The Structural and Functional Study of Efflux Pumps Belonging to the RND Transporters Family from Gram-Negative Bacteria

Dear Colleagues,

Antimicrobial-resistant bacterial infections are a major and costly public health concern. Several pathogens are already pan-resistant, representing a major cause of mortality in patients suffering from nosocomial infections. Drug efflux pumps, which remove compounds from the bacterial cell, thereby lowering antimicrobial concentration to subtoxic levels, play a major role in multidrug resistance.

Gram-negative bacteria are particularly resistant, and some are identified by the World Health Organization as the most urgent priority of pathogens in need of new antimicrobial drug discovery. The clinically most relevant efflux pumps in Gram-negative bacteria belong to the RND (resistance nodulation cell division) family that forms a tripartite macromolecular assembly spanning both membranes and the periplasmic space of Gram-negative organisms. Along with functional studies and in silico approaches, many structures of the individual components, as well as that of the fully assembled pumps from several pathogens, have been solved. Nevertheless, a lot of questions concerning the assembly and the mechanism of efflux remain, and there are still no inhibitors of efflux pumps available in clinical treatment. 

In this Special Issue, we would like to present up-to-date knowledge of the mechanism of these efflux pumps, the identification and characterization of RND efflux pumps from emerging pathogens and their role in antimicrobial resistance, as well as progress made on the development of specific inhibitors (including the development of in vitro or in vivo tools for inhibitor selection). This collection of data could serve as a basis for antimicrobial drug discovery aimed at inhibiting drug efflux pumps to reverse resistance in some of the most resistant pathogens.

Dr. Isabelle Broutin
Prof. Attilio V Vargiu
Prof. Dr. Henrietta Venter
Dr. Gilles Phan
Guest Editors

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