an rnd-type efflux system in borrelia burgdorferi is involved in virulence and resistance to antimicrobial compounds一个rnd-type流出系统参与毒性和伯氏疏螺旋体抗抗菌化合物.pdfVIP

An RND-Type Efflux System in Borrelia burgdorferi Is Involved in Virulence and Resistance to Antimicrobial Compounds 1,2 3 ¨ 1,2¤ 3 3 Ignas Bunikis , Katrin Denker , Yngve Ostberg , Christian Andersen , Roland Benz , Sven ¨ 1,2* Bergstrom ˚ ˚ ˚ ˚ 1 Department of Molecular Biology, Umea University, Umea, Sweden, 2 Laboratory for Molecular Infection Medicine Sweden (MIMS), Umea University, Umea, Sweden, ¨ ¨ ¨ ¨ 3 Lehrstuhl fur Biotechnologie, Biozentrum der Universitat Wurzburg, Wurzburg, Germany Abstract Borrelia burgdorferi is remarkable for its ability to thrive in widely different environments due to its ability to infect various organisms. In comparison to enteric Gram-negative bacteria, these spirochetes have only a few transmembrane proteins some of which are thought to play a role in solute and nutrient uptake and excretion of toxic substances. Here, we have identified an outer membrane protein, BesC, which is part of a putative export system comprising the components BesA, BesB and BesC. We show that BesC, a TolC homolog, forms channels in planar lipid bilayers and is involved in antibiotic resistance. A besC knockout was unable to establish infection in mice, signifying the importance of this outer membrane channel in the mammalian host. The biophysical properties of BesC could be explained by a model based on the channel- tunnel structure. We have also generated a structural model of the efflux apparatus showing the putative spatial orientation of BesC with respect to the AcrAB homo