CmeB: a Bacterial Efflux Pump

Campylobacter jejuni causes over 400 million cases of enterocolitis worldwide, and is capable of triggering a severe autoimmune response known as Guillan-Barre syndrome. Previous methods of treatment for C. jejuni infection relied upon fluoroquinolone and macrolide antibiotics; however, C. jejuni has become resistant to these medications.

C. jejuni resistance to antibiotics is mediated by a variety of mechanisms, which include multidrug efflux via complex pump systems. The best-characterized multidrug efflux in C. jejuni is the CmeABC tripartite system. The genes for each component of the complex are tandemly linked at the cmeABC locus. This multidrug efflux system consists of:

1. CmeB : an inner-membrane, homotrimeric, proton-powered efflux pump
   
2. CmeA: a hexameric periplasmic adaptor protein, connecting CmeB to CmeC
3. CmeC: an outer-membrane channel protein

In this tutorial, we will examine the overall structure and conformational changes CmeB multidrug efflux pump. In their 2017 study, Chih-Chia et al. crystallized the CmeB trimer in a variety of conformations, and used single-molecule Fluorescence Energy Transfer (sm-FRET) to observe the protein's drug transport cycle (PubMed). The resultant CmeB structures will provide valuable insight into the pump's key structural features, cycle of conformational changes, and drug transport capabilities. Eventually, this information may facilitate the discovery of new treatments for C. jejuni infection, which would target and somehow inactivate CmeB.