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Modulation of Bacterial Multidrug Resistance Efflux Pumps of the Major Facilitator Superfamily

DOI: 10.1155/2013/204141

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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. 1. Introduction 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 resistance-nodulation-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. Here, 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. 2. Bacteria and Pathogenesis Bacteria are unicellular, microscopic living organisms that are rod shaped, ball shaped, or spiral shaped when observed under the microscope. Most bacteria are not harmful; rather, they aid in food preparation and digestion, compete with pathogens, provide vitamins to the body, are useful for basic and applied research purposes, and are important in biotechnology. However, less than one percent of the bacteria of different types are responsible for causing bacterial infections. Bacterial cells are capable of quickly reproducing and releasing chemicals and toxins; pathogenic bacteria can cause damage to cells and tissues in the body and cause clinical disease. Some of the common diseases and infections caused by pathogenic strains of bacteria include food poisoning caused by Escherichia coli and Salmonella [1–6], 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,

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