{"doi":"10.1093/infdis/jiaa438","title":"Efficacy of Antigonococcal CMP-Nonulosonate Therapeutics Require Cathelicidins","abstract":"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.","journal":"The Journal of Infectious Diseases","year":2020,"id":78107,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9537,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":408017,"name":"Ian C. Schoenhofen","orcid":null,"position":1,"is_corresponding":false},{"id":406673,"name":"Theresa Lindhout","orcid":"0000-0003-4745-6913","position":2,"is_corresponding":false},{"id":406674,"name":"Lisa A. Lewis","orcid":"0000-0001-9469-9083","position":3,"is_corresponding":false},{"id":408018,"name":"Iesha Y Moustafa","orcid":null,"position":4,"is_corresponding":false},{"id":406675,"name":"Sudeshna Saha","orcid":"0000-0002-8195-6981","position":5,"is_corresponding":false},{"id":406676,"name":"Bo Zheng","orcid":"0000-0002-2237-2898","position":6,"is_corresponding":false},{"id":408019,"name":"Nancy Nowak","orcid":null,"position":7,"is_corresponding":false},{"id":408020,"name":"Peter A. Rice","orcid":null,"position":8,"is_corresponding":false},{"id":313878,"name":"Ajit Varki","orcid":"0000-0002-2206-975X","position":9,"is_corresponding":false},{"id":406677,"name":"Sanjay Ram","orcid":"0000-0003-0058-9532","position":10,"is_corresponding":false},{"id":408016,"name":"Sunita Gulati","orcid":null,"position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-18T21:49:40.769098Z","pmid":"32692363","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}