{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:16:11Z","timestamp":1791944171008,"version":"4.3.4"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Hypervirulent\n                      <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                      (hvKP) is an emerging pathogen associated with severe invasive infections and high mortality, in which resistance to host-derived reactive oxygen species (ROS) is critical for immune evasion and persistence. However, the mechanisms underlying oxidative stress resistance in hvKP remain poorly understood, and the role of the global regulator OxyR in this species has not been fully elucidated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, VK055_RS16305 was first identified as an OxyR homologue in\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      ATCC 43816 by sequence alignment. The\n                      <jats:italic>oxyR<\/jats:italic>\n                      deletion mutant was generated using a CRISPR\/Cas9-based genome editing system, whereas the complemented strain was obtained using the pSTV28 plasmid carrying\n                      <jats:italic>oxyR<\/jats:italic>\n                      . We then compared their growth characteristics, susceptibility to H\u2082O\u2082, biofilm formation, and virulence in\n                      <jats:italic>Galleria mellonella<\/jats:italic>\n                      and mouse infection models, and performed RNA sequencing followed by qRT-PCR to characterize the OxyR regulon under oxidative stress.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Deletion of\n                      <jats:italic>oxyR<\/jats:italic>\n                      did not alter bacterial growth or colony morphology under non-stress conditions, but markedly increased susceptibility to H\u2082O\u2082 and impaired biofilm formation.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , the\n                      <jats:italic>oxyR<\/jats:italic>\n                      mutant exhibited attenuated virulence, with improved survival of\n                      <jats:italic>Galleria mellonella<\/jats:italic>\n                      and mice and significantly reduced bacterial burdens in blood, liver, lung, and spleen, all of which were restored by genetic complementation. Transcriptomic analysis revealed that OxyR positively regulates multiple oxidative stress\u2013associated genes, including\n                      <jats:italic>hemH, grxA, gsk, katG<\/jats:italic>\n                      , and\n                      <jats:italic>ahpC<\/jats:italic>\n                      , in response to H\u2082O\u2082.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Together, these findings demonstrate that OxyR is a key regulator of oxidative stress defense, biofilm formation, and systemic virulence in hvKP, providing new insight into OxyR-mediated pathogenic mechanisms in\n                      <jats:italic>K. pneumoniae<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1661384","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T06:53:31Z","timestamp":1767768811000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["OxyR contributes to the oxidative stress capacity and virulence of hypervirulent Klebsiella pneumoniae ATCC 43816"],"prefix":"10.3389","volume":"15","author":[{"given":"Ruxia","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanqiu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojue","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1093\/molbev\/msz251","article-title":"OxyR is a convergent target for mutations acquired during adaptation to oxidative stress-prone metabolic states","volume":"37","author":"Anand","year":"2020","journal-title":"Mol. 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