Oct 25, 2018

Universal antibiotic tolerance arising from antibiotic-triggered accumulation of redox metabolites

BioRxiv : the Preprint Server for Biology
Kui ZhuLINGCHONG YOU

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen that often infects open wounds or patients with cystic fibrosis. Once established, P. aeruginosa infections are notoriously difficult to eradicate. This difficulty is in part due to the ability of P. aeruginosa to tolerate antibiotic treatment at the individual-cell level or through collective behaviors. Here we describe a new mechanism by which P. aeruginosa tolerates antibiotic treatment by modulating its global cellular metabolism. In particular, treatment of P. aeruginosa with sublethal concentrations of antibiotics covering all major classes promoted accumulation of the redox-sensitive phenazine - pyocyanin (PYO). PYO in turn conferred general tolerance against diverse antibiotics for both P. aeruginosa and other Gram-negative and Gram-positive bacteria. We show that PYO promotes energy generation to enhance the activity of efflux pumps, leading to enhanced antibiotic tolerance. This property is shared by other redox-active phenazines produced by P. aeruginosa. Our discovery sheds new insights into the physiological functions of phenazines and has implications for designing effective antibiotic treatment protocols.

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Mentioned in this Paper

Gram-Positive Bacteria
Metabolic Process, Cellular
Phenazines
Pseudomonas aeruginosa (antigen)
Antibiotic throat preparations
Pathogenic Organism
Antifungal Antibiotics, Topical
Multidrug Efflux Pump Activity
Cystic Fibrosis
Allergens

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