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The lipopolysaccharide is a virulence factor of this pathogen, although there are gaps in our understanding of its biosynthesis. Here we report on the characterization of\n            <jats:named-content content-type=\"genus-species\">K. pneumoniae<\/jats:named-content>\n            <jats:italic>lpxL<\/jats:italic>\n            , which encodes one of the enzymes responsible for the late secondary acylation of immature lipid A molecules. Analysis of the available\n            <jats:named-content content-type=\"genus-species\">K. pneumoniae<\/jats:named-content>\n            genomes revealed that this pathogen's genome encodes two orthologues of\n            <jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>\n            LpxL. Using genetic methods and mass spectrometry, we demonstrate that LpxL1 catalyzes the addition of laureate and LpxL2 catalyzes the addition of myristate. Both enzymes acylated\n            <jats:named-content content-type=\"genus-species\">E. coli<\/jats:named-content>\n            lipid A, whereas only LpxL2 mediated\n            <jats:named-content content-type=\"genus-species\">K. pneumoniae<\/jats:named-content>\n            lipid A acylation. We show that LpxL1 is negatively regulated by the two-component system PhoPQ. The lipid A produced by the\n            <jats:italic>lpxL2<\/jats:italic>\n            mutant lacked the 2-hydroxymyristate, palmitate, and 4-aminoarabinose decorations found in the lipid A synthesized by the wild type. The lack of 2-hydroxymyristate was expected since LpxO modifies the myristate transferred by LpxL2 to the lipid A. The absence of the other two decorations is most likely caused by the downregulation of\n            <jats:italic>phoPQ<\/jats:italic>\n            and\n            <jats:italic>pmrAB<\/jats:italic>\n            expression. LpxL2-dependent lipid A acylation protects\n            <jats:named-content content-type=\"genus-species\">Klebsiella<\/jats:named-content>\n            from polymyxins, mediates resistance to phagocytosis, limits the activation of inflammatory responses by macrophages, and is required for pathogen survival in the wax moth (\n            <jats:named-content content-type=\"genus-species\">Galleria mellonella<\/jats:named-content>\n            ). Our findings indicate that the LpxL2 contribution to virulence is dependent on LpxO-mediated hydroxylation of the LpxL2-transferred myristate. Our studies suggest that LpxL2 might be a candidate target in the development of anti-\n            <jats:named-content content-type=\"genus-species\">K. pneumoniae<\/jats:named-content>\n            drugs.\n          <\/jats:p>","DOI":"10.1128\/iai.00068-17","type":"journal-article","created":{"date-parts":[[2017,6,27]],"date-time":"2017-06-27T00:20:22Z","timestamp":1498522822000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":49,"title":["Identification and Characterization of Two Klebsiella pneumoniae\n            <i>lpxL<\/i>\n            Lipid A Late Acyltransferases and Their Role in Virulence"],"prefix":"10.1128","volume":"85","author":[{"given":"Grant","family":"Mills","sequence":"first","affiliation":[{"name":"Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Dumigan","sequence":"additional","affiliation":[{"name":"Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Kidd","sequence":"additional","affiliation":[{"name":"Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, United Kingdom"},{"name":"School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia"},{"name":"Child Health Research Centre, The University of Queensland, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Hobley","sequence":"additional","affiliation":[{"name":"Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 A.","family":"Bengoechea","sequence":"additional","affiliation":[{"name":"Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.71.110601.135414"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3047"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.13.4124-4133.2004"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5310.250"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81750-X"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005779200"},{"key":"e_1_3_3_8_2","first-page":"11","article-title":"Antimicrobial peptide resistance mechanisms of human bacterial pathogens","volume":"8","author":"Nizet V","year":"2006","unstructured":"Nizet V . 2006. Antimicrobial peptide resistance mechanisms of human bacterial pathogens. 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