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Daneng Wang - One of the best experts on this subject based on the ideXlab platform.
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Ins and Outs of Major Facilitator Superfamily Antiporters
Annual review of microbiology, 2008Co-Authors: Christopher J. Law, Peter C. Maloney, Daneng WangAbstract:The Major Facilitator Superfamily (MFS) represents the largest group of secondary active membrane transporters, and its members transport a diverse range of substrates. Recent work shows that MFS antiporters, and perhaps all members of the MFS, share the same three-dimensional structure, consisting of two domains that surround a substrate translocation pore. The advent of crystal structures of three MFS antiporters sheds light on their fundamental mechanism; they operate via a single binding site, alternating-access mechanism that involves a rocker-switch type movement of the two halves of the protein. In the sn-glycerol-3-phosphate transporter (GlpT) from Escherichia coli, the substrate-binding site is formed by several charged residues and a histidine that can be protonated. Salt-bridge formation and breakage are involved in the conformational changes of the protein during transport. In this review, we attempt to give an account of a set of mechanistic principles that characterize all MFS antiporters.
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the structural basis of substrate translocation by the escherichia coli glycerol 3 phosphate transporter a member of the Major Facilitator Superfamily
Current Opinion in Structural Biology, 2004Co-Authors: Joanne M Lemieux, Yafei Huang, Daneng WangAbstract:The Major Facilitator Superfamily represents the largest group of secondary active membrane transporters in the cell. The 3.3A resolution structure of a member of this protein Superfamily, the glycerol-3-phosphate transporter from the Escherichia coli inner membrane, reveals two domains connected by a long central loop. These N- and C-terminal domains, each containing a six-helix bundle, are related by pseudo-twofold symmetry. A substrate translocation pore is located between the two domains and is open to the cytoplasm. Two arginines at the closed end of the pore comprise the substrate-binding site. Biochemical experiments show that, upon substrate binding, the protein adopts a more compact conformation. The crystal structure suggests that the transporter operates through a single binding site, alternating access mechanism via a rocker-switch type of movement of the N- and C-terminal domains. The structure and mechanism of the glycerol-3-phosphate transporter form a paradigm for other members of the Major Facilitator Superfamily.
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three dimensional crystallization of the escherichia coli glycerol 3 phosphate transporter a member of the Major Facilitator Superfamily
Protein Science, 2003Co-Authors: Joanne M Lemieux, Manfred Auer, Anthony Villa, Jinmei Song, Myong Jin Kim, Yafei Huang, Daneng WangAbstract:Here we report the successful three-dimensional crystallization of GlpT, the glycerol-3-phosphate transporter from Escherichia coli inner membrane. GlpT possesses 12 transmembrane -helices and is a member of the Major Facilitator Superfamily. It mediates the exchange of glycerol-3-phosphate for inorganic phosphate across the membrane. Approximately 20 phospholipid molecules per protein, identified as negatively charged phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin, were required for the monodispersity of purified GlpT. Analytical size-exclusion chromatography proved to be efficient in identifying detergents for GlpT monodispersity. Nine such detergents were later used for GlpT crystallization. Screening for crystal nucleation was carried out with a variety of polyethylene glycols as the precipitant over a wide pH range. Subsequent identification of a rigid protein core by limited proteolysis and mass spectroscopy resulted in better-ordered crystals. These crystals exhibited orde rt o 3.7A resolution in two dimensions. However, the stacking in the third dimension was partially disordered. This stacking problem was overcome by using a detergent mixture and manipulating the ionic interactions in the crystallization solution. The resulting GlpT crystals diffracted isotropically to 3.3 A resolution and were suitable for structure determination by X-ray crystallography.
Manuel F. Varela - One of the best experts on this subject based on the ideXlab platform.
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functional and structural roles of the Major Facilitator Superfamily bacterial multidrug efflux pumps
Microorganisms, 2020Co-Authors: Sanath Kumar, Manjusha Lekshmi, Ammini Parvathi, Manisha Ojha, Nicholas Wenzel, Manuel F. VarelaAbstract: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.
