Campylobacter jejuni is responsible for more than 400 million cases of human enterocolitis each year worldwide. This infection is capable of triggering an autoimmune response and initiating the development of Guillain-Barre syndrome. C. jejuni is frequently found in the intestinal tracts of animals and can be spread to humans through contaminated food, water, or raw milk. Fluoroquinolone and macrolide antibiotics are commonly used as treatment strategies for human campylobacteriosis. However, Campylobacter has become resistant to these antimicrobials. Recently, the Centers for Disease Control and Prevention have listed drug-resistant Campylobacter as a serious threat in the United States. Resistance of Campylobacter to antibiotics is mediated by multiple mechanisms and multidrug efflux is one of the major causes of failure of drug-based treatments. Multidrug efflux pumps contribute significantly to both intrinsic and acquired resistance to various antimicrobials in C. jejuni. The resistance compromises the effectiveness of clinical therapy and affects the duration of clinical treatment.
The best characterized multidrug efflux system in C. jejuni is the Cme (Campylobacter multidrug efflux) tripartite system. The Cme locus consists of three tandemly linked genes (cmeABC) encoding protein components of the tripartite Cme efflux pump (CmeA, CmeB, and CmeC), where all three components are absolutely required for substrate expulsion. This tripartite system is composed of the CmeB efflux pump, an inner membrane resistance-nodulation-cell division (RND) transport protein that contains substrate-binding sites and transduces the electrochemical energy required for pumping drugs out of the cell; the CmeA periplasmic protein, a member of the membrane fusion protein family; and the CmeC outer membrane-associated protein that is integral to the outer membrane. Here you can see the crystal structure of the Campylobacter jejuni multidrug efflux pump CmeB (PDB code: 5LQ3)
Structure rendered with @proteinimaging, post-processed with @stylar and depicted with @corelphotopaint
#molecularart #scivis #campylobacter #resistance #multidrug #efflux #pump #xray
