Document Type

Article

Publication Date

12-6-2019

Department

Biological Sciences

School

Biological, Environmental, and Earth Sciences

Abstract

Plant-derived aldehydes are constituents of essential oils that possess broad-spectrum antimicrobial activity and kill microorganisms without promoting resistance. In our previous study, we incorporated p-anisaldehyde from star anise into a polymer network called PANDAs (Pro-Antimicrobial Networks via Degradable Acetals) and used it as a novel drug delivery platform. PANDAs released p-anisaldehyde upon a change in pH and humidity, and controlled growth of the multi-drug resistant pathogen Pseudomonas aeruginosa PAO1. In this study, we identified cellular pathways targeted by p-anisaldehyde, by generating 10,000 transposon mutants of PAO1 and screened them for hypersensitivity to p-anisaldehyde. To improve the antimicrobial efficacy of p-anisaldehyde, we combined it with epigallocatechin gallate (EGCG), a polyphenol from green tea, and demonstrated that it acts synergistically with p-anisaldehyde in killing P. aeruginosa. We then used RNA-seq to profile transcriptomic responses of P. aeruginosa to p-anisaldehyde, EGCG, and their combination. The exposure to p-anisaldehyde altered the expression of genes involved in the modification of cell envelope, membrane transport, drug efflux, energy metabolism, molybdenum cofactor biosynthesis, and stress response. We also demonstrated that the addition of EGCG reversed many p-anisaldehyde-coping effects and induced oxidative stress. Our results provide an insight into the antimicrobial activity of p-anisaldehyde and its interactions with EGCG and may aid in the rational identification of new synergistically-acting combinations of plant metabolites. Our study also confirms the utility of the thiol-ene polymer platform for the sustained and effective delivery of hydrophobic and volatile antimicrobial compounds.

Comments

This is the peer reviewed version of the following article: "The Antimicrobial Activity Targeted by p-anisaldehyde and Epigallocatechin Gallate in the Opportunistic Human Pathogen Pseudomonas aeruginosa," which has been published in final form at 10.1128/AEM.02482-19.

Publication Title

Applied and Environmental Microbiology

Available for download on Saturday, June 06, 2020

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