Targeting ESKAPE pathogens with anti-infective medicinal plants from the Greater Mpigi region in Uganda

• Type of Material: Article
• Authors: Fabien Schultz, Emory University; Godwin Anywar, Makerere University; Huaqiao Tang, Emory University; Francois Chassagne, Emory University; James T. Lyles, Emory University; Leif-Alexander Garbe, Technical University of Berlin; Cassandra Quave, Emory University
• Language: English
• Date: 2020-07-20
• Publisher: Nature Research
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2020.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41598-020-67572-8
• Title of Journal or Parent Work: Scientific Reports
• Volume: 10
• Issue: 1
• Start Page: 11935
• End Page: 11935
• Grant/Funding Information: We acknowledge support for the Article Processing Charge from the German Research Foundation (DFG, 414051096) and the Open Access Publication Fund of Neubrandenburg University of Applied Sciences (HSNB).; This work was supported by a Fulbright Fellowship (FS), a Grant from the BMBF—German Federal Ministry of Education and Research (13FH026IX5, PI: LAG and Co-I: FS), and a Grant from the National Institutes of Health, National Institute of Allergy and Infectious Disease (R21 AI13656s3, PI: CQ).
• Keywords: Antibiotic resistance; Staphylococcus aureus; Management; Science & Technology - Other Topics; Traditional herbal drugs; Enterococcus faecium; Antimicrobial activity; Multidisciplinary Sciences; Science & Technology; Solanum-aculeastrum; Delta toxin; Virulence
• Research Categories: Agriculture, Food Science and Technology; Health Sciences, Public Health; Biology, Microbiology; Engineering, Biomedical

Abstract

Antibiotic resistance poses one of the greatest threats to global health today; conventional drug therapies are becoming increasingly inefficacious and limited. We identified 16 medicinal plant species used by traditional healers for the treatment of infectious and inflammatory diseases in the Greater Mpigi region of Uganda. Extracts were evaluated for their ability to inhibit growth of clinical isolates of multidrug-resistant ESKAPE pathogens. Extracts were also screened for quorum quenching activity against S. aureus, including direct protein output assessment (δ-toxin), and cytotoxicity against human keratinocytes (HaCaT). Putative matches of compounds were elucidated via LC–FTMS for the best-performing extracts. These were extracts of Zanthoxylum chalybeum (Staphylococcus aureus: MIC: 16 μg/mL; Enterococcus faecium: MIC: 32 μg/mL) and Harungana madagascariensis (S. aureus: MIC: 32 μg/mL; E. faecium: MIC: 32 μg/mL) stem bark. Extracts of Solanum aculeastrum root bark and Sesamum calycinum subsp. angustifolium leaves exhibited strong quorum sensing inhibition activity against all S. aureus accessory gene regulator (agr) alleles in absence of growth inhibition (IC50 values: 1–64 μg/mL). The study provided scientific evidence for the potential therapeutic efficacy of these medicinal plants in the Greater Mpigi region used for infections and wounds, with 13 out of 16 species tested being validated with in vitro studies.