What do Proton Motive Force Driven Multidrug Resistance Transporters Have in Common?

Piotr Mazurkiewicz,Arnold J.m Driessen ,Wil N Konings

doi:10.21775/cimb.007.007

Abstract

The extensive progress of genome sequencing projects in recent years has demonstrated that multidrug resistance (MDR) transporters are widely spread among all domains of life. This indicates that they play crucial roles in the survival of organisms. Moreover, antibiotic and chemotherapeutic treatments have revealed that microorganisms and cancer cells may use MDR transporters to fight the cytotoxic action of drugs. Currently, several MDR extrusion systems are being investigated in detail. It is expected that understanding of the molecular basis of multidrug recognition and the transport mechanisms will allow a more rational design of new drugs which either will not be recognized and expelled by or will efficiently inhibit the activity of the MDR transporters. MDR transporters either utilize ATP hydrolysis or an ion motive force as an energy source to drive drugs out of the cell. This review summarizes the recent progress in the field of bacterial proton motive force driven MDR transporters.

Highlights

Bacteria are frequently challenged in their environment by numerous toxic compounds, which range from natural compounds, peptides, noxious metabolic products, and secondary metabolites, to industrially produced chemicals such as organic solvents
Pmf and smf driven multidrug resistance (MDR) transporters are found in four families: the Major Facilitator Superfamily (MFS) (Marger and Saier, 1993), the Small Multidrug Resistance (SMR) family (Paulsen et al, 1996c), the ResistanceNodulation-cell Division (RND) family (Saier et al, 1994), and the Multi Antimicrobial Extrusion (MATE) family (Brown et al, 1999) (Fig. 1)
The pmf driven MDR transporters are a very diverse group of transporters composed of members of three large families: the Small Multidrug Resistance family, the Major Facilitator Superfamily and the Resistance-Nodulation-cell

Summary

Introduction

Bacteria are frequently challenged in their environment by numerous toxic compounds, which range from natural compounds (e.g. plant alkaloids), peptides (e.g. bacteriocins), noxious metabolic products (e.g. bile salts and fatty acids in the case of enteric bacteria), and secondary metabolites (e.g. antibiotics), to industrially produced chemicals such as organic solvents. In the MFS-MDR transporters LmrP of L. lactis (Mazurkiewicz et al, 2002; Mazurkiewicz et al, 2004b) MdfA of E. coli (Edgar and Bibi, 1999; Adler and Bibi, 2003) and QacA of S. aureus (Paulsen et al, 1996a) residues important for the substrate specificity can be found both in the N- and C-terminal halves of proteins.

Results

Conclusion