Article,
Targeting bioenergetics is key to counteracting the drug-tolerant state of biofilm-grown bacteria
PLoS Pathog, 16 (12): 1-22 (December 2020)
Abstract
Author summary At sub-minimal inhibitory concentrations, phenothiazines have been shown to inhibit virulence as well as the formation of biofilms in a wide range of different bacterial pathogens. In this study, we analyzed the anti-bacterial effect of the FDA-approved drug, promethazine, on biofilm-grown Pseudomonas aeruginosa. We demonstrate that PMZ interferes with bacterial bioenergetics and sensitizes biofilm-grown P. aeruginosa cells to bactericidal activity of several different classes of antibiotics by several orders of magnitude. This effect was most pronounced when cells were grown under environmental conditions that induce low intracellular proton levels. Thus, it seems that a reduced proton efflux in cells that exhibit decreased respiratory activity due to their biofilm mode of growth might explain their general antimicrobial tolerance. The use of PMZ as an antibiotic sensitizer holds promise that targeting tolerance mechanisms of biofilm-grown bacteria could become a practicable way to change the way physicians treat biofilm-associated infections.
