An RND-type efflux system in Borrelia burgdorferi is involved in virulence and resistance to antimicrobial compounds

Bunikis, Ignas,1981-Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Bergström (författare)

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.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
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

Denker, Katrin (författare)
Östberg, YngveUmeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten)(Swepub:umu)ynos0001 (författare)
Andersen, Christian (författare)
Benz, Roland (författare)
Bergström, SvenUmeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Bergström(Swepub:umu)svbe0001 (författare)
Umeå universitetInstitutionen för molekylärbiologi (Medicinska fakulteten) (creator_code:org_t)

Av författaren/redakt...: Bunikis, Ignas, ...; Denker, Katrin; Östberg, Yngve; Andersen, Christ ...; Benz, Roland; Bergström, Sven

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Cell och molekyl ...

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