Host - Bacterial Pathogen Communication: The Wily Role of the Multidrug Efflux Pumps of the MFS Family.

Martina Pasqua,Maria Carmela Bonaccorsi Di Patti,Gianni Prosseda,Rita Trirocco,Milena Grossi,Bianca Colonna,Yoko Eguchi,Giulia Fanelli,Ryutaro Utsumi

doi:10.3389/fmolb.2021.723274

Abstract

Bacterial pathogens are able to survive within diverse habitats. The dynamic adaptation to the surroundings depends on their ability to sense environmental variations and to respond in an appropriate manner. This involves, among others, the activation of various cell-to-cell communication strategies. The capability of the bacterial cells to rapidly and co-ordinately set up an interplay with the host cells and/or with other bacteria facilitates their survival in the new niche. Efflux pumps are ubiquitous transmembrane transporters, able to extrude a large set of different molecules. They are strongly implicated in antibiotic resistance since they are able to efficiently expel most of the clinically relevant antibiotics from the bacterial cytoplasm. Besides antibiotic resistance, multidrug efflux pumps take part in several important processes of bacterial cell physiology, including cell to cell communication, and contribute to increase the virulence potential of several bacterial pathogens. Here, we focus on the structural and functional role of multidrug efflux pumps belonging to the Major Facilitator Superfamily (MFS), the largest family of transporters, highlighting their involvement in the colonization of host cells, in virulence and in biofilm formation. We will offer an overview on how MFS multidrug transporters contribute to bacterial survival, adaptation and pathogenicity through the export of diverse molecules. This will be done by presenting the functions of several relevant MFS multidrug efflux pumps in human life-threatening bacterial pathogens as Staphylococcus aureus, Listeria monocytogenes, Klebsiella pneumoniae, Shigella/E. coli, Acinetobacter baumannii.

Highlights

Efflux pumps are ubiquitous transmembrane transporters able to extrude a variety of toxic compounds, including drugs from the cell (Nikaido and Pagès, 2012; Du et al, 2018; Henderson et al, 2021)
multidrug resistance (MDR) efflux pump (EP) have been identified within all major families of transporters, i.e., the Resistance Nodulation Division (RND), the ATP Binding Cassette (ABC), the Major Facilitator Superfamily (MFS), the Multidrug and Toxic Compound Extrusion (MATE), the Drug/Metabolite transporter (DMT), the Proteobacterial Antimicrobial Compound Efflux (PACE) family and the p-aminobenzoyl-glutamate Transporter (Henderson et al, 2021)
Studying the interplay between bacteria and hosts is an effective approach to fully understand the physiological significance of MDR EPs

Summary

Introduction

Efflux pumps are ubiquitous transmembrane transporters able to extrude a variety of toxic compounds, including drugs from the cell (Nikaido and Pagès, 2012; Du et al, 2018; Henderson et al, 2021). Several reports highlight the involvement of MDR EPs of the MFS family in the interaction of several bacterial pathogens with their target host cells (Bigi et al, 2004; Crimmins et al, 2008; Sahu et al, 2012a; Truong-Bolduc et al, 2014; PérezVarela et al, 2017; Pasqua et al, 2019a; Briaud et al, 2019).

Results

Conclusion