Role, Structure, and Function of Multidrug Efflux Pumps in Gram-Negative Bacteria

Abstract

Genomes of gram-negative bacteria usually contain multiple copies of genes belonging to each of the families of multidrug transporters, such as SMR (small multidrug resistance), MFS (major facilitator superfamily), MATE (multidrug and toxic compound extrusion), and RND (resistance nodulation division). Due to the predominant role RND pumps play in the resistance (both intrinsic and acquired) to commonly used antibiotics, this chapter discusses the pumps of this type in detail; however, the discussion is limited to E. coli and Pseudomonas aeruginosa, as representative organisms. For soil and water dwellers, it is difficult to pinpoint the “natural” substrate for their main efflux pumps. However, gram-negative bacteria have always faced toxic chemicals in the environment, and outer membrane (OM) cannot completely shut out lipophilic compounds, which can diffuse, albeit slowly, across the asymmetric bilayer of OM. Living in a natural habitat surrounded by high concentrations of bile salts and other antimicrobial inhibitors such as fatty acids, E. coli cells are armed with the OM as well as a wide range of efflux pumps. In E. coli, acrR, which is divergently transcribed from the acrAB genes, encodes a repressor. Perhaps because the inactivation of AcrR results in a too high level of production of AcrAB, it seems to serve only a subsidiary role in the regulation of AcrAB expression.