Repurposing the Natural Product Maslinic Acid for Combating Clostridioides difficile Infections
- 1Department of Biomedical Sciences and Pathobiology Virginia-Maryland College of Veterinary Medicine Virginia Polytechnic Institute and State University Blacksburg Virginia USA vt.edu
- 2Center for One Health Research Virginia Polytechnic Institute and State University Blacksburg Virginia USA vt.edu
- 3Department of Microbiology and Immunology Faculty of Pharmacy Zagazig University Zagazig Al-Sharqia Egypt zu.edu.eg
Abstract
Clostridioides difficile infection remains a leading cause of healthcare‐associated diarrhea, and treatment options remain constrained by frequent recurrence and disruption of the intestinal microbiota. Natural products with selective antibacterial activity may provide new therapeutic opportunities for C. difficile. In this study, the pentacyclic triterpene maslinic acid, a naturally occurring compound abundant in olives and olive‐derived products, was evaluated for its antibacterial activity against C. difficile. Maslinic acid inhibited a diverse panel of clinical isolates, including hypervirulent strains, with MIC values of 8–16 μg/mL while exhibiting substantially weaker activity against representative commensal gut bacteria. Time‐kill studies demonstrated complete elimination of detectable C. difficile within 2 h of treatment, indicating rapid bactericidal activity. Additionally, its antibacterial potency was preserved when tested at high bacterial inoculum and following prolonged exposure to simulated gastric and intestinal fluids, suggesting favorable stability under gastrointestinal conditions. Maslinic acid also showed no cytotoxicity to Caco‐2 cells at concentrations substantially exceeding its MICs. Mechanistic studies further indicated that maslinic acid preferentially interfered with protein and lipid biosynthetic pathways without evidence of membrane disruption. Moreover, evaluation of structurally related pentacyclic triterpenes identified several analogs with comparable activity with maslinic acid and highlighted structural features associated with antibacterial potency. Collectively, these findings identify maslinic acid as a selective, rapidly bactericidal natural product with characteristics that support its continued investigation as a potential therapeutic candidate for C. difficile infections.
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BibTeX
@article{stolz2026repurposing,
title = {{Repurposing the Natural Product Maslinic Acid for Combating Clostridioides difficile Infections}},
author = {Brice J. Stolz and Nader S. Abutaleb and Ahmed A. Abouelkhair and Mohamed N. Seleem},
journal = {International Journal of Microbiology},
year = {2026},
month = nov,
doi = {10.1155/ijm/9364932},
url = {https://doi.org/10.1155/ijm/9364932},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Repurposing the Natural Product Maslinic Acid for Combating Clostridioides difficile Infections
AU - Brice J. Stolz
AU - Nader S. Abutaleb
AU - Ahmed A. Abouelkhair
AU - Mohamed N. Seleem
PY - 2026
DA - 2026/11/02
JO - International Journal of Microbiology
DO - 10.1155/ijm/9364932
UR - https://doi.org/10.1155/ijm/9364932
AB - Clostridioides difficile infection remains a leading cause of healthcare‐associated diarrhea, and treatment options remain constrained by frequent recurrence and disruption of the intestinal microbiota. Natural products with selective antibacterial activity may provide new therapeutic opportunities for C. difficile. In this study, the pentacyclic triterpene maslinic acid, a naturally occurring compound abundant in olives and olive‐derived products, was evaluated for its antibacterial activity against C. difficile. Maslinic acid inhibited a diverse panel of clinical isolates, including hypervirulent strains, with MIC values of 8–16 μg/mL while exhibiting substantially weaker activity against representative commensal gut bacteria. Time‐kill studies demonstrated complete elimination of detectable C. difficile within 2 h of treatment, indicating rapid bactericidal activity. Additionally, its antibacterial potency was preserved when tested at high bacterial inoculum and following prolonged exposure to simulated gastric and intestinal fluids, suggesting favorable stability under gastrointestinal conditions. Maslinic acid also showed no cytotoxicity to Caco‐2 cells at concentrations substantially exceeding its MICs. Mechanistic studies further indicated that maslinic acid preferentially interfered with protein and lipid biosynthetic pathways without evidence of membrane disruption. Moreover, evaluation of structurally related pentacyclic triterpenes identified several analogs with comparable activity with maslinic acid and highlighted structural features associated with antibacterial potency. Collectively, these findings identify maslinic acid as a selective, rapidly bactericidal natural product with characteristics that support its continued investigation as a potential therapeutic candidate for C. difficile infections.
SN - 1687-918X
SN - 1687-9198
ER -