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modulation of antimicrobial efflux pumps of the Major Facilitator Superfamily in staphylococcus aureus
microbiology 2018 Vol. 4 Pages 1-18, 2018Co-Authors: Manjusha Lekshmi, Sanath Kumar, Ugina Shrestha, Parvathi Ammini, Jones Adjei, Leslie M Sanford, Manuel F. VarelaAbstract:Variants of the microorganism Staphylococcus aureus which are resistant to antimicrobial agents exist as causative agents of serious infectious disease and constitute a considerable public health concern. One of the main antimicrobial resistance mechanisms harbored by S. aureus pathogens is exemplified by integral membrane transport systems that actively remove antimicrobial agents from bacteria where the cytoplasmic drug targets reside, thus allowing the bacteria to survive and grow. An important class of solute transporter proteins, called the Major Facilitator Superfamily, includes related and homologous passive and secondary active transport systems, many of which are antimicrobial efflux pumps. Transporters of the Major Facilitator Superfamily, which confer antimicrobial efflux and bacterial resistance in S. aureus, are good targets for development of resistance-modifying agents, such as efflux pump inhibition. Such modulatory action upon these antimicrobial efflux systems of the Major Facilitator Superfamily in S. aureus may circumvent resistance and restore the clinical efficacy of therapy towards S. aureus infection.
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Bacterial Multidrug Efflux Pumps of the Major Facilitator Superfamily as Targets for Modulation
Infectious disorders drug targets, 2016Co-Authors: Sanath Kumar, Gui-xin He, Prathusha Kakarla, Ugina Shrestha, Ranjana Kc, Indrika Ranaweera, T. Mark Willmon, Sharla R. Barr, Alberto J. Hernandez, Manuel F. VarelaAbstract:Abstract Causative agents of infectious disease that are multidrug resistant bacterial pathogens represent a serious public health concern due to the increasingly difficult nature of achieving efficacious clinical treatments. Of the various acquired and intrinsic antimicrobial agent resistance determinants, integral-membrane multidrug efflux pumps of the Major Facilitator Superfamily constitute a Major mechanism of bacterial resistance. The Major Facilitator Superfamily (MFS) encompasses thousands of known related secondary active and passive solute transporters, including multidrug efflux pumps, from bacteria to humans. This review article addresses recent developments involving the targeting by various modulators of bacterial multidrug efflux pumps from the Major Facilitator Superfamily. It is currently of tremendous interest to modulate bacterial multidrug efflux pumps in order to eventually restore the clinical efficacy of therapeutic agents against recalcitrant bacterial infections. Such MFS multidrug efflux pumps are good targets for modulation.
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structural comparison of bacterial multidrug efflux pumps of the Major Facilitator Superfamily
Trends in cell & molecular biology, 2015Co-Authors: Indrika Ranaweera, Prathusha Kakarla, Ugina Shrestha, Sharla R. Barr, Alberto J. Hernandez, K C Ranjana, Mark T Willmon, Munmun Mukherjee, Manuel F. VarelaAbstract:The biological membrane is an efficient barrier against water-soluble substances. Solute transporters circumvent this membrane barrier by transporting water-soluble solutes across the membrane to the other sides. These transport proteins are thus required for all living organisms. Microorganisms, such as bacteria, effectively exploit solute transporters to acquire useful nutrients for growth or to expel substances that are inhibitory to their growth. Overall, there are distinct types of related solute transporters that are grouped into families or superfamilies. Of these various transporters, the Major Facilitator Superfamily (MFS) represents a very large and constantly growing group and are driven by solute- and ion-gradients, making them passive and secondary active transporters, respectively. Members of the Major Facilitator Superfamily transport an extreme variety of structurally different substrates such as antimicrobial agents, amino acids, sugars, intermediary metabolites, ions, and other small molecules. Importantly, bacteria, especially pathogenic ones, have evolved multidrug efflux pumps which belong to the Major Facilitator Superfamily. Furthermore, members of this important Superfamily share similar primary sequences in the form of highly conserved sequence motifs that confer useful functional properties during transport. The transporters of the Superfamily also share similarities in secondary structures, such as possessing 12- or 14-membrane spanning α-helices and the more recently described 3-helix structure repeat element, known as the MFS fold. The three-dimensional structures of bacterial multidrug efflux pumps have been determined for only a few members of the Superfamily, all drug pumps of which are surprisingly from Escherichia coli. This review briefly summarizes the structural properties of the bacterial multidrug efflux pumps of the Major Facilitator Superfamily in a comparative manner and provides future directions for study.
