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

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.

Genetic and Biochemical Characterization of Halogenation and Drug Transportation Genes Encoded in the Albofungin Biosynthetic Gene Cluster

“… Schematic diagram for the functions of OrfA/OrfL and the influences of extracellular matrices. After triggering by a specific external signal, the biosynthesis of albofungin is turned on, wherein the flavin-dependent halogenase OrfA halogenates albofungin, and the MFS efflux pump-like protein OrfL transports the halogenated products outside the cell in a manner similar to the MFS multidrug efflux pumps reported by Pasqua et al ( 39 ). ECM (e.g., lipopolysaccharide [LPS], PIA, and CPS) acting as an antibiotic physical barrier prevents cell wall damage wreaked by albofungins, especially the halogenated products because of high hydrophobicity and less diffusibility ( 43 , 56 , 57 ).…”

“…S9). MFS proteins are often related to metabolite transportation and anti-multidrug resistance in bacteria ( 39 ). In our boundary delimitation for the abf BGC ( Fig.…”

Comprehensive Genomic Analysis of Marine Strain Streptomyces sp. 891, an Excellent Producer of Chrysomycin A with Therapeutic Potential

“…Besides that, three unknown genes were integrated in the chry891 cluster, and premised on their conserved domains, chry891_X a was most likely emrB , encoding a DHA2 family efflux MFS (major facilitator superfamily) transporter permease subunit. As the largest family of transporters, the MFS is a typical type of multidrug resistance efflux pump, associated closely with antibiotic resistance and taking part in several important processes of bacterial cell physiology, including cell to cell communication, and increasing the virulence potential of several bacterial pathogens [ 27 ]. Chry891_X b and chry891_X c were predicted to encode 4′-phosphopantetheinyl transferase superfamily protein and FAD-dependent monooxygenase, which are important co-factors of secondary metabolite biosynthesis catalytic enzymes.…”

Thymol as an Adjuvant to Restore Antibiotic Efficacy and Reduce Antimicrobial Resistance and Virulence Gene Expression in Enterotoxigenic Escherichia coli Strains

“…In general, the data showed that thymol’s supportive action on tetracycline mainly takes place through the modulation of antibiotic movement across bacterial membranes rather than directly affecting the genetic expression of efflux pumps. As a confirmation, tetA was not influenced by the addition of thymol, and no ameliorative effects were registered for the emrKY-tolC system, a multidrug efflux pump [ 59 ]. In particular, the expression of the chromosomal emrKY-tolC genes is tightly regulated by phoPQ- and evgAS -sensing systems and is influenced by several negative feedback mechanisms [ 59 , 60 ].…”

“…As a confirmation, tetA was not influenced by the addition of thymol, and no ameliorative effects were registered for the emrKY-tolC system, a multidrug efflux pump [ 59 ]. In particular, the expression of the chromosomal emrKY-tolC genes is tightly regulated by phoPQ- and evgAS -sensing systems and is influenced by several negative feedback mechanisms [ 59 , 60 ]. It is possible that, as already discussed for colistin’s chromosomal resistance determinants, in our culture conditions, ETEC bacteria experienced downregulation of such efflux pumps after their initial activation, an effect that would be maintained with thymol.…”