Pentagalloyl glucose from Schinus terebinthifolia inhibits growth of carbapenem-resistant Acinetobacter baumannii

• Type of Material: Article
• Authors: Micah Dettweiler, Emory University; Lewis Marquez, Emory University; Michelle Lin, Emory University; Anne M. Sweeney-Jones, Georgia Institute of Technology; Bhuwan Khatri Chhetri, Georgia Institute of Technology; Daniel V. Zurawski, Walter Reed Army Institute of Research; Julia Kubanek, Georgia Institute of Technology; Cassandra Quave, Emory University
• Language: English
• Date: 2020-09-18
• 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/s41598-020-72331-w
• Title of Journal or Parent Work: SCIENTIFIC REPORTS
• Volume: 10
• Issue: 1
• Start Page: 15340
• End Page: 15340
• Keywords: CASUALTIES; IRON CHELATORS; Science & Technology; PGG; LIPOPOLYSACCHARIDE; IRAQ; Multidisciplinary Sciences; Science & Technology - Other Topics
• Research Categories: Health Sciences, Immunology; Biology, Microbiology

Abstract

The rise of antibiotic resistance has necessitated a search for new antimicrobials with potent activity against multidrug-resistant gram-negative pathogens, such as carbapenem-resistant Acinetobacter baumannii (CRAB). In this study, a library of botanical extracts generated from plants used to treat infections in traditional medicine was screened for growth inhibition of CRAB. A crude extract of Schinus terebinthifolia leaves exhibited 80% inhibition at 256 µg/mL and underwent bioassay-guided fractionation, leading to the isolation of pentagalloyl glucose (PGG), a bioactive gallotannin. PGG inhibited growth of both CRAB and susceptible A. baumannii (MIC 64–256 µg/mL), and also exhibited activity against Pseudomonas aeruginosa (MIC 16 µg/mL) and Staphylococcus aureus (MIC 64 µg/mL). A mammalian cytotoxicity assay with human keratinocytes (HaCaTs) yielded an IC50 for PGG of 256 µg/mL. Mechanistic experiments revealed iron chelation as a possible mode of action for PGG’s activity against CRAB. Passaging assays for resistance did not produce any resistant mutants over a period of 21 days. In conclusion, PGG exhibits antimicrobial activity against CRAB, but due to known pharmacological restrictions in delivery, translation as a therapeutic may be limited to topical applications such as wound rinses and dressings.