Chapter

Bacterial antimicrobial efflux pumps of the MFS and MATE transporter families: A review

In book: Recent Research Developments in Antimicrobial Agents & Chemotherapy, Chapter: Bacterial antimicrobial efflux pumps of the MFS and MATE transporter families: A review., Publisher: Research Signpost, Inc., Editors: Shankar Pandali, pp.1-21

ABSTRACT

Bacteria are causative agents of human infectious
disease and are a serious public health concern due to drug and
multi-drug resistance determinants that reduce the clinical efficacy
of antimicrobial agents. Among the variety of antimicrobial
resistance mechanisms, drug and multi-drug efflux pumps
represent a significant cause of chemotherapeutic failure in the
treatment efforts of bacterial infectious disease. This chapter deals
mainly with bacterial drug and multi-drug efflux pump systems of
the major facilitator superfamily (MFS) and multi-drug and toxic
compound extrusion (MATE) family. Studies of these bacterial
anti-bacterial drug efflux systems will help our understanding of
their molecular mechanisms and may help reduce the conditions
that foster multi-drug resistance.

    • "The second pump system, called secondary active transport, uses the energy stored in the form of ion gradients to actively extrude drugs from the cells of bacteria [9]. Within the class of secondary active transporters, several important pump families are known; they include the resistance nodulation cell division (RND) superfamily [10], the small multidrug resistance (SMR) superfamily [11], the multidrug and toxic compound extrusion (MATE) superfamily [12] [13], and the major facilitator superfamily (MFS) [14] [15]. This review will focus on the MFS pumps as potential targets for modulation. "
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    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 of tremendous interest to modulate bacterial multidrug efflux pumps in order to eventually restore the clinical efficacy of recalcitrant bacterial infections. Such MFS multidrug efflux pumps are good targets for modulation.
    No preview · Article · Jan 2016
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    • "We observed the repression of genes encoding ABC membrane transporters involved in multidrug resistance (MDR) pumps, such as MatE and MdtK which belong to the MATE-family transporters for multidrug and toxic compound extrusion (Omote et al. 2006), and also the repression of genes encoding transporters from the major facilitator superfamily (MFS) (Lubelski et al. 2007; Kumar et al. 2013). MDR pumps are capable of extruding heavy metals (Silver and Phung 2005; Martínez et al. 2009). "
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    ABSTRACT: The molecular response of Pseudomonas fluorescens cells exposed to a mixture of heavy metals remains largely unknown. Here, we studied the temporal changes in the early gene expression of P. fluorescens cells exposed to three doses of a polymetallic solution over two exposure times, through the application of a customized cDNA microarray. At the lowest metal dose (MD/4), we observed a repression of the Hsp70 chaperone system, MATE and MFS transporters, TonB membrane transporter and histidine kinases, together with an overexpression of metal transport (ChaC, CopC), chemotaxis and glutamine synthetase genes. At the intermediate metal dose (MD), several amino acid transporters, a response regulator (CheY), a TonB-dependent receptor and the mutT DNA repair gene were repressed; by contrast, an overexpression of genes associated with the antioxidative stress system and the transport of chelates and sulfur was observed. Finally, at the highest metal dose (4MD), a repression of genes encoding metal ion transporters, drug resistance and alginate biosynthesis was found, together with an overexpression of genes encoding antioxidative proteins, membrane transporters, ribosomal proteins, chaperones and proteases. It was concluded that P. fluorescens cells showed, over exposure time, a highly complex molecular response when exposed to a polymetallic solution, involving mechanisms related with chemotaxis, signal transmission, membrane transport, cellular redox state, and the regulation of transcription and ribosomal activity.
    Full-text · Article · Mar 2015 · Cell Biology and Toxicology
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    ABSTRACT: Pathogenic strains of Vibrio cholerae are responsible for endemic and pandemic outbreaks of the disease cholera. The complete toxigenic mechanisms underlying virulence in Vibrio strains are poorly understood. The hypothesis of this work was that virulent versus non-virulent strains of V. cholerae harbor distinctive genomic elements that encode virulence. The purpose of this study was to elucidate genomic differences between the O1 serotypes and non-O1 V. cholerae PS15, a non-toxigenic strain, in order to identify novel genes potentially responsible for virulence. In this study, we compared the whole genome of the non-O1 PS15 strain to the whole genomes of toxigenic serotypes at the phylogenetic level, and found that the PS15 genome was distantly related to those of toxigenic V. cholerae. Thus we focused on a detailed gene comparison between PS15 and the distantly related O1 V. cholerae N16961. Based on sequence alignment we tentatively assigned chromosome numbers 1 and 2 to elements within the genome of non-O1 V. cholerae PS15. Further, we found that PS15 and O1 V. cholerae N16961 shared 98% identity and 766 genes, but of the genes present in N16961 that were missing in the non-O1 V. cholerae PS15 genome, 56 were predicted to encode not only for virulence-related genes (colonization, antimicrobial resistance, and regulation of persister cells) but also genes involved in the metabolic biosynthesis of lipids, nucleosides and sulfur compounds. Additionally, we found 113 genes unique to PS15 that were predicted to encode other properties related to virulence, disease, defense, membrane transport, and DNA metabolism. Here, we identified distinctive and novel genomic elements between O1 and non-O1 V. cholerae genomes as potential virulence factors and, thus, targets for future therapeutics. Modulation of such novel targets may eventually enhance eradication efforts of endemic and pandemic disease cholera in afflicted nations.
    Full-text · Article · Jun 2014
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