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modulation of bacterial multidrug resistance efflux pumps of the Major Facilitator Superfamily
International Journal of Bacteriology, 2013Co-Authors: Sanath Kumar, Munmun Mukherjee, Manuel F. VarelaAbstract: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.
Milton H Saier - One of the best experts on this subject based on the ideXlab platform.
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conserved movement of tms11 between occluded conformations of lacy and xyle of the Major Facilitator Superfamily suggests a similar hinge like mechanism
Proteins, 2015Co-Authors: Ake Vastermark, Adelle Driker, Milton H SaierAbstract:The Δ-distance maps can detect local remodeling that is difficult to accurately determine using superimpositions. Transmembrane segments (TMSs) 11 in both LacY and XylE of the Major Facilitator Superfamily uniquely contribute the greatest amount of mobile surface area in the outward-occluded state and undergo analogous movements. The intracellular part of TMS11 moves away from the C-terminal domain and into the substrate cavity during the conformational change from the outward-occluded to the inward-occluded state. A difference was noted between LacY and XylE when they assumed the inward open state after releasing a substrate to the inside in which TMS11 of LacY moved further into the substrate release space, whereas in XylE, TMS11 slightly retracted into the C-terminal domain. Independent movement of the N-terminal half of TMS11 suggests that it is flexible in the middle. Repeat-swapped homology modeling was used to discover that a loop connecting TMSs 10 and 11 in LacY probably moves during the transition between the unavailable outward-open state and the outward-occluded state. TMSs 11 and the other elements displaying a notable domain-independent movement colocalize with the interdomain linker, suggesting that these elements could drive the alternating access movement between the domain halves. Preliminary evidence indicates that analogous movements occur in other members of the Major Facilitator Superfamily.
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Major Facilitator Superfamily mfs evolved without 3 transmembrane segment unit rearrangements
Proceedings of the National Academy of Sciences of the United States of America, 2014Co-Authors: Ake Vastermark, Milton H SaierAbstract:Based on alleged functional residue correspondences, a recent study proposed a model of 3-transmembrane segment (TMS) repeat unit rearrangements in Major Facilitator Superfamily (MFS) carriers (1). A rebuttal of “Evolutionary mix-and-match with MFS transporters” (1) is currently in press in the Journal of Molecular Microbiology and Biotechnology (2). In their follow-up paper, “Evolutionary mix-and-match with MFS transporters II” (3), Madej and Kaback extend their postulate (1) to xylose (XylE), peptide (PepT) (4), and phosphate (PiPT) (5) porters by suggesting additional 3-TMS unit rearrangements (3). In this letter, we suggest that these transporters are all homologous throughout their lengths, having evolved from a common ancestor without 3-TMS unit rearrangements.
