{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T21:30:11Z","timestamp":1784323811360,"version":"3.55.0"},"reference-count":76,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JPJSCCB20230005"],"award-info":[{"award-number":["JPJSCCB20230005"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Despite being a commensal bacterium, Cutibacterium acnes has been widely considered a major opportunistic pathogen due to its capacity for biofilm production and inflammatory induction, causing device-related, post-implant infections, and skin inflammatory diseases. In this study, we isolated and characterised the novel bacteriophage Cutibacterium acnes phage KIT09 as a potential antimicrobial candidate for the treatment of Cutibacterium acnes-related infections such as acne vulgaris and postsurgical infections. Subsequently, phage-resistant bacterial mutants were generated through phage KIT09 exposure and characterised. Wastewater samples were collected for the isolation of C. acnes phages, followed by their characterisation using C. acnes National Institute of Technology and Evaluation (NITE) Biological Resources Center (NBRC) 107605 (phylotype IA1). Resistant mutants were isolated after prolonged exposure of the newly isolated phage to host bacteria and then characterised. A novel C. acnes phage, designated KIT09, was isolated, demonstrating prolonged bacteriolysis lasting up to 96 h at a multiplicity of infection of 10, and exhibiting high thermal and pH stability. Following sustained selective pressure by phage KIT09, three phage-resistant bacterial isolates were obtained, forming smaller colonies than the wild-type strain, but maintaining a high phage adsorption capacity (&gt;90% after 20 min). Whole-genome sequencing revealed 12 nucleotide mutations across five genes, including six non-synonymous substitutions. Three genes encoding a two-component histidine kinase, DNA processing protein A (DprA), and a ThuA-containing domain protein were mutated in all resistant isolates. Characterisation of the novel phage KIT09 demonstrated its robust lytic activity and environmental stability against C. acnes phylotype IA1. Isolated resistant mutants retained high phage adsorption, accompanied by recurrent mutations in genes encoding a two-component histidine kinase, DprA, and a ThuA-domain protein, suggesting the presence of alternative, CRISPR-Cas\u2013independent resistance mechanisms in C. acnes.<\/jats:p>","DOI":"10.3390\/ijms262412166","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T11:08:28Z","timestamp":1766056108000},"page":"12166","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Characterisation of the Novel Cutibacterium acnes Phage KIT09 and First Report of CRISPR-Cas-Independent Bacteriophage Resistance in Phylotype IA1"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5527-7360","authenticated-orcid":false,"given":"Phuoc-Dung","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Functional Chemistry, Kyoto Institute of Technology, Kyoto 606-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koki","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Department of Functional Chemistry, Kyoto Institute of Technology, Kyoto 606-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan Pham-Khanh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"College of Natural Sciences, Can Tho University, Campus II, 3\/2 Street, Can Tho 94000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5216-2282","authenticated-orcid":false,"given":"Hoang Viet","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Faculty of Medical Technology, Hanoi Medical University, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Kitao","sequence":"additional","affiliation":[{"name":"Antimicrobial Technology Co., Ltd., Kyoto 601-8145, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanao","family":"Yoshimoto","sequence":"additional","affiliation":[{"name":"Antimicrobial Technology Co., Ltd., Kyoto 601-8145, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7496-4692","authenticated-orcid":false,"given":"Kaeko","family":"Kamei","sequence":"additional","affiliation":[{"name":"Department of Functional Chemistry, Kyoto Institute of Technology, Kyoto 606-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1038\/jid.2013.21","article-title":"Propionibacterium acnes strain populations in the human skin microbiome associated with acne","volume":"133","author":"Tomida","year":"2013","journal-title":"J. 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