An RND-type efflux system in Borrelia burgdorferi is involved in virulence and resistance to antimicrobial compounds.
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 homologs BesAB. We believe that our findings will be helpful in unraveling the pathogenic mechanisms of borreliae as well as in developing novel therapeutic agents aiming to block the function of this secretion apparatus.
Bunikis
Ignas
I
Department of Molecular Biology, Umeå University, Umeå, Sweden.
Denker
Katrin
K
Ostberg
Yngve
Y
Andersen
Christian
C
Benz
Roland
R
Bergström
Sven
S
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D025065:Borrelia burgdorferi / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D004269:DNA, Bacterial; D004352:Drug Resistance, Microbial / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D020868:Gene Silencing; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008969:Molecular Sequence Data; D030781:Organisms, Genetically Modified; D012333:RNA, Messenger / Q000378:metabolism; D014774:Virulence
D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D007473:Ion Channels; D026901:Membrane Transport Proteins; D012333:RNA, Messenger