Efflux Pumps of Burkholderia thailandensis Control the Permeability Barrier of the Outer Membrane

Antimicrobial Agents and Chemotherapy
Ganesh KrishnamoorthyHelen I Zgurskaya

Abstract

Burkholderia comprises species that are significant biothreat agents and common contaminants of pharmaceutical production facilities. Their extreme antibiotic resistance affects all classes of antibiotics, including polycationic polymyxins and aminoglycosides. The major underlying mechanism is the presence of two permeability barriers, the outer membrane with modified lipid A moieties and active drug efflux pumps. The two barriers are thought to be mechanistically independent and act synergistically to reduce the intracellular concentrations of antibiotics. In this study, we analyzed the interplay between active efflux pumps and the permeability barrier of the outer membrane in Burkholderia thailandensis We found that three efflux pumps, AmrAB-OprA, BpeEF-OprC, and BpeAB-OprB, of B. thailandensis are expressed under standard laboratory conditions and provide protection against multiple antibiotics, including polycationic polymyxins. Our results further suggest that the inactivation of AmrAB-OprA or BpeAB-OprB potentiates the antibacterial activities of antibiotics not only by reducing their efflux, but also by increasing their uptake into cells. Mass spectrometry analyses showed that in efflux-deficient B. thailandensis cells, ...Continue Reading

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Citations

Dec 13, 2019·Frontiers in Microbiology·Pradip R PantaWilliam T Doerrler
Feb 5, 2021·Accounts of Chemical Research·Helen I ZgurskayaValentin V Rybenkov
Nov 18, 2020·Nature Chemical Biology·Shibin ZhaoDerek S Tan

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