{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T17:23:47Z","timestamp":1793035427361,"version":"4.5.0"},"reference-count":80,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Republic of Kazakhstan","award":["BR24992760"],"award-info":[{"award-number":["BR24992760"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Bacteria with similar genomes can exhibit different phenotypes due to alternative gene expression patterns. In this study, we analysed four antibiotic-resistant <jats:italic>Staphylococcus aureus<\/jats:italic> hospital isolates using transcriptomics, PacBio genome sequencing, and methylomics analyses. Transcriptomic data were obtained from cultures exposed to gentamicin, the iodine-alanine complex CC-196, and their combination. We observed strain-specific expression patterns of core and accessory genes that remained stable under antimicrobial stress \u2013 a phenomenon we term the Clonal Gene Expression Stability (CGES) that is the main discovery of the paper. An involvement of epigenetic mechanisms in stabilization of the CGES was hypothesized and statistically verified. Canonical methylation patterns controlled by type I restriction-modification systems accounted for\u2009~\u200910% of epigenetically modified adenine residues, whereas multiple non-canonically modified adenines were distributed sporadically due to imperfect DNA targeting by methyltransferases. Protein-coding sequences were characterized by a significantly lower frequency of modified nucleotides. Epigenetic modifications near transcription start codons showed a statistically significant negative association with gene expression levels. While the role of epigenetic modifications in gene regulation remains debatable, variations in non-canonical modification patterns may serve as markers of CGES.<\/jats:p>","DOI":"10.1371\/journal.pone.0322006","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T17:27:51Z","timestamp":1746466071000},"page":"e0322006","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Epigenetic background of lineage-specific gene expression landscapes of four Staphylococcus aureus hospital isolates"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0397-7840","authenticated-orcid":true,"given":"Ilya S.","family":"Korotetskiy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9490-9300","authenticated-orcid":true,"given":"Sergey V.","family":"Shilov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4186-3948","authenticated-orcid":true,"given":"Tatyana V.","family":"Kuznetsova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6436-803X","authenticated-orcid":true,"given":"Natalya","family":"Zubenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7194-0556","authenticated-orcid":true,"given":"Lyudmila","family":"Ivanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5459-2772","authenticated-orcid":true,"given":"Oleg N.","family":"Reva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,5,5]]},"reference":[{"issue":"9","key":"pone.0322006.ref001","doi-asserted-by":"crossref","first-page":"e1001125","DOI":"10.1371\/journal.ppat.1001125","article-title":"Molecular and evolutionary bases of within-patient genotypic and phenotypic diversity in Escherichia coli extraintestinal infections","volume":"6","author":"M Levert","year":"2010","journal-title":"PLoS Pathog"},{"issue":"1","key":"pone.0322006.ref002","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s13213-022-01677-5","article-title":"High-throughput sequencing analysis reveals genomic similarity in phenotypic heterogeneous Photorhabdus luminescens cell populations","volume":"72","author":"N Dominelli","year":"2022","journal-title":"Ann Microbiol"},{"issue":"1","key":"pone.0322006.ref003","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41579-019-0286-2","article-title":"The bacterial epigenome","volume":"18","author":"MA S\u00e1nchez-Romero","year":"2020","journal-title":"Nat Rev Microbiol"},{"issue":"1","key":"pone.0322006.ref004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1134\/S1022795422010124","article-title":"Epigenetic mechanisms of gene expression regulation in bacteria of the Genus Bacillus","volume":"58","author":"NG Vasilchenko","year":"2022","journal-title":"Russian J Gen"},{"issue":"1","key":"pone.0322006.ref005","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/epigenomes7010001","article-title":"Environmental adaptation of genetically uniform organisms with the help of epigenetic mechanisms - 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