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Encyclopedia > Efflux

Active efflux is a mechanism responsible for extrusion of toxic substances and antibiotics outside the cell. Its importance lies in its contribution to bacterial antimicrobial resistance. Efflux systems function via an energy-dependent mechanism (Active transport) to pump out unwanted toxic substances through specific efflux pumps. Some efflux systems are drug-specific while others may accommodate multiple drugs and thus contribute significantly to bacterial multidrug resistance (MDR). An antibiotic is a drug that kills or slows the growth of bacteria. ... This article or section does not cite its references or sources. ...

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Efflux in bacteria

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Bacterial efflux pumps

Efflux pumps are proteinaceous transporters localized in the cytoplasmic membrane of all kind of cells. They are active transporters meaning that they require a source of chemical energy to perform their function. Some are primary active transporters utilizing Adenosine triphosphate hydrolysis as a source of energy, while others are secondary active transporters (uniporters, symporters or antiporters) in which transport is coupled to an electrochemical potential difference created by pumping out hydrogen or sodium ions outside the cell.
Bacterial efflux transporters are classified into five major superfamilies, based on the amino acid sequence and the energy source used to export their substrates: A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... Drawing of a cell membrane A component of every biological cell, the cell membrane (or plasma membrane) is a thin and structured bilayer of phospholipid and protein molecules that encapsulate the cell. ... This article or section does not cite its references or sources. ... This article or section does not cite its references or sources. ... Adenosine 5-triphosphate (ATP), discovered in 1929 by Karl Lohmann,[1] is a multifunctional nucleotide primarily known in biochemistry as the molecular currency of intracellular energy transfer. ... This article or section does not cite its references or sources. ... A uniporter is an Integral Membrane Protein that is involved in facilitated diffusion. ... A symporter, also known as a coporter, is an integral membrane protein that is involved in facilitated diffusion. ... An antiporter is an integral membrane protein that is involved in secondary active transport. ... Electrochemical potential is a thermodynamic measure that reflects energy from entropy and electrostatics and is typically invoked in molecular processes that involve diffusion. ... General Name, Symbol, Number hydrogen, H, 1 Chemical series nonmetals Group, Period, Block 1, 1, s Appearance colorless Atomic mass 1. ... General Name, Symbol, Number sodium, Na, 11 Chemical series alkali metals Group, Period, Block 1, 3, s Appearance silvery white Atomic mass 22. ... ... An amino acid residue is what is left of an amino acid once a molecule of water has been lost (an H+ from the nitrogenous side and an OH- from the carboxylic side) in the formation of a peptide bond. ... Peptide sequence or amino acid sequence is the order in which amino acid residues, connected by peptide bonds, lie in the chain. ...

  1. The major facilitator superfamily (MFS);
  2. The ATP-binding cassette superfamily (ABC);
  3. The small multidrug resistance family (SMR);
  4. The resistance-nodulation-cell division superfamily (RND); and
  5. The multidrug and toxic compound extrusion family (MATE).

Of these only the ABC superfamily are primary transporters, the rest being secondary transporters utilizing proton or sodium gradient as a source of energy. While MFS dominates in Gram positive bacteria , the RND family is unique to Gram-negatives. Adenosine 5-triphosphate (ATP), discovered in 1929 by Karl Lohmann,[1] is a multifunctional nucleotide primarily known in biochemistry as the molecular currency of intracellular energy transfer. ... Properties [1][2] In physics, the proton (Greek proton = first) is a subatomic particle with an electric charge of one positive fundamental unit (1. ... An ion gradient is a concentration gradient of ions, it can be called an electrochemical potential gradient of ions across membranes. ... Gram-positive bacteria are those that are stained dark blue or violet by gram staining, in contrast to gram-negative bacteria, which are not affected by the stain. ... Bacteria that are Gram-negative are not stained dark blue or violet by Gram staining, in contrast to Gram-positive bacteria. ...

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Function

Although antibiotics are the most clinically important substrates of efflux systems, it is probable that most efflux pumps have other natural physiological functions. Examples include:

  • The E.coli AcrAB efflux system which has a physiologic role of pumping out bile acids and fatty acids to lower their toxicity.
  • The MFS family Ptr pump in Streptomyces pristinaespiralis appears to be an autoimmunity pump for this organism when it turns on production of pristinamycins I and II.
  • The AcrAB–TolC system in E.coli is suspected to have a role in the transport of the calcium-channel components in the E. coli membrane.
  • The MtrCDE system plays a protective role by providing resistance to faecal lipids in rectal isolates of Neisseria gonorrhoeae.
  • The AcrAB efflux system of Erwinia amylovora is important for this organism's virulence, plant (host) colonization and resistance to plant toxins.

