Bacterial Multidrug Efflux Pumps at the Frontline of Antimicrobial Resistance: An Overview

Abstract

Multidrug efflux pumps function at the frontline to protect bacteria against antimicrobials by decreasing the intracellular concentration of drugs. This protective barrier consists of a series of transporter proteins, which are located in the bacterial cell membrane and periplasm and remove diverse extraneous substrates, including antimicrobials, organic solvents, toxic heavy metals, etc., from bacterial cells. This review systematically and comprehensively summarizes the functions of multiple efflux pumps families and discusses their potential applications. The biological functions of efflux pumps including their promotion of multidrug resistance, biofilm formation, quorum sensing, and survival and pathogenicity of bacteria are elucidated. The potential applications of efflux pump-related genes/proteins for the detection of antibiotic residues and antimicrobial resistance are also analyzed. Last but not least, efflux pump inhibitors, especially those of plant origin, are discussed.

Gene co-expression network analysis of the human gut commensal bacterium Faecalibacterium prausnitzii in R-Shiny

“…Notably, serine/ threonine and ferrous iron transporters were highly upregulated at the earlier time compared to later, which suggests that available serine, threonine, and ferrous iron are imported into the cell during early growth (Fig 2D and 2E). It was also interesting to observe the upregulation of CG447_14545 at time 3h (Fig 2F ); this gene encodes a multi-antimicrobial extrusion (MATE) efflux transporter, which plays a role in antibiotic resistance as well as potentially in bacterialhost interactions and intercellular signaling [49,50]. Instead, time-point 15h was marked by strong upregulation of CG447_09920 and CG447_06950, which encode energy-coupling factor (ECF) transport S component and DNA polymerase IV, respectively (Fig 2G and 2H).…”

Gene co-expression network analysis of the human gut commensal bacterium Faecalibacterium prausnitzii based on WGCNA in R-Shiny

“…Notably, serine/threonine and ferrous iron transporters were highly upregulated at the earlier time compared to later, which suggests that available serine, threonine, and ferrous iron are imported into the cell during early growth (Fig 2 D and E). It was also interesting to observe the upregulation of CG447_14545 at time 3h (Fig 2 F); this gene encodes a multi-antimicrobial extrusion (MATE) efflux transporter, which plays a role in antibiotic resistance as well as potentially in bacterial-host interactions and intercellular signaling [49,50]. Instead, time-point 15h was marked by strong upregulation of CG447_09920 and CG447_06950, which encode energy-coupling factor (ECF) transport S component and DNA polymerase IV, respectively (Fig 2G and H).…”

What Approaches to Thwart Bacterial Efflux Pumps-Mediated Resistance?

“…The EPs operate as a primary protective barrier against antimicrobial drugs by diminishing the intracellular distribution of the drugs; this defensive barrier involves a variety of transport proteins, lodged both within the cell membrane and the periplasmic space, which expels a range of exogenous and noxious compounds out of the bacterial cells [ 23 ]; this means that bacterial EPs do not simply perform the role of physiological transport, their function is also to compete for survival under external influences. Though certain EPs have unique substrates, some carriers can handle many different types of antimicrobials, thereby promoting MDR [ 24 ].…”

“…Still, the specific mechanics and functional domains of EP transporters remain unclear. Numerous conditions exist that impact the bacterial inner and outer membrane (OM), promote pump activity and favor structural changes of the transporters in the fluid membrane environment [ 23 ]. Regardless, a recent study by Krishnamoorthy et al [ 27 ] displayed an interaction between active EPs and the OM permeability barrier in Burkholderia thailandensis , a non-fermenting motile, Gram-negative bacillus.…”