{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:58:42Z","timestamp":1785427122818,"version":"3.56.0"},"reference-count":28,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Major Research and Development Project of Lishui City","award":["2023ZDYF16"],"award-info":[{"award-number":["2023ZDYF16"]}]},{"DOI":"10.13039\/100017054","name":"NSFC-Zhejiang Joint Fund","doi-asserted-by":"publisher","award":["LHDMY24H190001"],"award-info":[{"award-number":["LHDMY24H190001"]}],"id":[{"id":"10.13039\/100017054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017054","name":"NSFC-Zhejiang Joint Fund","doi-asserted-by":"publisher","award":["LHDMZ23H190001"],"award-info":[{"award-number":["LHDMZ23H190001"]}],"id":[{"id":"10.13039\/100017054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2025YFE0206100"],"award-info":[{"award-number":["2025YFE0206100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,6,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Gly115-Asp116 (GD) insertion in the outer membrane porin OmpK36 is prevalent in carbapenem-resistant, KPC-producing\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      , but the molecular mechanisms linking this mutation to enhanced resistance cannot be explained simply by reduced drug permeability. Given that porin mutations compromise bacterial fitness, we investigated the potential role of the stress response regulator RpoS in OmpK36-mediated carbapenemase regulation. Our results demonstrated that among 127 clinical isolates, OmpK36 GD insertion occurred in 50.4% of isolates and was associated with a significantly elevated carbapenem minimum inhibitory concentration and enhanced high-level resistance. In genetically modified strains, the OmpK36 GD insertion impaired bacterial growth and led to a 3.7-fold upregulated\n                      <jats:italic toggle=\"yes\">rpoS<\/jats:italic>\n                      expression and a 2.7-fold increase in\n                      <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                      <jats:sub>KPC-2<\/jats:sub>\n                      expression. Bioinformatics analysis identified a putative RpoS binding site in the\n                      <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                      <jats:sub>KPC<\/jats:sub>\n                      promoter region, which was validated by electrophoretic mobility shift assays. Moreover, RpoS overexpression enhanced\n                      <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                      <jats:sub>KPC-2<\/jats:sub>\n                      expression 1.7-fold and increased carbapenem resistance, while disruption of the RpoS binding site reduced\n                      <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                      <jats:sub>KPC-2<\/jats:sub>\n                      expression fourfold and decreased resistance levels. Subinhibitory antibiotic treatment upregulated both\n                      <jats:italic toggle=\"yes\">rpoS<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                      <jats:sub>KPC-2<\/jats:sub>\n                      expression across multiple strains, further validating a RpoS-mediated regulatory mechanism. These results suggest that OmpK36 GD insertion contributes to carbapenem resistance through RpoS-mediated transcriptional upregulation of\n                      <jats:italic toggle=\"yes\">bla<\/jats:italic>\n                      <jats:sub>KPC<\/jats:sub>\n                      , revealing a stress-activated regulatory mechanism linking porin structural alterations to modulated carbapenemase expression in\n                      <jats:italic toggle=\"yes\">K. pneumoniae<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01824-25","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T10:00:21Z","timestamp":1776679221000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["OmpK36 GD insertion induces RpoS-dependent\n                    <i>bla<\/i>\n                    <sub>KPC<\/sub>\n                    overexpression in carbapenem-resistant\n                    <i>Klebsiella pneumoniae<\/i>"],"prefix":"10.1128","volume":"70","author":[{"given":"Jinnuo","family":"Zhu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04epb4p87","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Laboratory, Graduate Joint Training Base of Zhejiang Chinese Medical University (Lishui Joint Training Base, Lishui Central Hospital)","place":["Lishui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhen","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04epb4p87","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Clinical Laboratory, Graduate Joint Training Base of Zhejiang Chinese Medical University (Lishui Joint Training Base, Lishui Central Hospital)","place":["Lishui, 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