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Author Notes:

Correspondence: Cassandra L. Quave; cquave@emory.edu

Author contributions: MK collected the plant specimens, prepared extracts and performed the antibacterial and cell culture experiments.

RP performed the biofilm experiments.

MK, JL, and HT performed the chemical analysis of active extracts.

HT performed δ-toxin analyses.

CQ and ZM designed and directed the study.

MK and CQ analyzed the data and wrote the manuscript.

All authors read, revised and approved the final manuscript.

Acknowledgments: The following reagents were obtained through BEI Resources, NIAID, NIH as part of the Human Microbiome Project: Enterococcus faecium, Strain 513, HM-959; Enterococcus faecium, Strain E0164, NR-31915.

The following reagents were obtained through BEI Resources, NIAID, NIH: Klebsiella pneumoniae, Isolate 1, NR-15410; Acinetobacter baumannii, Strain Naval-81, NR-17786.

See publication for full list of acknowledgements.

Disclosures: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The content is solely the responsibility of the authors and does not necessarily reflect the official views of NCCIH or NIH.

Subjects:

Research Funding:

This work was supported by a grant from the Higher education commission, government of Pakistan under international research support initiative program (IRSIP), award no:1-8/HEC/HRD/2017/7323.

The work was also supported by a grant from the National Institutes of Health, National Center for Complementary and Integrative Health (R01 AT007052, PI: CQ).

The funding agency had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Pharmacology & Pharmacy
  • medicinal plants
  • biofilm
  • quorum sensing
  • Zanthoxylum armatum
  • delta-toxin
  • STAPHYLOCOCCUS-AUREUS TOXINS
  • ANTIMICROBIAL ACTIVITY
  • ARTEMISIA-ABSINTHIUM
  • NATURAL-PRODUCTS
  • ANTIBIOTIC-RESISTANCE
  • BIOFILM FORMATION
  • MARTYNIA-ANNUA
  • ANTIFUNGAL
  • VALLEY
  • IDENTIFICATION

Antibacterial Properties of Medicinal Plants From Pakistan Against Multidrug-Resistant ESKAPE Pathogens

Tools:

Journal Title:

Frontiers in Pharmacology

Volume:

Volume 9

Publisher:

, Pages 815-815

Type of Work:

Article | Final Publisher PDF

Abstract:

Local people in the Sudhnoti district of Pakistan share a rich practice of traditional medicine for the treatment of a variety of ailments. We selected nine plants from the Sudhnoti ethnopharmacological tradition used for the treatment of infectious and inflammatory disease. Our aim was to evaluate the in vitro anti-infective potential of extracts from these species against multidrug-resistant (MDR) ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species) pathogens. Plant specimens were collected in the Sudhnoti district of Pakistan and vouchers deposited in Pakistan and the USA. Dried bulk specimens were ground into a fine powder and extracted by aqueous decoction and maceration in ethanol. Extracts were assessed for growth inhibitory activity against ESKAPE pathogens and biofilm and quorum sensing activity was assessed in Staphylococcus aureus. Cytotoxicity to human cells was assessed via a lactate dehydrogenase assay of treated human keratinocytes (HaCaTs). Four ethanolic extracts (Zanthoxylum armatum, Adiantum capillus-venaris, Artemisia absinthium, and Martynia annua) inhibited the growth of MDR strains of ESKAPE pathogens (IC50: 256 μg mL-1). All extracts, with the exception of Pyrus pashia and M. annua, exhibited significant quorum quenching in a reporter strain for S. aureus agr I. The ethanolic extract of Z. armatum fruits (Extract 1290) inhibited quorum sensing (IC50 32-256 μg mL-1) in S. aureus reporter strains for agr I-III. The quorum quenching activity of extract 1290 was validated by detection of δ-toxin in the bacterial supernatant, with concentrations of 64-256 μg mL-1 sufficient to yield a significant drop in δ-toxin production. None of the extracts inhibited S. aureus biofilm formation at sub-inhibitory concentrations for growth. All extracts were well tolerated by human keratinocytes (LD50 ≥ 256 μg mL-1). Chemical analysis of extract 1290 by liquid chromatography-Fourier transform mass spectrometry (LC-FTMS) revealed the presence of 29 compounds, including eight with putative structural matches. In conclusion, five out of the nine selected anti-infective medicinal plants exhibited growth inhibitory activity against at least one MDR ESKAPE pathogen at concentrations not harmful to human keratinocytes. Furthermore, Z. armatum was identified as a source of quorum quenching natural products and further bioassay-guided fractionation of this species is merited.

Copyright information:

© 2018 Khan, Tang, Lyles, Pineau, Mashwani and Quave.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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