Fatty acids-based compounds as novel prophylaxis or treatment for oropharyngeal Neisseria gonorrhoeae: an in vitro study.

Oropharyngeal gonorrhoea remains a global challenge due to rising antimicrobial resistance and limited therapeutic options, necessitating urgent calls for new treatments and prophylaxis. This study evaluates the in vitro activity of arginine-based fatty acids against Neisseria gonorrhoeae (NG) strains in a validated oropharyngeal model. Five oropharyngeal cell lines (tonsillar/buccal/gingival/floor of mouth/uvular) were infected with two NG strains. Intracellular infection was assessed at 15/30/60 min. MIC₉₀ and cytotoxicity of five arginine-based fatty acids were determined. Promising candidates were evaluated for NG clearance at 30/60/120 min (post-infection) and prevention of infection (pre-infection) after 30/120 min drug exposure. Arginine-undecanoate (AU) and arginine-laurate (AL) were the most effective fatty-acids, showing potent bactericidal activity, with no cytotoxicity in any cell lines up to 300 µg/mL. In post-exposure experiments, AL at 150 µg/mL and at MICx3 achieved rapid, dose-dependent clearance of ≥94% for FA1090 and ≥90% for WHO R respectively within 30 min in all cell lines except in uvular cells. AU showed time-dependent killing with clearance of ≥95% for FA1090 and ≥88% for WHO-R at 120 min at 150 and 108 µg/mL (MICx3) respectively. In pre-exposure experiments, AL at maximum non-cytotoxic concentration (300 µg/mL) was more effective than AU, achieving 83·3-97·4% clearance in all cell lines within 30 min. AL and AU can be promising, non-toxic candidates for the prevention or treatment of oropharyngeal NG. Use, pre- and post-sex via topical formulations, could potentially reduce oropharyngeal NG transmission.