The ability of efflux systems to recognize a large number of compounds other than their natural substrates is probably because substrate recognition is based on physicochemical properties, such as hydrophobicity, aromaticity and ionizable character rather than on defined chemical properties, as in classical enzyme-substrate or ligand-receptor recognition. Because most antibiotics are amphiphilic molecules - possessing both hydrophilic and hydrophobic characters, they are easily recognized by many efflux pumps. Binomial name Escherichia coli T. Escherich, 1885 E. coli at 10,000x magnification Escherichia coli (usually abbreviated to E. coli) is one of the main species of bacteria that live in the lower intestines of warm-blooded animals (including birds and mammals) and are necessary for the proper digestion of... Autoimmunity is the failure of an organism to recognise its own constituent parts (down to the sub-molecular levels) as Self, which results in an immune response against its own cells and tissues. ... Binomial name Neisseria gonorrhoeae Zopf, 1885 Neisseria gonorrhoeae is a species of Gram-negative (see also Gram Stain) bacteria responsible for the disease gonorrhoea. ... Virulence is a term used to refer to either the relative pathogenicity or the relative ability to do damage to the host of an infectious agent. ... In chemistry, hydrophobic or lipophilic species, or hydrophobes, tend to be electrically neutral and nonpolar, and thus prefer other neutral and nonpolar solvents or molecular environments. ... Aromaticity is a chemical property in which a conjugated ring of unsaturated bonds, lone pairs, or empty orbitals exhibit a stabilization stronger than would be expected by the stabilization of conjugation alone. ... ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... In biochemistry, a substrate is a molecule which is acted upon by an enzyme. ... It has been suggested that this article or section be merged with ligand. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... An amphipathic (a. ...

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Impact on antimicrobial resistance

The impact of efflux mechanisms on antimicrobial resistance is large, this is usually attributed to the following:

  • The genetic elements encoding efflux pumps may be encoded on chromosomes and/or plasmids, thus contributing to both intrinsic (natural) and acquired resistance respectively. As an intrinsic mechanism of resistance, efflux pump genes can survive a hostile environment ( for example in the presence of antibiotics) which allows for the selection of mutants that over-express these genes. Being located on transpoable genetic elements as plasmids or transposons is also advantageous for the microorganisms as it allows for the easy spread of efflux genes between distant species.
  • Antibiotics can act as inducers and regulators of the expression of some efflux pumps.
  • Expression of several efflux pumps in a given bacterial species may lead to a broad spectrum of resistance when considering the shared substrates of some multi-drug efflux pumps, where one efflux pump may confer resistance to a wide range of antimicrobials.
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This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... Figure 1: Chromosome. ... Figure 1 : Schematic drawing of a bacterium with plasmids enclosed. ... A mutant (also known to early geneticists as a monster) is an individual, organism, or new genetic character arising or resulting from an instance of mutation, which is a sudden structural change within the DNA of a gene or chromosome of an organism resulting in the creation of a new... Gene expression, also called protein expression or often simply expression is the process by which a genes DNA sequence is converted into the structures and functions of a cell. ... Figure 1 : Schematic drawing of a bacterium with plasmids enclosed. ... Transposons are sequences of DNA that can move around to different positions within the genome of a single cell, a process called transposition. ... Gene expression, also called protein expression or often simply expression is the process by which a genes DNA sequence is converted into the structures and functions of a cell. ...

Efflux in eukaryotes

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Efflux inhibitors

Several trials are currently being conducted to develop drugs that can be co-administered with antibiotics to act as inhibitors for the efflux-mediated extrusion of antibiotics. None of the efflux inhibitors tested is yet in clinical use. However, some of them are used to determine the efflux prevalence in clinical isolates.

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See also


  Results from FactBites:
 
Measuring soil efflux of volcanic gases--a volcano gas monitoring technique (499 words)
Soil efflux measurements can be made in areas where volcanic gases, typically CO, rise from depth and discharge into the soil just beneath the surface.
The rate of increase of CO in the chamber is then used along with ambient temperature, pressure, and other parameters to calculate a soil CO efflux for that location.
Gerlach, T.M., Doukas, M.P., McGee, K.A., and Kessler, R., 2000, Soil efflux and totatl emission rates of magmatic CO at the Horseshoe Lake tree kill, Mammoth Mountain, California, 1995-1999: Chemical Geology, (in press).
Antibiotic efflux mechanisms (1210 words)
Efflux from bacteria: antibiotic efflux pumps are nowadays believed to significantly contribute to acquired bacterial resistance because of the very broad variety of substrates they recognize, their expression in important pathogens, and their cooperation with other mechanisms of resistance.
In this context, we examine which antibiotics are subject to active efflux in phagocytic cells and try to identify at the phenotypic and genotypic levels the transporters involved (Figures 2 and 3).
Influence of P-glycoprotein and MRP efflux pump inhibitors on the intracellular activity of azithromycin and ciprofloxacin in macrophages infected by Listeria monocytogenes or Staphylococcus aureus.
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