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the Major Facilitator Superfamily mfs revisited
FEBS Journal, 2012Co-Authors: Vamsee S Reddy, Maksim A Shlykov, Rostislav Castillo, Eric I Sun, Milton H SaierAbstract:The Major Facilitator Superfamily (MFS) is the largest known Superfamily of secondary carriers found in the biosphere. It is ubiquitously distributed throughout virtually all currently recognized organismal phyla. This Superfamily currently (2012) consists of 74 families, each of which is usually concerned with the transport of a certain type of substrate. Many of these families, defined phylogenetically, do not include even a single member that is functionally characterized. In this article, we probe the evolutionary origins of these transporters, providing evidence that they arose from a single 2-transmembrane segment (TMS) hairpin structure that triplicated to give a 6-TMS unit that duplicated to a 12-TMS protein, the most frequent topological type of these permeases. We globally examine MFS protein topologies, focusing on exceptional proteins that deviate from the norm. Nine distantly related families appear to have members with 14 TMSs in which the extra two are usually centrally localized between the two 6-TMS repeat units. They probably have arisen by intragenic duplication of an adjacent hairpin. This alternative topology probably arose multiple times during MFS evolution. Convincing evidence for MFS permeases with fewer than 12 TMSs was not forthcoming, leading to the suggestion that all 12 TMSs are required for optimal function. Some homologs appear to have 13, 14, 15 or 16 TMSs, and the probable locations of the extra TMSs were identified. A few MFS permeases are fused to other functional domains or are fully duplicated to give 24-TMS proteins with dual functions. Finally, the MFS families with no known function were subjected to genomic context analyses leading to functional predictions.
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lysophospholipid flipping across the escherichia coli inner membrane catalyzed by a transporter lplt belonging to the Major Facilitator Superfamily
Journal of Biological Chemistry, 2005Co-Authors: Edgar M Harvat, Yongmei Zhang, Can V Tran, Zhongge Zhang, Matthew W Frank, Charles O Rock, Milton H SaierAbstract:Abstract The transfer of phospholipids across membrane bilayers is protein-mediated, and most of the established transporters catalyze the energy-dependent efflux of phospholipids from cells. This work identifies and characterizes a lysophospholipid transporter gene (lplT, formally ygeD) in Escherichia coli that is an integral component in the 2-acylglycerophosphoethanolamine (2-acyl-GPE) metabolic cycle for membrane protein acylation. The lplT gene is adjacent to and in the same operon as the aas gene, which encodes the bifunctional enzyme 2-acyl-GPE acyltransferase/acyl-acyl carrier protein synthetase. In some bacteria, acyltransferase/acyl-ACP synthetase (Aas) and LplT homologues are fused in a single polypeptide chain. 2-Acyl-GPE transport to the inside of the cell was assessed by measuring the Aas-dependent formation of phosphatidylethanolamine. The Aas-dependent incorporation of [3H]palmitate into phosphatidylethanolamine was significantly diminished in ΔlplT mutants, and the LplT-Aas transport/acylation activity was independent of the proton motive force. The ΔlplT mutants accumulated acyl-GPE in vivo and had a diminished capacity to transport exogenous 2-acylglycerophosphocholine into the cell. Spheroplasts prepared from wild-type E. coli transported and acylated fluorescent 2-acyl-GPE with an apparent Kd of 7.5 μm, whereas this high-affinity process was absent in ΔlplT mutants. Thus, LplT catalyzes the transbilayer movement of lysophospholipids and is the first example of a phospholipid flippase that belongs to the Major Facilitator Superfamily.
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the Major Facilitator Superfamily
Journal of Molecular Microbiology and Biotechnology, 1999Co-Authors: Milton H Saier, J T Beatty, Andre Goffeau, Kevin T Harley, Wilbert Heijne, S C Huang, Donald L Jack, P S Jahn, K Lew, J LiuAbstract:In 1998 we updated earlier descriptions of the largest family of secondary transport carriers found in living organisms, the Major Facilitator Superfamily (MFS). Seventeen families of transport proteins were shown to comprise this Superfamily. We here report expansion of the MFS to include 29 established families as well as five probable families. Structural, functional, and mechanistic features of the constituent permeases are described, and each newly identified family is shown to exhibit specificity for a single class of substrates. Phylogenetic analyses define the evolutionary relationships of the members of each family to each other, and multiple alignments allow definition of family-specific signature sequences as well as all wellconserved sequence motifs. The work described serves to update previous publications and allows extrapolation of structural, functional and mechanistic information obtained with any one member of the Superfamily to other members with limitations determined by the degrees of sequence divergence.
