AcrB is one of the many important multi-drug transporters found in a Gram-negative bacteria such as E. coli. The primary function of AcrB is to allow Gram-negative bacteria to exhibit tolerance towards antibiotic drugs; a multiple number of them. We are beginning to understand how this ability to recognise many different drugs is expressed by AcrB. Here, we will explore this ability using the basis of molecular weight differentiation used by AcrB in recognising the antibiotic drugs and transporting them out of the cell.
In previous studies performed with AcrB, low molecular weight drugs such as minocycline & doxorubicin have been shown to bind to a specific phenylalanine cluster region (the distal pocket) of the binding monomer of AcrB. Further analysis revealed the drugs were exported out of the E. coli via a 3-step functionally rotating mechanism (which we shall look at later).
The latest studies involving the broad specificity range of AcrB has revealed an additional binding pocket in the access monomer of the exporter molecule which is suspected to bind high molecular weight drugs such as rifampicin and erythromycin. It is this additional binding site that will be the key focus of our analysis of AcrB as we compare it to the previously studied distal pocket binding site.
A brief preview of the AcrB multi-drug exporter:
- A homotrimer component of a tripartite complex - with the AcrA membrane fusion protein which connects AcrB to TolC, the outer membrane channel which allows drugs to bypass the outer membrane barrier of bacteria and straight into the external medium.
- Tripartite system is also know as the Efflux pump complex which may be energy dependent to perform its functions.
- Previous experiment with deletion of genes encoding for one or many components of the AcrB-AcrA-TolC tripartite system showed increased antibiotic susceptibility in E. coli.
This video here illustrates the basic principles behind the efflux pump function mechanism such as the one used by AcrB.
