Microbial Efflux of Antibiotics and Inhibitors of Efflux Pumps

Abstract

Detergent-like bile salts kill bacterial cells by destroying bacterial multidrug resistance (MDR) efflux systems. These not only play an important role in antibacterial resistance but also contribute to bacterial pathogenesis. Reserpine and H+/K+ ATPase inhibitors can significantly reduce MICs, increase killing activity, and prolong the postantibiotic effect of fluoroquinolones. Two proteins, NorM and YdhE, are representative of MDR efflux pumps. Resistance nodulation cell division family (RND) transporters are a three-component system. The RND pumps utilize the energy of the proton motive force to extract dyes, detergents, disinfectants, solvents, and antibiotics from the cell. AcrAB appears to regulate primarily by global regulators such as MarA (which responds to the presence of antibiotics or inhibitors). Few antibiotics are effective for the treatment of Acinetobacterinfections due to the numerous mechanisms of resistance and the frequency of MDR strains. Two genes, floR and tetC, encode efflux pumps belonging to the major facilitator superfamily (MFS) family. ATP-binding cassette (ABC) transporters are composed of at least 28 families for sugars, amino acids, ions, drugs, antibiotics, vitamins, iron complexes, peptides, proteins, complex carbohydrates, etc. Efflux pump inhibitors may be novel molecules belonging to a given new chemical family. In addition to being involved in the reduced susceptibility of gram-positive bacteria to fluoroquinolones, efflux pumps contribute to the acquired resistance which is selected upon exposure to the antibacterials.