Joanne M Lemieux - One of the best experts on this subject based on the ideXlab platform.
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eukaryotic Major Facilitator Superfamily transporter modeling based on the prokaryotic glpt crystal structure
Molecular Membrane Biology, 2007Co-Authors: Joanne M LemieuxAbstract:The Major Facilitator Superfamily (MFS) of transporters represents the largest family of secondary active transporters and has a diverse range of substrates. With structural information for four MFS transporters, we can see a strong structural commonality suggesting, as predicted, a common architecture for MFS transporters. The rate for crystal structure determination of MFS transporters is slow, making modeling of both prokaryotic and eukaryotic transporters more enticing. In this review, models of eukaryotic transporters Glut1, G6PT, OCT1, OCT2 and Pho84, based on the crystal structures of the prokaryotic GlpT, based on the crystal structure of LacY are discussed. The techniques used to generate the different models are compared. In addition, the validity of these models and the strategy of using prokaryotic crystal structures to model eukaryotic proteins are discussed. For comparison, E. coli GlpT was modeled based on the E. coli LacY structure and compared to the crystal structure of GlpT demonstratin...
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the structural basis of substrate translocation by the escherichia coli glycerol 3 phosphate transporter a member of the Major Facilitator Superfamily
Current Opinion in Structural Biology, 2004Co-Authors: Joanne M Lemieux, Yafei Huang, Daneng WangAbstract:The Major Facilitator Superfamily represents the largest group of secondary active membrane transporters in the cell. The 3.3A resolution structure of a member of this protein Superfamily, the glycerol-3-phosphate transporter from the Escherichia coli inner membrane, reveals two domains connected by a long central loop. These N- and C-terminal domains, each containing a six-helix bundle, are related by pseudo-twofold symmetry. A substrate translocation pore is located between the two domains and is open to the cytoplasm. Two arginines at the closed end of the pore comprise the substrate-binding site. Biochemical experiments show that, upon substrate binding, the protein adopts a more compact conformation. The crystal structure suggests that the transporter operates through a single binding site, alternating access mechanism via a rocker-switch type of movement of the N- and C-terminal domains. The structure and mechanism of the glycerol-3-phosphate transporter form a paradigm for other members of the Major Facilitator Superfamily.
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three dimensional crystallization of the escherichia coli glycerol 3 phosphate transporter a member of the Major Facilitator Superfamily
Protein Science, 2003Co-Authors: Joanne M Lemieux, Manfred Auer, Anthony Villa, Jinmei Song, Myong Jin Kim, Yafei Huang, Daneng WangAbstract:Here we report the successful three-dimensional crystallization of GlpT, the glycerol-3-phosphate transporter from Escherichia coli inner membrane. GlpT possesses 12 transmembrane -helices and is a member of the Major Facilitator Superfamily. It mediates the exchange of glycerol-3-phosphate for inorganic phosphate across the membrane. Approximately 20 phospholipid molecules per protein, identified as negatively charged phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin, were required for the monodispersity of purified GlpT. Analytical size-exclusion chromatography proved to be efficient in identifying detergents for GlpT monodispersity. Nine such detergents were later used for GlpT crystallization. Screening for crystal nucleation was carried out with a variety of polyethylene glycols as the precipitant over a wide pH range. Subsequent identification of a rigid protein core by limited proteolysis and mass spectroscopy resulted in better-ordered crystals. These crystals exhibited orde rt o 3.7A resolution in two dimensions. However, the stacking in the third dimension was partially disordered. This stacking problem was overcome by using a detergent mixture and manipulating the ionic interactions in the crystallization solution. The resulting GlpT crystals diffracted isotropically to 3.3 A resolution and were suitable for structure determination by X-ray crystallography.
Sanath Kumar - One of the best experts on this subject based on the ideXlab platform.
