The fungal natural product fusidic acid demonstrates potent activity against Mycoplasma genitalium

• Published in: Antimicrobial agents and chemotherapy Vol. 68; no. 10; p. e0100624
• Main Authors: Wood, Gwendolyn E, Lee, Jin Woo, Peramuna, Thilini, Wendt, Karen L, Kim, Caroline M, Aguila, Laarni Kendra T, Calderon, Claire L, Cichewicz, Robert H
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 29.08.2024
• Subjects: Antimicrobial Chemotherapy; Susceptibility; fungal natural products; Mycoplasma genitalium; antimicrobial resistance; fusidic acid
• ISSN: 0066-4804; 1098-6596; 1098-6596
• DOI: 10.1128/aac.01006-24

Antimicrobial resistance is extremely common in , a frequent cause of urethritis in men and cervicitis, vaginitis, and pelvic inflammatory disease in women. Treatment of infections is difficult due to intrinsic and acquired resistance to many antibiotic classes. We undertook a program to identify novel antimicrobials with activity against from fungal natural products. Extracts of contained a molecule with potent activity that was subsequently identified as fusidic acid, a fusidane-type antibiotic that has been in clinical use for decades outside the United States. We found that minimum inhibitory concentrations of fusidic acid ranged from 0.31 to 4 µg/mL among 17 . strains including laboratory-passaged and low-passage clinical isolates. Time-kill data indicate that bactericidal killing occurs when is exposed to ≥10 µg/mL for 48 h, comparing favorably to serum concentrations obtained from typical loading dose regimens. Resistance to fusidic acid was associated with mutations in consistent with the known mechanism of action in which fusidic acid inhibits protein synthesis by binding to elongation factor G. Interestingly, no mutants resistant to >10 µg/mL fusidic acid were obtained and a resistant strain containing a F435Y mutation in FusA was impaired for growth . These data suggest that fusidic acid may be a promising option for the treatment of infections.