Bacterial drug efflux pump (assembly model)

Bacterial drug efflux pump (assembly model)

Resistance to drugs remains a major obstacle in the treatment of infections caused by pathogenic bacteria. One drug resistance mechanism originates from the activity of transmembrane transporters that displace a broad range of antibiotics and other toxic compounds from the bacterium. In the case of Gram-negative bacteria, the toxic compound may need to be displaced across both an inner-membrane and an outer-membrane and the interstitial periplasm to be properly expelled from the cell. A special class of three-component efflux pumps accomplishes this task. Typically, the pumps are composed of an inner membrane protein, an outer membrane protein, and a protein that traverses the periplasm to links the two membrane proteins. A well studied representative of this family of efflux pumps is the Escherichia coli AcrB/AcrA/TolC assembly. Crystal structures are available for each of the three components of that tripartite assembly, but the structure of the ternary assembly is presently unknown. Accumulated structural and functional data suggest how the multi-drug efflux pump is assembled, and figure summarises these in a speculative model for the entire assembly based on docking the crystal structures of the individual components.