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functional and structural roles of the Major Facilitator Superfamily bacterial multidrug efflux pumps
Microorganisms, 2020Co-Authors: Sanath Kumar, Manjusha Lekshmi, Ammini Parvathi, Manisha Ojha, Nicholas Wenzel, Manuel F. VarelaAbstract: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.
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modulation of antimicrobial efflux pumps of the Major Facilitator Superfamily in staphylococcus aureus
microbiology 2018 Vol. 4 Pages 1-18, 2018Co-Authors: Manjusha Lekshmi, Sanath Kumar, Ugina Shrestha, Parvathi Ammini, Jones Adjei, Leslie M Sanford, Manuel F. VarelaAbstract:Variants of the microorganism Staphylococcus aureus which are resistant to antimicrobial agents exist as causative agents of serious infectious disease and constitute a considerable public health concern. One of the main antimicrobial resistance mechanisms harbored by S. aureus pathogens is exemplified by integral membrane transport systems that actively remove antimicrobial agents from bacteria where the cytoplasmic drug targets reside, thus allowing the bacteria to survive and grow. An important class of solute transporter proteins, called the Major Facilitator Superfamily, includes related and homologous passive and secondary active transport systems, many of which are antimicrobial efflux pumps. Transporters of the Major Facilitator Superfamily, which confer antimicrobial efflux and bacterial resistance in S. aureus, are good targets for development of resistance-modifying agents, such as efflux pump inhibition. Such modulatory action upon these antimicrobial efflux systems of the Major Facilitator Superfamily in S. aureus may circumvent resistance and restore the clinical efficacy of therapy towards S. aureus infection.
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Bacterial Multidrug Efflux Pumps of the Major Facilitator Superfamily as Targets for Modulation
Infectious disorders drug targets, 2016Co-Authors: Sanath Kumar, Gui-xin He, Prathusha Kakarla, Ugina Shrestha, Ranjana Kc, Indrika Ranaweera, T. Mark Willmon, Sharla R. Barr, Alberto J. Hernandez, Manuel F. VarelaAbstract:Abstract Causative agents of infectious disease that are multidrug resistant bacterial pathogens represent a serious public health concern due to the increasingly difficult nature of achieving efficacious clinical treatments. Of the various acquired and intrinsic antimicrobial agent resistance determinants, integral-membrane multidrug efflux pumps of the Major Facilitator Superfamily constitute a Major mechanism of bacterial resistance. The Major Facilitator Superfamily (MFS) encompasses thousands of known related secondary active and passive solute transporters, including multidrug efflux pumps, from bacteria to humans. This review article addresses recent developments involving the targeting by various modulators of bacterial multidrug efflux pumps from the Major Facilitator Superfamily. It is currently of tremendous interest to modulate bacterial multidrug efflux pumps in order to eventually restore the clinical efficacy of therapeutic agents against recalcitrant bacterial infections. Such MFS multidrug efflux pumps are good targets for modulation.
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modulation of bacterial multidrug resistance efflux pumps of the Major Facilitator Superfamily
International Journal of Bacteriology, 2013Co-Authors: Sanath Kumar, Munmun Mukherjee, Manuel F. VarelaAbstract: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.
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lmrs is a multidrug efflux pump of the Major Facilitator Superfamily from staphylococcus aureus
Antimicrobial Agents and Chemotherapy, 2010Co-Authors: Jody L Floyd, Sanath Kumar, Kenneth P Smith, Jared T Floyd, Manuel F. VarelaAbstract:A multidrug efflux pump designated LmrS (lincomycin resistance protein of Staphylococcus aureus), belonging to the Major Facilitator Superfamily (MFS) of transporters, was cloned, and the role of LmrS in antimicrobial efflux was evaluated. The highest relative increase in MIC, 16-fold, was observed for linezolid and tetraphenylphosphonium chloride (TPCL), followed by an 8-fold increase for sodium dodecyl sulfate (SDS), trimethoprim, and chloramphenicol. LmrS has 14 predicted membrane-spanning domains and is homologous to putative lincomycin resistance proteins of Bacillus spp., Lactobacillus spp., and Listeria spp.
