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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

Amino Acid Sequence

Animals

Anti-Bacterial Agents/pharmacology

Bacterial Outer Membrane Proteins/genetics/*metabolism

Bacterial Proteins/genetics/*metabolism

Borrelia burgdorferi/genetics/metabolism/*pathogenicity

DNA; Bacterial

Drug Resistance; Microbial/*physiology

Gene Expression Regulation; Bacterial/genetics

Gene Silencing

Ion Channels/drug effects/metabolism

Membrane Transport Proteins/genetics/*metabolism

Mice

Mice; Inbred C3H

Microbial Sensitivity Tests

Models; Molecular

Molecular Sequence Data

Organisms; Genetically Modified

RNA; Messenger/metabolism

Virulence

Molecular biology

Molekylärbiologi

molekylärbiologi

Molecular Biology

Publikations- och innehållstyp

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