The Varied Role of Efflux Pumps of the MFS Family in the Interplay of Bacteria with Animal and Plant Cells.

Pasqua Pasqua,Micheli Micheli,Fanelli Fanelli,Colonna Colonna,Grossi Grossi,Barras Barras,Zennaro Zennaro,Prosseda Prosseda

doi:10.3390/microorganisms7090285

Abstract

Efflux pumps represent an important and large group of transporter proteins found in all organisms. The importance of efflux pumps resides in their ability to extrude a wide range of antibiotics, resulting in the emergence of multidrug resistance in many bacteria. Besides antibiotics, multidrug efflux pumps can also extrude a large variety of compounds: Bacterial metabolites, plant-produced compounds, quorum-sensing molecules, and virulence factors. This versatility makes efflux pumps relevant players in interactions not only with other bacteria, but also with plant or animal cells. The multidrug efflux pumps belonging to the major facilitator superfamily (MFS) are widely distributed in microbial genomes and exhibit a large spectrum of substrate specificities. Multidrug MFS efflux pumps are present either as single-component transporters or as tripartite complexes. In this review, we will summarize how the multidrug MFS efflux pumps contribute to the interplay between bacteria and targeted host cells, with emphasis on their role in bacterial virulence, in the colonization of plant and animal host cells and in biofilm formation. We will also address the complexity of these interactions in the light of the underlying regulatory networks required for the effective activation of efflux pump genes.

Highlights

Efflux pumps (EPs) are found in all living organisms [1,2,3]
As this poses an enormous threat to public health, multidrug resistance (MDR) EPs have been mainly studied in clinically relevant bacteria
Several investigations suggest that the genes encoding MDR EPs cannot be considered as the result of recent evolution facilitated by intense antimicrobial therapy, but rather appear to be ancient genes encoding cellular transmembrane devices deeply involved in the physiology and ecology of all organisms [3,8,9,10,11,12,13]

Summary

Introduction

Efflux pumps (EPs) are found in all living organisms [1,2,3]. In many bacteria EPs extrude a wide range of antibiotics, strongly contributing to the emergence of multidrug resistance (MDR) [4,5,6,7]. Several investigations suggest that the genes encoding MDR EPs cannot be considered as the result of recent evolution facilitated by intense antimicrobial therapy, but rather appear to be ancient genes encoding cellular transmembrane devices deeply involved in the physiology and ecology of all organisms [3,8,9,10,11,12,13] This view is consistent with the fact that MDR EPs can extrude a large variety of compounds besides antibiotics, e.g., bacterial metabolites, heavy metals, plant signaling compounds, organic pollutants, quorum-sensing molecules, and virulence factors. We describe the main strategies adopted by bacteria to allow efficient and coordinate expression of MFS EPs in response to environmental stimuli

Organization and Evolution of the MFS EPs

Transcriptional Strategies for the Regulation of MFS EPs

Role of MFS EPs in Interactions Between Bacteria and Plant Cells

Role of the MFS EPs in the Virulence of Bacterial Pathogens in Animal Hosts

Role of the MFS EPs in Bacterial Communication and Biofilm Formation

Conclusions