Multi-antimicrobial Extrusion Protein
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Multi-antimicrobial Extrusion Protein
Multi-antimicrobial extrusion protein (MATE) also known as multidrug and toxin extrusion or multidrug and toxic compound extrusion is a family of proteins which function as drug/sodium or proton antiporters. Function The MATE proteins in bacteria, archaea and eukaryotes function as fundamental transporters of metabolic and xenobiotic organic cations. Structure These proteins are predicted to have 12 alpha-helical transmembrane regions, some of the animal proteins may have an additional C-terminal helix. The X-ray structure of the NorM was determined to 3.65 Å, revealing an outward-facing conformation with two portals open to the outer leaflet of the membrane and a unique topology of the predicted 12 transmembrane helices distinct from any other known multidrug resistance transporter. Discovery The multidrug efflux transporter NorM from '' V. parahaemolyticus'' which mediates resistance to multiple antimicrobial agents (norfloxacin, kanamycin, ethidium bromide etc. ...
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Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residue ...
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Norfloxacin
Norfloxacin, sold under the brand name Noroxin among others, is an antibiotic that belongs to the class of fluoroquinolone antibiotics. It is used to treat urinary tract infections, gynecological infections, inflammation of the prostate gland, gonorrhea and bladder infection. Eye drops were approved for use in children older than one year of age. Norfloxacin is associated with a number of rare serious adverse reactions as well as spontaneous tendon ruptures and irreversible peripheral neuropathy. Tendon problems may manifest long after therapy had been completed and in severe cases may result in lifelong disabilities. It was patented in 1977 and approved for medical use in 1983. Medical uses The initial approval by the U.S. Food and Drug Administration (FDA) in 1986 encompassed the following indications: *Uncomplicated urinary tract infections (including cystitis) *Complicated urinary tract infections (restricted use) *Uncomplicated urethral and cervical gonorrhea (''howeve ...
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Resistance-Nodulation-Cell Division Superfamily (RND)
Resistance-nodulation-division (RND) family transporters are a category of bacterial efflux pumps, especially identified in Gram-negative bacteria and located in the cytoplasmic membrane, that actively transport substrates. The RND superfamily includes seven families: the heavy metal efflux (HME), the hydrophobe/amphiphile efflux-1 (gram-negative bacteria), the nodulation factor exporter family (NFE), the SecDF protein-secretion accessory protein family, the hydrophobe/amphiphile efflux-2 family, the eukaryotic sterol homeostasis family, and the hydrophobe/amphiphile efflux-3 family. These RND systems are involved in maintaining homeostasis of the cell, removal of toxic compounds, and export of virulence determinants. They have a broad substrate spectrum and can lead to the diminished activity of unrelated drug classes if over-expressed. The first reports of drug resistant bacterial infections were reported in the 1940s after the first mass production of antibiotics. Most of the ...
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SLC47A2
Multidrug and toxin extrusion protein 2 is a protein which in humans is encoded by the ''SLC47A2'' gene. Function This gene encodes a protein belonging to a family of transporters involved in excretion of toxic electrolytes, both endogenous and exogenous, through urine and bile. This transporter family shares homology with the bacterial MATE (multi antimicrobial extrusion protein or multidrug and toxic compound extrusion) protein family responsible for drug resistance. This gene is one of two members of the MATE transporter family located near each other on chromosome 17. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. Discovery The multidrug efflux transporter NorM from '' V. parahaemolyticus'' which mediates resistance to multiple antimicrobial agents (norfloxacin, kanamycin, ethidium bromide etc.) and its homologue from ''E. coli'' were identified in 1998. NorM seems to function as drug/sodium antiporter An ant ...
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SLC47A1
Multidrug and toxin extrusion protein 1 (MATE1), also known as solute carrier family 47 member 1, is a protein that in humans is encoded by the ''SLC47A1'' gene. SLC47A1 belongs to the MATE (multidrug and toxic compound extrusion) family of transporters that are found in bacteria, archaea and eukaryotes. Gene The ''SLC47A1'' gene is located within the Smith–Magenis syndrome region on chromosome 17. Function SLC47A1 is a member of the MATE family of transporters that excrete endogenous and exogenous toxic electrolytes through urine and bile. Discovery The multidrug efflux transporter NorM from '' V. parahaemolyticus'' which mediates resistance to multiple antimicrobial agents (norfloxacin, kanamycin, ethidium bromide etc.) and its homologue from ''E. coli'' were identified in 1998, which is the first of Solute carrier family 47 member. NorM seems to function as drug/sodium antiporter which is the first example of Na+-coupled multidrug efflux transporter. NorM is a p ...
