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

• Published in: Scientific reports 2020-07, Vol.10 (1), p.11935-19, Article 11935
• Main Authors: Schultz, Fabien, Anywar, Godwin, Tang, Huaqiao, Chassagne, François, Lyles, James T., Garbe, Leif-Alexander, Quave, Cassandra L.
• Format: Article
• Language: English
• Subjects: 631/326/22; 631/449; 692/308; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; Antibiotic resistance; Bacterial Infections - drug therapy; Bacterial Infections - microbiology; Bark; Cell Survival - drug effects; Chromatography, Liquid; Clinical isolates; Cytotoxicity; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial - drug effects; Drug therapy; Global health; Herbal medicine; Humanities and Social Sciences; Humans; Inflammatory diseases; Keratinocytes; Keratinocytes - drug effects; Keratinocytes - metabolism; Mass Spectrometry; Medicinal plants; Microbial Sensitivity Tests; Minimum inhibitory concentration; multidisciplinary; Multidrug resistance; Pathogens; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant species; Plants, Medicinal - chemistry; Quorum sensing; Quorum Sensing - drug effects; Science; Science (multidisciplinary); Staphylococcus aureus; Staphylococcus aureus - drug effects; Toxins; Uganda
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-67572-8

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 (IC 50  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.