Multidrug efflux transporters in the MATE family

Kuroda, Teruo; Tsuchiya, Tomofusa

doi:10.1016/j.bbapap.2008.11.012

Cited by 333 publications

(236 citation statements)

References 48 publications

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“…Several MATE homologs confer resistance to fluoroquinolones (norfloxacin), cationic dyes (acriflavine and ethidium), and aminoglycosides (e.g., kanamycin and streptomycin) (19). Our data indicate that mmp deletion results in slightly increased susceptibility for several drugs, but its deletion in mutants lacking MSMEG_2619 (efpA) or MSMEG_3563 decreased MIC values further, supporting the importance of M. smegmatis MATE.…”

Section: Discussionsupporting

confidence: 53%

“…Finally, ethidium bromide and norfloxacin were selected for susceptibility testing because both are NorM substrates and EtBr is a preferred DinF substrate (19). Deletion of mmp (mutant LD1184) rendered the strain more susceptible to EtBr (2-fold decrease in MIC) and slightly susceptible for norfloxacin ( Table 2), suggesting that EtBr is a good M. smegmatis MATE substrate and that this protein provides low-level intrinsic resistance for structurally unrelated compounds.…”

Section: Figmentioning

confidence: 99%

“…MATE systems from only a few eukaryotes (26) and prokaryotes (19) have been functionally characterized. The role for most reported prokaryotic MATE transporters is not well defined, since most have been studied by heterologous expression (19).…”

mentioning

confidence: 99%

“…ABC family members are ATP-dependent primary transporters, but the other families are secondary transporters that use an electrochemical transmembrane gradient. MATE proteins (18) have a 12-membrane helix topology and use either H ϩ or Na ϩ gradients to drive efflux (19). In plants, MATE transporters secrete secondary metabolites to defend against microbial pathogens (20,21), and in the liver and kidney they extrude xenobiotic cations (22,23).…”

mentioning

confidence: 99%

“…The role for most reported prokaryotic MATE transporters is not well defined, since most have been studied by heterologous expression (19). To investigate the role of a MATE transporter in Mycobacterium intrinsic resistance, we made an M. smegmatis mutant lacking this protein and characterized it using Phenotype MicroArray (PM).…”

mentioning

confidence: 99%

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Characterization of the MSMEG_2631 Gene ( mmp ) Encoding a Multidrug and Toxic Compound Extrusion (MATE) Family Protein in Mycobacterium smegmatis and Exploration of Its Polyspecific Nature Using Biolog Phenotype MicroArray

Mishra¹,

Daniels²

2013

J Bacteriol

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In Mycobacterium, multidrug efflux pumps can be associated with intrinsic drug resistance. Comparison of putative mycobacterial transport genes revealed a single annotated open reading frame (ORF) for a multidrug and toxic compound extrusion (MATE) family efflux pump in all sequenced mycobacteria except Mycobacterium leprae. Since MATE efflux pumps function as multidrug efflux pumps by conferring resistance to structurally diverse antibiotics and DNA-damaging chemicals, we studied this gene (MSMEG_2631) in M. smegmatis mc 2 155 and determined that it encodes a MATE efflux system that contributes to intrinsic resistance of Mycobacterium. We propose that the MSMEG_2631 gene be named mmp, for mycobacterial MATE protein. Biolog Phenotype MicroArray data indicated that mmp deletion increased susceptibility for phleomycin, bleomycin, capreomycin, amikacin, kanamycin, cetylpyridinium chloride, and several sulfa drugs. MSMEG_2619 (efpA) and MSMEG_3563 mask the effect of mmp deletion due to overlapping efflux capabilities. We present evidence that mmp is a part of an MSMEG_2626-2628-2629-2630-2631 operon regulated by a strong constitutive promoter, initiated from a single transcription start site. All together, our results show that M. smegmatis constitutively encodes an Na ؉ -dependent MATE multidrug efflux pump from mmp in an operon with putative genes encoding proteins for apparently unrelated functions.

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Section: Discussionsupporting

confidence: 53%

Section: Figmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Characterization of the MSMEG_2631 Gene ( mmp ) Encoding a Multidrug and Toxic Compound Extrusion (MATE) Family Protein in Mycobacterium smegmatis and Exploration of Its Polyspecific Nature Using Biolog Phenotype MicroArray

Mishra¹,

Daniels²

2013

J Bacteriol

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Antibiotic Resistance: Mechanisms and Impact

Puglia

Gualerzi

2017

Kirk-Othmer Encyclopedia of Chemical Technology

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Bacterial multidrug resistance poses an enormous threat to the health of mankind and risks to push back the clock of human medicine to the preantibiotic era, when bacterial infections (eg, tuberculosis, syphilis, and staphylococcal infections of wounds) were almost untreatable and resulted in a huge death toll. Bacterial antibiotic resistance (AR) may be conferred by a plethora of mechanisms that can be grouped into three categories: (a) Modification or protection of the antibiotic target—This can occur (i) as a result of one or more mutations of the gene encoding the target (eg, fluoroquinolones resistance due to mutations of topoisomerase II); (ii) following an enzymatic process that chemically modifies structure and properties of the target (eg, macrolide resistance due to 23S rRNA methylation); or (iii) the physical removal of the inhibitor from its target (resistance to tetracycline by the intervention of ribosomal protection proteins). (b) Enzymatic inactivation of the antimicrobial drug (e.g. resistance to β‐lactam antibiotics upon hydrolysis of the β‐lactam ring by β‐lactamases). (c) Blocking the entrance of the antibiotic or promoting its extrusion by remodeling of the cellular membrane (eg, resistance to polymixins) or activation of cellular efflux pumps (eg, multidrug resistance). In this article, we review in some depth all these mechanisms of resistance to various types of antibiotics, describe the concerns of the world health organizations, the likely socioeconomical impact that AR will have in the future, and some possible actions that can be taken to cope with this global problem.

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Crystal structures of a nicotine MATE transporter provide insight into its mechanism of substrate transport

et al. 2021

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A transporter of the multidrug and toxic compound extrusion (MATE) family, Nicotiana tabacum MATE2 (NtMATE2), is located in the vacuole membrane of the tobacco plant root and is involved in the transportation of nicotine, a secondary or specialized metabolic compound in Solanaceae. Here, we report the crystal structures of NtMATE2 in its outward-facing forms. The overall structure has a bilobate V-shape with pseudo-symmetrical assembly of the N-and C-lobes. In one crystal structure, the C-lobe cavity of NtMATE2 interacts with an unidentified molecule that may partially mimic a substrate. In addition, NtMATE2-specific conformational transitions imply that an unprecedented movement of the transmembrane a-helix 7 is related to the release of the substrate into the vacuolar lumen.

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Multidrug efflux transporters in the MATE family

Cited by 333 publications

References 48 publications

Characterization of the MSMEG_2631 Gene ( mmp ) Encoding a Multidrug and Toxic Compound Extrusion (MATE) Family Protein in Mycobacterium smegmatis and Exploration of Its Polyspecific Nature Using Biolog Phenotype MicroArray

Characterization of the MSMEG_2631 Gene ( mmp ) Encoding a Multidrug and Toxic Compound Extrusion (MATE) Family Protein in Mycobacterium smegmatis and Exploration of Its Polyspecific Nature Using Biolog Phenotype MicroArray

Antibiotic Resistance: Mechanisms and Impact

Crystal structures of a nicotine MATE transporter provide insight into its mechanism of substrate transport

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