ATP-binding Cassette Transporter - ABC Exporters

ABC Exporters

Prokaryotic ABC exporters are abundant and have close homologues in eukaryotes. This class of transporters is studied based on the type of substrate that is transported. One class is involved in the protein (e.g. toxins, hydrolytic enzymes, S-layer proteins, lantibiotics, bacteriocins, and competence factors) export and the other in drug efflux. ABC transporters have gained extensive attention because they contribute to the resistance of cells to antibiotics and anticancer agents by pumping drugs out of the cells.

In gram-negative organisms, ABC transporters mediate secretion of protein substrates across inner and outer membranes simultaneously without passing through the periplasm. This type of secretion is referred to as type I secretion, which involves three components that function in concert: an ABC exporter, a membrane fusion protein (MFP), and an outer membrane factor (OMF). An example is the secretion of hemolysin (HlyA) from E. coli where the inner membrane ABC transporter HlyB interacts with an inner membrane fusion protein HlyD and an outer membrane facilitator TolC. TolC allows hemolysin to be transported across the two membranes, bypassing the periplasm.

Bacterial drug resistance has become an increasingly major health problem. One of the mechanisms for drug resistance is associated with an increase in antibiotic efflux from the bacterial cell. Drug resistance associated with drug efflux, mediated by P-glycoprotein, was originally reported in mammalian cells. In bacteria, Levy and colleagues presented the first evidence that antibiotic resistance was caused by active efflux of a drug. P-glycoprotein is the best-studied efflux pump and as such has offered important insights into the mechanism of bacterial pumps. Although some exporters transport a specific type of substrate, most transporters extrude a diverse class of drugs with varying structure. These transporters are commonly called multi-drug resistant (MDR) ABC transporters and sometimes referred to as "hydrophobic vacuum cleaners".