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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:p>\n                    <jats:italic toggle=\"yes\">\n                      <jats:italic toggle=\"yes\">Neisseria<\/jats:italic>\n                      gonorrhoeae\n                    <\/jats:italic>\n                    is the causative agent of gonorrhea, a sexually transmitted infection which is rising in incidence, with increasing drug-resistant strains posing a significant public health threat. To address the urgent need for novel therapies, we developed an antibody\u2013drug conjugate (ADC) that targets this important human pathogen. We utilized Tridecaptin A\n                    <jats:sub>1,<\/jats:sub>\n                    a potent antimicrobial peptide (AMP) against Gram-negative bacteria that exhibits significant toxicity against human cells, limiting its development for clinical use. By conjugating the Tridecaptin A\n                    <jats:sub>1<\/jats:sub>\n                    analogue, Oct-TriA\n                    <jats:sub>1<\/jats:sub>\n                    to a monoclonal antibody (mAb) that specifically targets gonococcal MtrE, the outer membrane component of a drug efflux pump that is upregulated in resistant strains, we aim to selectively deliver the AMP to the gonococcus. However, Oct-TriA\n                    <jats:sub>1<\/jats:sub>\n                    was not bactericidal when directly conjugated to mAb. To circumvent this, we exploited an immune evasion mechanism employed by the gonococcus by introducing a linker between Oct-TriA\n                    <jats:sub>1<\/jats:sub>\n                    and the mAb which is specifically cleaved by the IgA protease (IgAP) secreted by the gonococcus; the IgAP inactivates human IgA. This ADC has no detectable toxicity for relevant human cells, kills the gonococcus in an MtrE- and IgAP-dependent manner, and is active against a strain which is resistant to first line agents. This modular ADC platform could be extended to other bacterial pathogens which employ proteases to evade immune killing, offering a strategy in the fight against antimicrobial resistance.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2534217123","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T17:53:14Z","timestamp":1785261194000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["An antibody\u2013drug conjugate active against antibiotic-resistant\n                    <i>\n                      <i>Neisseria<\/i>\n                      gonorrhoeae\n                    <\/i>"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9996-8107","authenticated-orcid":false,"given":"Hayley","family":"Lavender","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Sir William Dunn School of Pathology, University of Oxford","place":["Oxford, United Kingdom"]},{"id":[{"id":"https:\/\/ror.org\/04xs57h96","id-type":"ROR","asserted-by":"publisher"}],"name":"The Department of Clinical Infection, Microbiology, and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool","place":["Liverpool, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3862-9716","authenticated-orcid":false,"given":"Vincent","family":"Oliver","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04q9tew83","id-type":"ROR","asserted-by":"publisher"}],"name":"Henry M. 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