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N.\u2002gonorrhoeae LOS sialylation blocks killing by complement, which is mediated at least in part by enhanced binding of the complement inhibitor factor H (FH). The role of LOS sialylation in resistance of N.\u2002meningitidis to serum killing is less well defined. Sialylation in each species is catalyzed by the enzyme LOS \u03b1-2,3-sialyltransferase (Lst). Previous studies have shown increased Lst activity in N.\u2002gonorrhoeae compared to N.\u2002meningitidis due to an ~5-fold increase in\n                    <jats:italic>lst<\/jats:italic>\n                    transcription. Using isogenic N.\u2002gonorrhoeae strains engineered to express gonococcal\n                    <jats:italic>lst<\/jats:italic>\n                    from either the N.\u2002gonorrhoeae or N.\u2002meningitidis\n                    <jats:italic>lst<\/jats:italic>\n                    promoter, we show that decreased expression of\n                    <jats:italic>lst<\/jats:italic>\n                    (driven by the N.\u2002meningitidis promoter) reduced LOS sialylation as determined by less incorporation of tritium-labeled cytidine monophospho-\n                    <jats:italic>N<\/jats:italic>\n                    -acetylneuraminic acid (CMP-NANA; the donor molecule for sialic acid). Diminished LOS sialylation resulted in reduced rates of FH binding and increased pathway activation compared to N.\u2002gonorrhoeae promoter-driven\n                    <jats:italic>lst<\/jats:italic>\n                    expression. The N.\u2002meningitidis\n                    <jats:italic>lst<\/jats:italic>\n                    promoter generated sufficient Lst to sialylate N.\u2002gonorrhoeae LOS\n                    <jats:italic>in vivo<\/jats:italic>\n                    , and the level of sialylation after 24\u00a0h in the mouse genital tract was sufficient to mediate resistance to human serum\n                    <jats:italic>ex vivo<\/jats:italic>\n                    . Despite demonstrable LOS sialylation\n                    <jats:italic>in vivo<\/jats:italic>\n                    , gonococci harboring the N.\u2002meningitidis\n                    <jats:italic>lst<\/jats:italic>\n                    promoter were outcompeted by those with the N.\u2002gonorrhoeae\n                    <jats:italic>lst<\/jats:italic>\n                    promoter during coinfection of the vaginal tract of estradiol-treated mice. These data highlight the importance of high\n                    <jats:italic>lst<\/jats:italic>\n                    expression levels for gonococcal pathogenesis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    \u2002\n                    <jats:named-content content-type=\"genus-species\">Neisseria gonorrhoeae<\/jats:named-content>\n                    has become resistant to nearly every therapeutic antibiotic used and is listed as an \u201curgent threat\u201d by the Centers for Disease Control and Prevention. Novel therapies are needed to combat drug-resistant N.\u2002gonorrhoeae. Gonococci express an \u03b1-2,3-sialyltransferase (Lst) that can scavenge sialic acid from the host and use it to modify lipooligosaccharide (LOS). Sialylation of gonococcal LOS converts serum-sensitive strains to serum resistance, decreases antibody binding, and combats killing by neutrophils and antimicrobial peptides. Mutant N.\u2002gonorrhoeae that lack Lst (cannot sialylate LOS) are attenuated in a mouse model. Lst expression levels differ among N.\u2002gonorrhoeae strains, and N.\u2002gonorrhoeae typically expresses more Lst than\n                    <jats:named-content content-type=\"genus-species\">Neisseria meningitidis<\/jats:named-content>\n                    . Here we examined the significance of differential\n                    <jats:italic>lst<\/jats:italic>\n                    expression levels and determined that the level of LOS sialylation is critical to the ability of N.\u2002gonorrhoeae to combat the immune system and survive in an animal model. LOS sialylation may be an ideal target for novel therapies.\n                  <\/jats:p>","DOI":"10.1128\/mbio.02465-14","type":"journal-article","created":{"date-parts":[[2015,2,3]],"date-time":"2015-02-03T22:51:18Z","timestamp":1423003878000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":41,"title":["\u03b1-2,3-Sialyltransferase Expression Level Impacts the Kinetics of Lipooligosaccharide Sialylation, Complement Resistance, and the Ability of Neisseria gonorrhoeae to Colonize the Murine Genital Tract"],"prefix":"10.1128","volume":"6","author":[{"given":"Lisa A.","family":"Lewis","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunita","family":"Gulati","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Burrowes","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zheng","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Ram","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Rice","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"crossref","unstructured":"Joiner KA Warren KA Brown EJ Swanson J Frank MM. 1983. 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