Typhinamycin – A Novel Phytochemical from Rhus typhina Extract Exhibits Antimicrobial Activity Toward ESKAPE Pathogens

Abstract

Antibiotic resistance is a leading contributor of the worsening public health crisis of the 21^st century.  Several medically-relevant bacteria are resistant to available antibiotics, especially the ESKAPE pathogens (Enterococcus sp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species).   While very few new antibiotics are in development, discovery of novel antibiotic agents is imperative to combat this threat.  Natural products represent a revived area of interest as a potential source for new antimicrobials. Previous screening of ethanolic extract of Rhus typhina (Staghorn sumac) indicated that this material exhibited marked growth inhibition against 4/6 ESKAPE pathogens at 24 hrs.  A novel methoxylated derivative of fisetin (Typhinamycin) from the extract was isolated, identified, and tested for antimicrobial activity against the ESKAPE pathogens.  In a microtiter plate containing rich growth media inoculated with equivalent levels of bacteria, serial dilutions of Typhinamycin were added to evaluate antibacterial activity. After incubation at 37°C, bacterial growth was measured using a plate reader.  Wells lacking treatment were used to identify normal growth levels.  Preliminary results indicate Typhinamycin produces substantial inhibition of all ESKAPE pathogens. Future investigations will involve the characterization and a detailed analysis of the antimicrobial efficacy of this compound. (Supported by NIH Grant P20GM103434 to the West Virginia IDeA Network for Biomedical Research Excellence)