{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T01:45:44Z","timestamp":1789436744502,"version":"build-2803163510"},"reference-count":90,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"vor","delay-in-days":1731,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R33 AI119327"],"award-info":[{"award-number":["R33 AI119327"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI114790"],"award-info":[{"award-number":["R01 AI114790"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01 GM32373"],"award-info":[{"award-number":["R01 GM32373"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Neisseria gonorrhoeae deploys a unique immune evasion strategy wherein the lacto-N-neotetraose termini of lipooligosaccharide (LOS) are \u201ccapped\u201d by a surface LOS sialyltransferase (Lst), using extracellular host-derived CMP-sialic acid (CMP-Neu5Ac in humans). LOS sialylation enhances complement resistance by recruiting factor H (FH; alternative complement pathway inhibitor) and also by limiting classical pathway activation. Sialylated LOS also engages inhibitory Siglecs on host leukocytes, dampening innate immunity. Previously, we showed that analogues of CMP-sialic acids (CMP-nonulosonates [CMP-NulOs]), such as CMP-Leg5,7Ac2 and CMP-Neu5Ac9N3, are also substrates for Lst. Incorporation of Leg5,7Ac2 and Neu5Ac9N3 into LOS results in N. gonorrhoeae being fully serum sensitive. Importantly, intravaginal administration of CMP-Leg5,7Ac2 attenuated N. gonorrhoeae colonization of mouse vaginas. In this study, we characterize and develop additional candidate therapeutic CMP-NulOs. CMP-ketodeoxynonulosonate (CMP-Kdn) and CMP-Kdn7N3, but not CMP-Neu4,5Ac2, were substrates for Lst, further elucidating gonococcal Lst specificity. Lacto-N-neotetraose LOS capped with Kdn and Kdn7N3 bound FH to levels \u223c60% of that seen with Neu5Ac and enabled gonococci to resist low (3.3%) but not higher (10%) concentrations of human complement. CMP-Kdn, CMP-Neu5Ac9N3, and CMP-Leg5,7Ac2 administered intravaginally (10 \u03bcg\/d) to N. gonorrhoeae\u2013colonized mice were equally efficacious. Of the three CMP-NulOs above, CMP-Leg5,7Ac2 was the most pH and temperature stable. In addition, Leg5,7Ac2-fed human cells did not display this NulO on their surface. Moreover, CMP-Leg5,7Ac2 was efficacious against several multidrug-resistant gonococci in mice with a humanized sialome (Cmah\u2212\/\u2212 mice) or humanized complement system (FH\/C4b-binding protein transgenic mice). CMP-Leg5,7Ac2 and CMP-Kdn remain viable leads as topical preventive\/therapeutic agents against the global threat of multidrug-resistant N. gonorrhoeae.<\/jats:p>","DOI":"10.4049\/jimmunol.1901398","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T21:26:44Z","timestamp":1590010004000},"page":"3283-3295","source":"Crossref","is-referenced-by-count":14,"title":["Therapeutic CMP-Nonulosonates against Multidrug-Resistant <i>Neisseria gonorrhoeae<\/i>"],"prefix":"10.1093","volume":"204","author":[{"given":"Sunita","family":"Gulati","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian C","family":"Schoenhofen","sequence":"additional","affiliation":[{"name":"Human Health Therapeutics Research Centre, National Research Council of Canada , Ottawa, Ontario K1A 0R6 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Lindhout-Djukic","sequence":"additional","affiliation":[{"name":"Human Health Therapeutics Research Centre, National Research Council of Canada , Ottawa, Ontario K1A 0R6 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6047-1416","authenticated-orcid":false,"given":"Melissa J","family":"Schur","sequence":"additional","affiliation":[{"name":"Human Health Therapeutics Research Centre, National Research Council of Canada , Ottawa, Ontario K1A 0R6 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinna S","family":"Landig","sequence":"additional","affiliation":[{"name":"Department of Medicine, Glycobiology Research and Training Center, University of California , San Diego, La Jolla, CA 92093"},{"name":"Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California , San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8195-6981","authenticated-orcid":false,"given":"Sudeshna","family":"Saha","sequence":"additional","affiliation":[{"name":"Department of Medicine, Glycobiology Research and Training Center, University of California , San Diego, La Jolla, CA 92093"},{"name":"Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California , San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingquan","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Medicine, Glycobiology Research and Training Center, University of California , San Diego, La Jolla, CA 92093"},{"name":"Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California , San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9469-9083","authenticated-orcid":false,"given":"Lisa A","family":"Lewis","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2237-2898","authenticated-orcid":false,"given":"Bo","family":"Zheng","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2206-975X","authenticated-orcid":false,"given":"Ajit","family":"Varki","sequence":"additional","affiliation":[{"name":"Department of Medicine, Glycobiology Research and Training Center, University of California , San Diego, La Jolla, CA 92093"},{"name":"Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California , San Diego, La Jolla, CA 92093"}],"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, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,6,15]]},"reference":[{"key":"2025030417512158500_r1","doi-asserted-by":"crossref","first-page":"548","DOI":"10.2471\/BLT.18.228486","article-title":"Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016","volume":"97","author":"Rowley","year":"2019","journal-title":"Bull. 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