{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:45:57Z","timestamp":1790959557740,"version":"4.1.0"},"reference-count":49,"publisher":"National Academy of Sciences","issue":"38","license":[{"start":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T00:00:00Z","timestamp":1662940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,9,20]]},"abstract":"<jats:p>\n                    Outer membrane porins in Gram-negative bacteria facilitate antibiotic influx. In\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    , modifications in the porin OmpK36 are implicated in increasing resistance to carbapenems. An analysis of large\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    genome collections, encompassing major healthcare-associated clones, revealed the recurrent emergence of a synonymous cytosine-to-thymine transition at position 25 (25c &gt; t) in\n                    <jats:italic>ompK36.<\/jats:italic>\n                    We show that the 25c &gt; t transition increases carbapenem resistance through depletion of OmpK36 from the outer membrane. The mutation attenuates\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    in a murine pneumonia model, which accounts for its limited clonal expansion observed by phylogenetic analysis. However, in the context of carbapenem treatment, the 25c &gt; t transition tips the balance toward treatment failure, thus accounting for its recurrent emergence. Mechanistically, the 25c &gt; t transition mediates an intramolecular messenger RNA (mRNA) interaction between a uracil encoded by 25t and the first adenine within the Shine\u2013Dalgarno sequence. This specific interaction leads to the formation of an RNA stem structure, which obscures the ribosomal binding site thus disrupting translation. While mutations reducing OmpK36 expression via transcriptional silencing are known, we uniquely demonstrate the repeated selection of a synonymous\n                    <jats:italic>ompK36<\/jats:italic>\n                    mutation mediating translational suppression in response to antibiotic pressure.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2203593119","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T15:19:20Z","timestamp":1662995960000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":50,"title":["Recurrent emergence of\n                    <i>Klebsiella pneumoniae<\/i>\n                    carbapenem resistance mediated by an inhibitory\n                    <i>ompK36<\/i>\n                    mRNA secondary structure"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8437-6731","authenticated-orcid":false,"given":"Joshua L. 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Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia Z.","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4004-7244","authenticated-orcid":false,"given":"Wen Wen","family":"Low","sequence":"additional","affiliation":[{"name":"Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London SW7 2AZ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3785-0554","authenticated-orcid":false,"given":"Fabio","family":"Morecchiato","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Giani","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy"},{"name":"Clinical Microbiology and Virology Unit, Careggi University Hospital, Florence 50134, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Maria","family":"Rossolini","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy"},{"name":"Clinical Microbiology and Virology Unit, Careggi University Hospital, Florence 50134, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5727-4721","authenticated-orcid":false,"given":"Konstantinos","family":"Beis","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Imperial College London, London SW7 2AZ, United Kingdom"},{"name":"Rutherford Appleton Laboratory, Research Complex at Harwell, Didcot, Oxfordshire OX11 0FA, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4545-8413","authenticated-orcid":false,"given":"Stephen J.","family":"Brett","sequence":"additional","affiliation":[{"name":"Department of Surgery and Cancer, Section of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, London SW7 2AZ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2285-777X","authenticated-orcid":false,"given":"Abigail","family":"Clements","sequence":"additional","affiliation":[{"name":"Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London SW7 2AZ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Aanensen","sequence":"additional","affiliation":[{"name":"Centre 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