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Escherichia Coli
''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escherichia'' that is commonly found in the lower intestine of warm-blooded organisms. Most ''E. coli'' strains are harmless, but some serotypes ( EPEC, ETEC etc.) can cause serious food poisoning in their hosts, and are occasionally responsible for food contamination incidents that prompt product recalls. Most strains do not cause disease in humans and are part of the normal microbiota of the gut; such strains are harmless or even beneficial to humans (although these strains tend to be less studied than the pathogenic ones). For example, some strains of ''E. coli'' benefit their hosts by producing vitamin K2 or by preventing the colonization of the intestine by pathogenic bacteria. These mutually beneficial relationships between ''E. col ...
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Ethidium Bromide
Ethidium bromide (or homidium bromide, chloride salt homidium chloride) is an intercalating agent commonly used as a fluorescent tag (nucleic acid stain) in molecular biology laboratories for techniques such as agarose gel electrophoresis. It is commonly abbreviated as EtBr, which is also an abbreviation for bromoethane. To avoid confusion, some laboratories have used the abbreviation EthBr for this salt. When exposed to ultraviolet light, it will fluoresce with an orange colour, intensifying almost 20-fold after binding to DNA. Under the name homidium, it has been commonly used since the 1950s in veterinary medicine to treat trypanosomiasis in cattle. The high incidence of antimicrobial resistance makes this treatment impractical in some areas, where the related isometamidium chloride is used instead. Despite its reputation as a mutagen, it is relatively safe to handle. Structure, chemistry, and fluorescence As with most fluorescent compounds, ethidium bromide is aromatic. ...
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Kanamycin
Kanamycin A, often referred to simply as kanamycin, is an antibiotic used to treat severe bacterial infections and tuberculosis. It is not a first line treatment. It is used by mouth, injection into a vein, or injection into a muscle. Kanamycin is recommended for short-term use only, usually from 7 to 10 days. As with most antibiotics, it is ineffective in viral infections. Common side effects include hearing and balance problems. Kidney problems may also occur. Kanamycin is not recommended during pregnancy as it may harm the baby. It is likely safe during breastfeeding. Kanamycin is in the aminoglycoside family of medications. It works by blocking the production of proteins that are required for bacterial survival. Kanamycin was first isolated in 1957 by Hamao Umezawa from the bacterium ''Streptomyces kanamyceticus''. It was removed from the World Health Organization's List of Essential Medicines in 2019. It is no longer marketed in the United States. Medical uses Spectrum ...
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Vibrio Parahaemolyticus
''Vibrio parahaemolyticus'' (V. parahaemolyticus) is a curved, rod-shaped, Gram-negative bacterium found in the sea and in estuaries which, when ingested, may cause gastrointestinal illness in humans. ''V. parahaemolyticus'' is oxidase positive, facultatively aerobic, and does not form spores. Like other members of the genus ''Vibrio'', this species is motile, with a single, polar flagellum. Pathogenesis While infection can occur by the fecal-oral route, ingestion of bacteria in raw or undercooked seafood, usually oysters, is the predominant cause of the acute gastroenteritis caused by ''V. parahaemolyticus''. Wound infections also occur, but are less common than seafood-borne disease. The disease mechanism of ''V. parahaemolyticus'' infections has not been fully elucidated. Clinical isolates usually possess a pathogenicity island (PAI) on the second chromosome. The PAI can be acquired by horizontal gene transfer and contains genes for several virulence factors. Two fully s ...
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Antiporter
An antiporter (also called exchanger or counter-transporter) is a cotransporter and integral membrane protein involved in secondary active transport of two or more different molecules or ions across a phospholipid membrane such as the plasma membrane in opposite directions, one into the cell and one out of the cell. Na+/H+ antiporters have been reviewed. In secondary active transport, one species of solute moves along its electrochemical gradient, allowing a different species to move against its own electrochemical gradient. This movement is in contrast to primary active transport, in which all solutes are moved against their concentration gradients, fueled by ATP. Transport may involve one or more of each type of solute. For example, the Na+/Ca2+ exchanger, found in the plasma membrane of many cells, moves three sodium ions in one direction, and one calcium ion in the other. Role in Homeostatic Mechanisms Na+/H+ Antiporters Antiporters, such as Na+/H+ antiporter protei ...
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Membrane Transport Protein
A membrane transport protein (or simply transporter) is a membrane protein involved in the movement of ions, small molecules, and macromolecules, such as another protein, across a biological membrane. Transport proteins are integral transmembrane proteins; that is they exist permanently within and span the membrane across which they transport substances. The proteins may assist in the movement of substances by facilitated diffusion or active transport. The two main types of proteins involved in such transport are broadly categorized as either ''channels'' or ''carriers''. The solute carriers and atypical SLCs are secondary active or facilitative transporters in humans. Collectively membrane transporters and channels are known as the transportome. Transportomes govern cellular influx and efflux of not only ions and nutrients but drugs as well. Difference between channels and carriers A carrier is not open simultaneously to both the extracellular and intracellular environments. ...
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