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      Multidrug Efflux Pumps from Enterobacteriaceae, Vibrio cholerae and Staphylococcus aureus Bacterial Food Pathogens

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          Abstract

          Foodborne illnesses caused by bacterial microorganisms are common worldwide and constitute a serious public health concern. In particular, microorganisms belonging to the Enterobacteriaceae and Vibrionaceae families of Gram-negative bacteria, and to the Staphylococcus genus of Gram-positive bacteria are important causative agents of food poisoning and infection in the gastrointestinal tract of humans. Recently, variants of these bacteria have developed resistance to medically important chemotherapeutic agents. Multidrug resistant Escherichia coli, Salmonella enterica, Vibrio cholerae, Enterobacter spp., and Staphylococcus aureus are becoming increasingly recalcitrant to clinical treatment in human patients. Of the various bacterial resistance mechanisms against antimicrobial agents, multidrug efflux pumps comprise a major cause of multiple drug resistance. These multidrug efflux pump systems reside in the biological membrane of the bacteria and actively extrude antimicrobial agents from bacterial cells. This review article summarizes the evolution of these bacterial drug efflux pump systems from a molecular biological standpoint and provides a framework for future work aimed at reducing the conditions that foster dissemination of these multidrug resistant causative agents through human populations.

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          Most cited references359

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          Bacterial Biofilms: A Common Cause of Persistent Infections

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            Molecular basis of bacterial outer membrane permeability revisited.

            Gram-negative bacteria characteristically are surrounded by an additional membrane layer, the outer membrane. Although outer membrane components often play important roles in the interaction of symbiotic or pathogenic bacteria with their host organisms, the major role of this membrane must usually be to serve as a permeability barrier to prevent the entry of noxious compounds and at the same time to allow the influx of nutrient molecules. This review summarizes the development in the field since our previous review (H. Nikaido and M. Vaara, Microbiol. Rev. 49:1-32, 1985) was published. With the discovery of protein channels, structural knowledge enables us to understand in molecular detail how porins, specific channels, TonB-linked receptors, and other proteins function. We are now beginning to see how the export of large proteins occurs across the outer membrane. With our knowledge of the lipopolysaccharide-phospholipid asymmetric bilayer of the outer membrane, we are finally beginning to understand how this bilayer can retard the entry of lipophilic compounds, owing to our increasing knowledge about the chemistry of lipopolysaccharide from diverse organisms and the way in which lipopolysaccharide structure is modified by environmental conditions.
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              Major facilitator superfamily.

              The major facilitator superfamily (MFS) is one of the two largest families of membrane transporters found on Earth. It is present ubiquitously in bacteria, archaea, and eukarya and includes members that can function by solute uniport, solute/cation symport, solute/cation antiport and/or solute/solute antiport with inwardly and/or outwardly directed polarity. All homologous MFS protein sequences in the public databases as of January 1997 were identified on the basis of sequence similarity and shown to be homologous. Phylogenetic analyses revealed the occurrence of 17 distinct families within the MFS, each of which generally transports a single class of compounds. Compounds transported by MFS permeases include simple sugars, oligosaccharides, inositols, drugs, amino acids, nucleosides, organophosphate esters, Krebs cycle metabolites, and a large variety of organic and inorganic anions and cations. Protein members of some MFS families are found exclusively in bacteria or in eukaryotes, but others are found in bacteria, archaea, and eukaryotes. All permeases of the MFS possess either 12 or 14 putative or established transmembrane alpha-helical spanners, and evidence is presented substantiating the proposal that an internal tandem gene duplication event gave rise to a primordial MFS protein prior to divergence of the family members. All 17 families are shown to exhibit the common feature of a well-conserved motif present between transmembrane spanners 2 and 3. The analyses reported serve to characterize one of the largest and most diverse families of transport proteins found in living organisms.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Environ Res Public Health
                Int J Environ Res Public Health
                ijerph
                International Journal of Environmental Research and Public Health
                MDPI
                1661-7827
                1660-4601
                28 January 2015
                February 2015
                : 12
                : 2
                : 1487-1547
                Affiliations
                [1 ]Department of Biology, Eastern New Mexico University, Portales, NM 88130, USA; E-Mails: jodyandersen@ 123456rocketmail.com (J.L.A.); prathusha.kakarla@ 123456enmu.edu (P.K.); najranaa@ 123456gmail.com (R.K.C.); munmun.mukherjee@ 123456enmu.edu (M.M.M.); indrika.ranaweera@ 123456enmu.edu (I.R.); ugina.shrestha@ 123456enmu.edu (U.S.)
                [2 ]Department of Clinical Laboratory and Nutritional Sciences, University of Massachusetts Lowell, Lowell, MA 01854, USA; E-Mails: Guixin_He@ 123456uml.edu (G.H.); ThuyTrang_Tran@ 123456student.uml.edu (T.T.)
                [3 ]QC Laboratory, Harvest and Post-Harvest Technology Division, Central Institute of Fisheries Education (CIFE), Seven Bungalows, Versova, Andheri (W), Mumbai 400061, India; E-Mails: sanathkm@ 123456yahoo.com (S.K.); wslakra@ 123456cife.edu.in (W.S.L.)
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: manuel.varela@ 123456enmu.edu ; Tel.: +1-575-562-2464; Fax: +1-575-5622.
                Article
                ijerph-12-01487
                10.3390/ijerph120201487
                4344678
                25635914
                a8e1632b-0292-4a0c-9639-80558acdf68a
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 16 October 2014
                : 15 January 2015
                Categories
                Review

                Public health
                antimicrobial,bacteria,resistance,efflux pumps,multidrug resistance,food pathogens,staphylococcus aureus,enterobacteriaceae,vibrionaceae,infection

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