Efflux pumps

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

Membrane ATPases; Membrane transporters; Outward transporters

Definition
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Efflux pumps are protein systems that take on transporter functions in the wall of bacteria as well as in eukaryotic cells. The term efflux pump is an outdated name for membrane ATPases and membrane transporters that transport molecules out of the cell.

Classification
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Efflux pumps can be divided into 5 large families:

  • the Small Multidrug Resistance (SMR) family
  • the Resistance Nodulation Cell Division (RND) family
  • the ATP-Binding Cassette (ABC) family
  • the Multidrug and Toxic Compound Extrusion (MATE) family
  • the Major Facilitator Superfamily (MFS).

Inhibitors against efflux pumps already exist. However, they cannot be used clinically because they do not only transport antibiotics.

General information
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In the genome of a bacterium there are a large number of genes that code for different transporters (influenx and efflux). For example, 20% of the gene products of lactobacilli have such a transporter function (farm H 2019). The active transport of a substance from the cell, the so-called efflux, plays an important role in antibiotic resistance. Multidrug resistance (MDR) efflux pumps pose a particular problem.

Efflux pumps (membrane transporters) channel a large number of structurally unrelated substrates out of the cell. This also applies to antibiotics that are transported out of the cell before they reach their actual target proteins. Thus, efflux pumps are the cause of an unspecific resistance mechanism. Efflux pumps are also responsible for the antibiotic resistance of bacteria and the resistance of fungi to antimycotics. For example, all proteus bacteria are generally resistant to tetracyclines due to efflux pumps. Some efflux pumps are specialized for certain antibiotics. Remarkably, bacteria can upregulate the expression of certain efflux structures when required.

Note(s)
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For example, the genes of the individual ABC transporters are designated with a capital letter and a number. Z. B. ABCB1 encodes the "permeability glycoprotein" P-gp. ABC transporters were first recognised as resistance factors of chemotherapeutic drugs (cytostatics) and often have corresponding synonyms such as MDR1 (multiple drug resistance protein 1). Since transporters are often expressed on the apical (outwardly directed) side of the cell membrane, they have also been assigned CD numbers, e.g.  B. CD243 for P-gp (CD = cluster of differentiation, refers to surface proteins of cells). Drugs that have entered a tumour cell can be transported out of the cell by transporters, which is known as chemoresistance of the tumour.

Literature
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  1. Court H (2019). Basic principles of antibacterial chemotherapy. In: Hof H, Schlüter D, Dörries R, ed. Duale Reihe Medizinische Mikrobiologie. 7th, completely revised and extended edition. Stuttgart: Thieme S 311-313

Outgoing links (1)

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Last updated on: 29.10.2020