{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T08:38:01Z","timestamp":1789029481018,"version":"build-2803163510"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"10","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R33 AI119327"],"award-info":[{"award-number":["R33 AI119327"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI114790"],"award-info":[{"award-number":["R01 AI114790"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 GM32373"],"award-info":[{"award-number":["R01 GM32373"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,13]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Novel therapies to counteract multidrug-resistant gonorrhea are urgently needed. A unique gonococcal immune evasion strategy involves capping of lipooligosaccharide (LOS) with sialic acid by gonococcal sialyltransferase (Lst), utilizing host-derived CMP-sialic acid (CMP-Neu5Ac in humans). LOS sialylation renders gonococci resistant to complement and cationic peptides, and down-regulates the inflammatory response by engaging siglecs. CMP-sialic acid analogs (CMP-nonulosonates [CMP-NulOs]) such as CMP-Leg5,7Ac2 and CMP-Kdn are also utilized by Lst. Incorporation of these NulO analogs into LOS maintains gonococci susceptible to complement. Intravaginal administration of CMP-Kdn or CMP-Leg5,7Ac2 attenuates gonococcal colonization of mouse vaginas. Here, we identify a key mechanism of action for the efficacy of CMP-NulOs. Surprisingly, CMP-NulOs remained effective in complement C1q-\/- and C3-\/- mice. LOS Neu5Ac, but not Leg5,7Ac2 or Kdn, conferred resistance to the cathelicidins LL-37 (human) and mouse cathelicidin-related antimicrobial peptide in vitro. CMP-NulOs were ineffective in Camp-\/- mice, revealing that cathelicidins largely mediate the efficacy of therapeutic CMP-NulOs.<\/jats:p>","DOI":"10.1093\/infdis\/jiaa438","type":"journal-article","created":{"date-parts":[[2020,7,15]],"date-time":"2020-07-15T19:10:21Z","timestamp":1594840221000},"page":"1641-1650","source":"Crossref","is-referenced-by-count":17,"title":["Efficacy of Antigonococcal CMP-Nonulosonate Therapeutics Require Cathelicidins"],"prefix":"10.1093","volume":"222","author":[{"given":"Sunita","family":"Gulati","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"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, 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