{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T15:55:48Z","timestamp":1776009348499,"version":"3.50.1"},"posted":{"date-parts":[[2024,7,11]]},"group-title":"Microbiology","reference-count":56,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T00:00:00Z","timestamp":1720656000000},"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":[[2025,3,4]]},"abstract":"<jats:p>\n                  SSR42 is the longest noncoding RNA in the\n                  <jats:italic>S. aureus<\/jats:italic>\n                  cell and the second-most abundant transcript in the stationary phase transcriptome, second only to RNAIII. It is highly conserved across strains and exhibits pronounced stability in stationary phase, however the mechanism behind its regulatory role has yet to be fully elucidated. Herein, we used transcriptomic and proteomic approaches to probe the role of SSR42, revealing that it is a powerful, novel activator of the primary leukocidin LukAB. SSR42 is required for cytotoxicity towards, and escape from within, human neutrophils, and also mediates survival within human blood. We show that SSR42 wields this role via derepression by the peroxide repressor PerR in response to the presence of human neutrophils and governs\n                  <jats:italic>lukAB<\/jats:italic>\n                  induction in this niche. Importantly, this regulation is driven by direct RNA-RNA interaction, as we show binding of the 5\u2032 UTR of the\n                  <jats:italic>lukAB<\/jats:italic>\n                  transcript with the 3\u2032 end of SSR42, which ultimately modulates transcript stability as well as translational activity. Finally, we demonstrate that this behavior is absolutely required for full virulence of\n                  <jats:italic>S. aureus<\/jats:italic>\n                  in murine models of both pneumonia and sepsis. Collectively, we present SSR42 as a pleiotropic regulatory RNA that acts as a nexus between environmental sensing and the regulation of pathogenesis, responding to environmental stimuli and host immune factors to bolster cytotoxic behavior and facilitate infection in\n                  <jats:italic>S. aureus<\/jats:italic>\n                  .\n                <\/jats:p>","DOI":"10.1101\/2024.07.11.603084","type":"posted-content","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T00:40:22Z","timestamp":1720744822000},"source":"Crossref","is-referenced-by-count":2,"title":["SSR42 is a Novel Regulator of Cytolytic Activity in\n                  <i>Staphylococcus aureus<\/i>"],"prefix":"10.64898","author":[{"given":"Mary-Elizabeth","family":"Jobson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brooke R.","family":"Tomlinson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilee M","family":"Mustor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily A","family":"Felton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andy","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3793-8804","authenticated-orcid":false,"given":"Clayton C.","family":"Caswell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0629-8990","authenticated-orcid":false,"given":"Lindsey N.","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025030703550478000_2024.07.11.603084v2.1","doi-asserted-by":"crossref","unstructured":"Carroll RK , Weiss A , Broach WH , Wiemels RE , Mogen AB , Rice KC , Shaw LN . 2016. Genome-wide annotation, identification, and global transcriptomic analysis of regulatory or small RNA gene expression in Staphylococcus aureus . mBio 7.","DOI":"10.1128\/mBio.01990-15"},{"key":"2025030703550478000_2024.07.11.603084v2.2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.00803"},{"key":"2025030703550478000_2024.07.11.603084v2.3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503838102"},{"issue":"4","key":"2025030703550478000_2024.07.11.603084v2.4","first-page":"e00439","article-title":"Reading between the Lines: Utilizing RNA-Seq Data for Global Analysis of sRNAs in Staphylococcus aureus","volume":"5","year":"2020","journal-title":"mSphere"},{"key":"2025030703550478000_2024.07.11.603084v2.5","first-page":"7","article-title":"Transcriptomic analysis of staphylococcal sRNAs: Insights into species-specific adaption and the evolution of pathogenesis","volume":"2","year":"2016","journal-title":"Microb Genomics"},{"key":"2025030703550478000_2024.07.11.603084v2.6","doi-asserted-by":"publisher","DOI":"10.1038\/srep41926"},{"key":"2025030703550478000_2024.07.11.603084v2.7","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23137346"},{"key":"2025030703550478000_2024.07.11.603084v2.8","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.666584"},{"key":"2025030703550478000_2024.07.11.603084v2.9","doi-asserted-by":"crossref","unstructured":"Bastock RA , Marino EC , Wiemels RE , Holzschu DL , Keogh RA , Zapf RL , Murphy ER , Carroll RK . 2021. Staphylococcus aureus Responds to Physiologically Relevant Temperature Changes by Altering Its Global Transcript and Protein Profile. mSphere 6.","DOI":"10.1128\/mSphere.01303-20"},{"key":"2025030703550478000_2024.07.11.603084v2.10","doi-asserted-by":"publisher","DOI":"10.3201\/eid2209.151801"},{"key":"2025030703550478000_2024.07.11.603084v2.11","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.02002-14"},{"key":"2025030703550478000_2024.07.11.603084v2.12","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab782"},{"key":"2025030703550478000_2024.07.11.603084v2.13","doi-asserted-by":"crossref","unstructured":"McKellar SW , Ivanova I , Arede P , Zapf RL , Mercier N , Chu LC , Mediati DG , Pickering AC , Briaud P , Foster RG , Kudla G , Ross Fitzgerald J , Caldelari I , Carroll RK , Tree JJ , Granneman S . 2022. RNase III CLASH in MRSA uncovers sRNA regulatory networks coupling metabolism to toxin expression. 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The Staphylococcus aureus small non-coding RNA IsrR regulates TCA cycle activity and virulence. bioRxiv 2024.07.03.601953.","DOI":"10.1101\/2024.07.03.601953"},{"key":"2025030703550478000_2024.07.11.603084v2.51","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12943"},{"key":"2025030703550478000_2024.07.11.603084v2.52","doi-asserted-by":"publisher","DOI":"10.1086\/598967"},{"key":"2025030703550478000_2024.07.11.603084v2.53","doi-asserted-by":"publisher","DOI":"10.1086\/649570"},{"key":"2025030703550478000_2024.07.11.603084v2.54","first-page":"2037","article-title":"Differential regulation of staphylococcal virulence by the sensor kinase SaeS in response to neutrophil-derived stimuli","volume":"111","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025030703550478000_2024.07.11.603084v2.55","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14404"},{"key":"2025030703550478000_2024.07.11.603084v2.56","first-page":"1","article-title":"The Major Autolysin Atl Regulates the Virulence of Staphylococcus aureus by Controlling the Sorting of LukAB","volume":"90","year":"2022","journal-title":"Infect Immun"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.07.11.603084","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T06:42:08Z","timestamp":1768459328000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.07.11.603084"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,11]]},"references-count":56,"URL":"https:\/\/doi.org\/10.1101\/2024.07.11.603084","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1128\/mbio.00772-25","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2024,7,11]]},"subtype":"preprint"}}