Efflux Pumps
One-Sentence Definition
Efflux pumps are membrane transport proteins that actively expel antibiotics, biocides, and dyes from the bacterial cell, lowering intracellular drug concentration.
Simple Explanation
The cell throws the drug back out faster than it comes in.
Detailed Scientific Explanation
Families: RND (dominant in Gram-negatives), MFS, ABC, SMR, MATE.
Gram-negative RND pumps are tripartite: inner-membrane transporter + periplasmic adaptor + outer-membrane channel, spanning the whole envelope. Canonical examples: AcrAB-TolC (Escherichia coli, Klebsiella pneumoniae) and MexAB-OprM (Pseudomonas aeruginosa).
Why they matter more than their raw MIC effect suggests
- Broad substrate range → simultaneous multidrug phenotype
- Usually regulated, not acquired: mutations in local or global repressors (acrR, marR, mexR) cause overexpression
- Because the change is in expression, gene-detection tools miss it entirely (Genotype to Phenotype Prediction)
- They lower drug concentration enough to let target mutations accumulate — a stepping stone to high-level resistance
- Also export biocides and bile salts, so disinfectant use can co-select
Mechanism
Proton-motive-force-driven antiport (RND, MFS, SMR, MATE) or ATP hydrolysis (ABC) moves substrate from the cytoplasm or periplasm to the exterior.
Clinical Importance
- Contributes to MDR phenotypes in ESKAPE Pathogens, particularly P. aeruginosa and Acinetobacter
- Efflux-pump inhibitors remain experimental; toxicity has blocked clinical translation
Research Importance
- Structural work on RND pumps guides inhibitor design (Structural Bioinformatics)
Diagnostic Relevance
- Suspected when MICs rise across unrelated drug classes without any acquired gene
AMR Relevance
One of the five mechanisms in Mechanisms of Antibiotic Resistance; a leading reason genomic prediction underperforms.
Related MOCs
Active Recall Questions
- Why are RND pumps tripartite in Gram-negatives?
- Why does a resistance-gene database miss efflux-mediated resistance?
- How can disinfectant use select for antibiotic resistance?