Etymologyeffluere: to flow.
- The process of flowing out.
- We all age through the efflux of time.
- The efflux of matter from a boil can be painful.
- That which has flowed out.
- The efflux of a boil is yuk!
- Russian: сопло (sopló)
- To run out.
- When three years efflux, the claim will have prescribed.
- To flow forth.
- To pass away.
Active efflux is a mechanism responsible for extrusion of toxic substances and antibiotics outside the cell, this is considered to be a vital part of xenobiotic metabolism. This mechanism is important in medicine as it can contribute to bacterial antibiotic 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 to bacterial multidrug resistance (MDR).
Efflux in bacteria
Bacterial efflux pumpsEfflux pumps are proteinaceous transporters localized in the cytoplasmic membrane of all kinds 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:
- The major facilitator superfamily (MFS);
- The ATP-binding cassette superfamily (ABC);
- The small multidrug resistance family (SMR);
- The resistance-nodulation-cell division superfamily (RND); and
- The multidrug and toxic compound extrusion family (MATE).
FunctionAlthough 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.
Impact on antimicrobial resistanceThe 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.
Efflux in eukaryotes
In eukaryotic cells, the existence of efflux pumps has been known since the discovery of p-glycoprotein in 1976 by Juliano and Ling. Efflux pumps are one of the major causes of anticancer drug resistance in eukaryotic cells. These include monocarboxylate transporter (MCT), organic anion transporter (OAT), multiple drug resistance (MDR)- also referred as p-glycoprotein, multidrug resistance-associated protein (MRP), peptide transporter (PEPT), Na+ phosphate transporter (NPT) and organic cation transporter (OCT). These transporters are distributed all along the kidney, intestine, liver and brain cells.
Efflux inhibitorsSeveral 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. Its shown that Verapamil can inhibit P-glycoprotein mediated efflux which can increase oral absorption of some compounds.
efflux in Dutch: Efflux