Abstract
Bacterial infections pose a serious public health concern, especially when an infectious disease has a multidrug resistant causative agent. Such multidrug resistant bacteria can compromise the clinical utility of major chemotherapeutic antimicrobial agents. Drug and multidrug resistant bacteria harbor several distinct molecular mechanisms for resistance. Bacterial antimicrobial agent efflux pumps represent a major mechanism of clinical resistance. The major facilitator superfamily (MFS) is one of the largest groups of solute transporters to date and includes a significant number of bacterial drug and multidrug efflux pumps. We review recent work on the modulation of multidrug efflux pumps, paying special attention to those transporters belonging primarily to the MFS.
Highlights
Drug and multidrug resistant bacterial pathogens that are causative agents of infectious disease constitute a serious public health concern
Some of the common diseases and infections caused by pathogenic strains of bacteria include food poisoning caused by Escherichia coli and Salmonella [1,2,3,4,5,6], gastritis and ulcers caused by Helicobacter pylori [7], the sexually transmitted disease gonorrhea caused by Neisseria gonorrhoeae [8], meningitis caused by N. meningitides [9], skin infections like boils, cellulitis, abscesses, wound infections, toxic shock syndrome, pneumonia, and food poisoning caused by Staphylococcus aureus [10,11,12,13], and pneumonia, meningitis, otitis, and strep throat caused by streptococcal bacteria [14,15,16]
Based on the modes of energy, amino acid sequence similarities, predicted secondary protein structures, known 3D crystal protein structures, and phylogenetic relationships, bacterial drug efflux transporters are classified into five different major superfamilies and are shown in Figure 2: (i) the major facilitator superfamily (MFS) [58, 71]; (ii) the ATP-binding cassette (ABC) superfamily [72, 73]; (iii) the small multidrug resistance (SMR) superfamily [74]; (iv) the resistance-nodulation-cell division (RND) superfamily [75, 76]; and (v) the multidrug and toxic compound extrusion superfamily (MATE) of transporters [69]
Summary
Drug and multidrug resistant bacterial pathogens that are causative agents of infectious disease constitute a serious public health concern. Bacterial multidrug efflux pump systems of the major facilitator superfamily (MFS) and resistancenodulation-cell division (RND) superfamily represent common mechanisms for bacterial resistance to antimicrobial agents. As such these bacterial transporters make suitable targets for modulation in order to restore the clinical efficacy of relevant chemotherapeutic antibacterial agents. We briefly review the drug transporter systems of the MFS (and to a lesser extent the RND superfamily) and discuss their modulation via regulation of expression and efflux pump transport inhibition
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
