Antimicrobial Activity of, and Cellular Pathways Targeted by, p -Anisaldehyde and Epigallocatechin Gallate in the Opportunistic Human Pathogen Pseudomonas aeruginosa

• Published in: Applied and environmental microbiology 2020-02, Vol.86 (4)
• Main Authors: Adewunmi, Yetunde, Namjilsuren, Sanchirmaa, Walker, William D, Amato, Dahlia N, Amato, Douglas V, Mavrodi, Olga V, Patton, Derek L, Mavrodi, Dmitri V
• Format: Article
• Language: English
• Subjects: Acetals; Aldehydes; Anti-Bacterial Agents - pharmacology; Antiinfectives and antibacterials; Antimicrobial activity; Antimicrobial agents; Benzaldehydes - pharmacology; Biosynthesis; Catechin - analogs & derivatives; Catechin - pharmacology; Drug delivery; Drug delivery systems; Drug metabolism; Drug Resistance, Multiple, Bacterial; Efflux; Energy metabolism; Epigallocatechin gallate; Essential oils; Gene expression; Genetics and Molecular Biology; Green tea; Hydrophobicity; Hypersensitivity; Metabolites; Microbial Sensitivity Tests; Microorganisms; Molybdenum; Multidrug resistance; Opportunist infection; Oxidative stress; Pathogens; Plants; Polymers; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Spotlight
• ISSN: 0099-2240; 1098-5336
• DOI: 10.1128/AEM.02482-19

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 -anisaldehyde from star anise into a polymer network called proantimicrobial networks via degradable acetals (PANDAs) and used it as a novel drug delivery platform. PANDAs released -anisaldehyde upon a change in pH and humidity and controlled the growth of the multidrug-resistant pathogen PAO1. In this study, we identified the cellular pathways targeted by -anisaldehyde by generating 10,000 transposon mutants of PAO1 and screened them for hypersensitivity to -anisaldehyde. To improve the antimicrobial efficacy of -anisaldehyde, we combined it with epigallocatechin gallate (EGCG), a polyphenol from green tea, and demonstrated that it acts synergistically with -anisaldehyde in killing We then used transcriptome sequencing to profile the responses of to -anisaldehyde, EGCG, and their combination. The exposure to -anisaldehyde altered the expression of genes involved in modification of the cell envelope, membrane transport, drug efflux, energy metabolism, molybdenum cofactor biosynthesis, and the stress response. We also demonstrate that the addition of EGCG reversed many -anisaldehyde-coping effects and induced oxidative stress. Our results provide insight into the antimicrobial activity of -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. Essential oils (EOs) are plant-derived products that have long been exploited for their antimicrobial activities in medicine, agriculture, and food preservation. EOs represent a promising alternative to conventional antibiotics due to their broad-range antimicrobial activity, low toxicity to human commensal bacteria, and capacity to kill microorganisms without promoting resistance. Despite the progress in the understanding of the biological activity of EOs, our understanding of many aspects of their mode of action remains inconclusive. The overarching aim of this work was to address these gaps by studying the molecular interactions between an antimicrobial plant aldehyde and the opportunistic human pathogen The results of this study identify the microbial genes a