year":"2020","journal-title":"Genome medicine"},{"key":"2025091820200956000_2025.09.09.675206v1.4","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.83479"},{"key":"2025091820200956000_2025.09.09.675206v1.5","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1146\/annurev-virology-091919-075914","article-title":"Understanding the Impacts of Bacteriophage Viruses: From Laboratory Evolution to Natural Ecosystems","volume":"9","year":"2022","journal-title":"Annu. 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