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Several viral infections have been shown to alter vascular biology, but effects of bacterial pathogens are unclear. Here using an ex vivo blood vessel model and human primary endothelial cells, we show that\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    , a prevalent bloodstream pathogen, inhibits vasodilation pathways. The type\u2009VI secretion system (T6SS) effector VgrG4 activates the mitochondrial receptor NLRX1, which leads to increased mitochondrial reactive oxygen species and phosphorylation of the eNOS inhibitory site by the kinase PKC\u03b2, which in turn reduces eNOS activity.\n                    <jats:italic>K.<\/jats:italic>\n                    \u2009\n                    <jats:italic>pneumoniae<\/jats:italic>\n                    capsule polysaccharide also activates the phosphatase PP2Ac, which reduces phosphorylation of the eNOS activation site. VgrG4-induced mitochondrial reactive oxygen species attenuate endothelium-dependent hyperpolarization by impairing signalling of the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -activated K\n                    <jats:sup>+<\/jats:sup>\n                    channel axis. This work reveals that T6SS activity can modulate host vascular biology by targeting eNOS post-translational modifications.\n                  <\/jats:p>","DOI":"10.1038\/s41564-026-02425-0","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T09:03:13Z","timestamp":1784624593000},"page":"2170-2186","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Klebsiella pneumoniae inhibits vasodilation through capsule and T6SS-dependent pathways"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2960-4305","authenticated-orcid":false,"given":"Safi","family":"Rehman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0038-2120","authenticated-orcid":false,"given":"Joana","family":"Sa-Pessoa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7961-4544","authenticated-orcid":false,"given":"Charlotte","family":"Buckley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0731-8473","authenticated-orcid":false,"given":"Rachel L.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Wojtania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0074-4348","authenticated-orcid":false,"given":"Alix","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Lancaster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josy","family":"Augustine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Barabas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciara","family":"Ross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0790-4291","authenticated-orcid":false,"given":"Xun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3302-3984","authenticated-orcid":false,"given":"John G.","family":"McCarron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1543-2781","authenticated-orcid":false,"given":"Tim M.","family":"Curtis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9677-8751","authenticated-orcid":false,"given":"Jose A.","family":"Bengoechea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"2425_CR1","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.1097\/01.ASN.0000132474.50966.DA","volume":"15","author":"DH Endemann","year":"2004","unstructured":"Endemann, D. 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