Antimicrobial effects of Medicines for Malaria Venture Pathogen Box compounds on strains of Neisseria gonorrhoeae

• Published in: Antimicrobial agents and chemotherapy 2023-11, Vol.67 (11), p.e0034823-e0034823
• Main Authors: Mensah, Eric, Fourie, P Bernard, Peters, Remco P H
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Anti-Infective Agents - pharmacology; Ceftriaxone - pharmacology; Gonorrhea - drug therapy; Humans; Microbial Sensitivity Tests; Neisseria gonorrhoeae
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/aac.00348-23

Therapeutic options for are limited due to emerging global resistance. New agents and treatment options to treat patients with susceptible and multi-extensively drug-resistant is a high priority. This study used an approach to explore the antimicrobial potential, as well as synergistic effects of Medicine for Malaria Venture (MMV) Pathogen Box compounds against ATCC and clinical strains. Microbroth dilution assay was used to determine pathogen-specific minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the Pathogen Box compounds against susceptible and resistant strains, with modification, by adding PrestoBlue HS Cell Viability Reagent. A checkerboard assay was used to determine synergy between the active compounds and in conjunction with ceftriaxone. Time-kill kinetics was performed to determine if the compounds were either bactericidal or bacteriostatic. The Pathogen Box compounds: MMV676501, MMV002817, MMV688327, MMV688508, MMV024937, MMV687798 (levofloxacin), MMV021013, and MMV688978 (auranofin) showed potent activity against resistant strains of at an MIC and MBC of ≤10 µM. Besides the eight compounds, MMV676388 and MMV272144 were active against susceptible strains, also at MIC and MBC of ≤10 µM. All the compounds were bactericidal and were either synergistic or additive with fractional inhibitory concentration index ranging between 0.40 and 1.8. The study identified novel Pathogen Box compounds with potent activity against strains and has the potential to be further investigated as primary or adjunctive therapy to treat gonococcal infections.