{"id":13415,"date":"2025-09-18T14:55:00","date_gmt":"2025-09-18T14:55:00","guid":{"rendered":"https:\/\/www.sygnaturediscovery.com\/?post_type=journal-paper&p=13415"},"modified":"2026-01-29T15:23:55","modified_gmt":"2026-01-29T15:23:55","slug":"the-bactericidal-fabi-inhibitor-debio-1453-clears-antibiotic-resistant-neisseria-gonorrhoeae-infection-in-vivo","status":"publish","type":"journal-paper","link":"https:\/\/www.sygnaturediscovery.com\/fr\/journal-paper\/the-bactericidal-fabi-inhibitor-debio-1453-clears-antibiotic-resistant-neisseria-gonorrhoeae-infection-in-vivo\/","title":{"rendered":"The bactericidal FabI inhibitor Debio 1453 clears antibiotic-resistant\u00a0Neisseria gonorrhoeae\u00a0infection in vivo"},"content":{"rendered":"\n

Vincent Gerusz,\u00a0Pierre Regenass,\u00a0Quentin Rousseau,\u00a0Victor Moraine,\u00a0Justine Dao,\u00a0Xavier Lav\u00e9,\u00a0Shampa Das,\u00a0Jos\u00e9e Hue Perron,\u00a0Laurence Fajas Descamps,\u00a0Juan Bravo,\u00a0Guenna\u00eblle Dieppois,\u00a0Nachum Kaplan,\u00a0Matthew Lefebre,\u00a0Deanna Altomari,\u00a0Vladimir Romanov,\u00a0Terry Finn,\u00a0Pierre Daram,\u00a0Francesca Bernardini,\u00a0Micha\u00ebl Gross,\u00a0Robert Lysek,\u00a0Aur\u00e9lien Adam,\u00a0Danig Pohin,\u00a0Maurizio Maio,\u00a0Vasileios Tatsis<\/strong>,\u00a0Mihiro Sunose<\/strong>,\u00a0C\u00e9line Ronin, Fabrice Ciesielski,\u00a0Josefine Ahlstrand,\u00a0Susanne Jacobsson,\u00a0Magnus Unemo\u00a0&\u00a0David R. Cameron\u00a0<\/p>\n\n\n\n

Abstract<\/strong><\/p>\n\n\n\n

Gonorrhoea is a prevalent sexually transmitted infection caused by the bacterial pathogen Neisseria gonorrhoeae<\/em>. N. gonorrhoeae<\/em> has demonstrated a remarkable capacity to evolve antibiotic resistance, with emerging strains that show resistance to all standard treatment options. The development of new antibiotics for gonorrhoea, especially those with novel targets and no pre-existing resistance, is critical. One such untapped antibacterial target in N. gonorrhoeae<\/em> is FabI, an enoyl-acyl carrier protein reductase enzyme that is essential for fatty acid biosynthesis in this pathogen. In the current report, structure-based drug design using novel N. gonorrhoeae<\/em> FabI inhibitor co-crystals guides medicinal chemistry toward increasing potency in the sub-nanomolar range and drives the discovery of Debio 1453. Debio 1453 is optimized for activity against N. gonorrhoeae<\/em> and is highly active in vitro against diverse N. gonorrhoeae<\/em> isolates including those resistant to the last remaining treatment options. Additionally, the compound presents a low propensity for selection of mutants with reduced susceptibility. Debio 1453 is efficacious in vivo against N. gonorrhoeae<\/em> isolates with clinically relevant multi-drug resistance phenotypes in a murine vaginal gonorrhoea infection model underscoring Debio 1453 as a promising candidate for the treatment of gonorrhoea.<\/p>\n\n\n\n

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