Role of Multidrug Efflux Pumps in Gram-Positive Bacteria

Abstract

Drug efflux pumps possessed by gram-positive organisms are encoded either by plasmid- or chromosomally-based genes. Generally, drug-specific efflux pumps tend to be located on plasmids and thus are readily transmissible, whereas multidrug (MDR) efflux pumps are usually encoded on the chromosome and are not easily donated to another organism. This chapter focuses the discussion entirely on MDR-type pumps. The available genome sequence data for gram-positive organisms suggests the existence of numerous potential drug pumps in all of them. The greatest amount of information regarding the mechanism(s) of pump function and multidrug recognition as well as the regulation of pump gene expression in gram-positive organisms is available for major facilitator superfamily (MFS) MDR efflux pumps. The study of the mechanism of multidrug recognition and transport is hampered by our general inability to produce high-resolution crystals of MDR pump proteins. Further research on bacterial MDR efflux pumps is warranted in an effort to improve our understanding of how these systems work, because such an understanding may allow the development of means to overcome this resistance mechanism and to recover useful activity of their antibiotic substrates.