Abstract
Pathogenic microorganisms that are multidrug-resistant can pose severe clinical and public health concerns. In particular, bacterial multidrug efflux transporters of the major facilitator superfamily constitute a notable group of drug resistance mechanisms primarily because multidrug-resistant pathogens can become refractory to antimicrobial agents, thus resulting in potentially untreatable bacterial infections. The major facilitator superfamily is composed of thousands of solute transporters that are related in terms of their phylogenetic relationships, primary amino acid sequences, two- and three-dimensional structures, modes of energization (passive and secondary active), and in their mechanisms of solute and ion translocation across the membrane. The major facilitator superfamily is also composed of numerous families and sub-families of homologous transporters that are conserved across all living taxa, from bacteria to humans. Members of this superfamily share several classes of highly conserved amino acid sequence motifs that play essential mechanistic roles during transport. The structural and functional importance of multidrug efflux pumps that belong to the major facilitator family and that are harbored by Gram-negative and -positive bacterial pathogens are considered here.
Highlights
Certain microorganisms, such as bacteria, are causative agents of infection [1]
Among the many virulence factors harbored by bacterial pathogens, those with intrinsic and acquired multidrug resistance determinants are refractory to chemotherapy but may serve as potential targets of modulators [5]
We evaluated the efficacy of the garlic extract and its bioactive agent allyl sulfide towards multidrug resistance conferred by the EmrD-3 multidrug efflux pump from the Vibrio cholerae pathogen [128]
Summary
Bacterial pathogens that are resistant to multiple chemotherapeutic antimicrobial agents can constitute serious public health concerns as such microorganisms are potentially untreatable [2,3]. Multidrug efflux pumps serve to provide active resistance to a constellation of otherwise potentially useful antimicrobial agents by actively exporting the agents from the intracellular location of bacteria to the extracellular milieu, where such agents are ineffective [7]. The respective members of each of these superfamilies share related amino acid sequences, secondary and tertiary structures, and even specific modes of energetics that drive their efflux activities [9]. The individual members within their particular superfamily share common ancestral origins and, evolutionarily conserved sequence motifs, which may serve in mechanistic fashions their active efflux properties [10].
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