The variation of RND efflux pumps in E. coli

Antibiotic resistance is a serious global threat, associated mortality is predicted to reach 10 million a year globally by 2050. Bacteria have many mechanisms for evading the effects of antimicrobials including efflux pumps.
Tripartite multidrug resistance efflux pump systems, such as that formed by the AcrA, AcrB, and TolC proteins are responsible for inherent resistance of Gram-negative bacteria to many antibiotics effective against Gram-positive bacteria. Genetic inactivation of efflux pump genes results in multi-drug hyper-susceptibility, and in the absence of an intact AcrAB-TolC system some chromosomal and transmissible antibiotic resistance genes no longer confer clinically relevant levels of resistance.
Our knowledge of structure, function and inhibition of efflux pumps are based upon the sequence of the coding genes in a small number of well characterised type strains (such as K12 MG1655) with the assumption that all efflux proteins have the same sequence and function in the same manner. The objective of this project is to explore RND pump variation within the E. coli population with the aim of determining if this assumption is justified and whether polymorphisms in the sequence affect the efficiency of substrate efflux.