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An EmrB multidrug efflux pump in Burkholderia thailandensis with unexpected roles in antibiotic resistance.

ABSTRACT: The antibiotic trimethoprim is frequently used to manage Burkholderia infections, and members of the resistance-nodulation-division (RND) family of efflux pumps have been implicated in multidrug resistance of this species complex. We show here that a member of the distinct Escherichia coli multidrug resistance B (EmrB) family is a primary exporter of trimethoprim in Burkholderia thailandensis, as evidenced by increased trimethoprim sensitivity after inactivation of emrB, the gene that encodes EmrB. We also found that the emrB gene is up-regulated following the addition of gentamicin and that this up-regulation is due to repression of the gene encoding OstR, a member of the multiple antibiotic resistance regulator (MarR) family. The addition of the oxidants H2O2 and CuCl2 to B. thailandensis cultures resulted in OstR-dependent differential emrB expression, as determined by qRT-PCR analysis. Specifically, OstR functions as a rheostat that optimizes emrB expression under oxidizing conditions, and it senses oxidants by a unique mechanism involving two vicinal cysteines and one distant cysteine (Cys3, Cys4, and Cys169) per monomer. Paradoxically, emrB inactivation increased resistance of B. thailandensis to tetracycline, a phenomenon that correlated with up-regulation of an RND efflux pump. These observations highlight the intricate mechanisms by which expression of genes that encode efflux pumps is optimized depending on cellular concentrations of antibiotics and oxidants.

SUBMITTER: Sabrin A

PROVIDER: S-EPMC6369286 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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An EmrB multidrug efflux pump in Burkholderia thailandensis with unexpected roles in antibiotic resistance.

Sabrin Afsana A Gioe Brennan W BW Gupta Ashish A Grove Anne A

The Journal of biological chemistry 20181213 6

The antibiotic trimethoprim is frequently used to manage Burkholderia infections, and members of the resistance-nodulation-division (RND) family of efflux pumps have been implicated in multidrug resistance of this species complex. We show here that a member of the distinct Escherichia coli multidrug resistance B (EmrB) family is a primary exporter of trimethoprim in Burkholderia thailandensis, as evidenced by increased trimethoprim sensitivity after inactivation of emrB</ ...[more]

PMID: 30545940

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Project description:Campylobacter jejuni is a foodborne pathogen that is recognized as the leading cause of human bacterial gastroenteritis. The widespread use of antibiotics in medicine and in animal husbandry has led to an increased incidence of antibiotic resistance in Campylobacter In addition to a role in multidrug resistance (MDR), the Campylobacter CmeABC resistance-nodulation-division (RND)-type efflux pump may be involved in virulence. As a vehicle for pathogenic microorganisms, the protozoan Acanthamoeba is a good model for investigations of bacterial survival in the environment and the molecular mechanisms of pathogenicity. The interaction between C. jejuni 81-176 and Acanthamoeba polyphaga was investigated in this study by using a modified gentamicin protection assay. In addition, a possible role for the CmeABC MDR pump in this interaction was explored. Here we report that this MDR pump is beneficial for the intracellular survival and multiplication of C. jejuni in A. polyphaga but is dispensable for biofilm formation and motility.IMPORTANCE The endosymbiotic relationship between amoebae and microbial pathogens may contribute to persistence and spreading of the latter in the environment, which has significant implications for human health. In this study, we found that Campylobacter jejuni was able to survive and to multiply inside Acanthamoeba polyphaga; since these microorganisms can coexist in the same environment (e.g., on poultry farms), the latter may increase the risk of infection with Campylobacter Our data suggest that, in addition to its role in antibiotic resistance, the CmeABC MDR efflux pump plays a role in bacterial survival within amoebae. Furthermore, we demonstrated synergistic effects of the CmeABC MDR efflux pump and TetO on bacterial resistance to tetracycline. Due to its role in both the antibiotic resistance and the virulence of C. jejuni, the CmeABC MDR efflux pump could be considered a good target for the development of antibacterial drugs against this pathogen.

Dataset Information

An EmrB multidrug efflux pump in Burkholderia thailandensis with unexpected roles in antibiotic resistance.

Publications

An EmrB multidrug efflux pump in <i>Burkholderia thailandensis</i> with unexpected roles in antibiotic resistance.

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