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However, a molecular understanding of their lifestyle changes within the human host is lacking. Here, by directly examining bacterial gene expression in human-derived samples, we discover a gene that orchestrates the transition between chronic and acute infection in the opportunistic pathogen\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    . The expression level of this gene, here named\n                    <jats:italic>sicX<\/jats:italic>\n                    , is the highest of the\n                    <jats:italic>P.<\/jats:italic>\n                    \u2009\n                    <jats:italic>aeruginosa<\/jats:italic>\n                    genes expressed in human chronic wound and cystic fibrosis infections, but it is expressed at extremely low levels during standard laboratory growth. We show that\n                    <jats:italic>sicX<\/jats:italic>\n                    encodes a small RNA that is strongly induced by low-oxygen conditions and post-transcriptionally regulates anaerobic ubiquinone biosynthesis. Deletion of\n                    <jats:italic>sicX<\/jats:italic>\n                    causes\n                    <jats:italic>P.<\/jats:italic>\n                    \u2009\n                    <jats:italic>aeruginosa<\/jats:italic>\n                    to switch from a chronic to an acute lifestyle in multiple mammalian models of infection. Notably,\n                    <jats:italic>sicX<\/jats:italic>\n                    is also a biomarker for this chronic-to-acute transition, as it is the most downregulated gene when a chronic infection is dispersed to cause acute septicaemia. This work solves a decades-old question regarding the molecular basis underlying the chronic-to-acute switch in\n                    <jats:italic>P.<\/jats:italic>\n                    \u2009\n                    <jats:italic>aeruginosa<\/jats:italic>\n                    and suggests oxygen as a primary environmental driver of acute lethality.\n                  <\/jats:p>","DOI":"10.1038\/s41586-023-06111-7","type":"journal-article","created":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T12:02:31Z","timestamp":1684929751000},"page":"358-364","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":116,"title":["A Pseudomonas aeruginosa small RNA regulates chronic and acute infection"],"prefix":"10.1038","volume":"618","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6599-8121","authenticated-orcid":false,"given":"Pengbo","family":"Cao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Fleming","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9616-5947","authenticated-orcid":false,"given":"Dina A.","family":"Moustafa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen K.","family":"Dolan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla H.","family":"Szymanik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Whitni K.","family":"Redman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2275-0956","authenticated-orcid":false,"given":"Anayancy","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances L.","family":"Diggle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher S.","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna B.","family":"Goldberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendra P.","family":"Rumbaugh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6590-4703","authenticated-orcid":false,"given":"Marvin","family":"Whiteley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,5,24]]},"reference":[{"key":"6111_CR1","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/s41579-020-00477-5","volume":"19","author":"E Rossi","year":"2021","unstructured":"Rossi, E. et al. 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