Download Expression and purification of AAA+ ClpB chaperone a potential

Biological function of the molecular chaperone ClpB from the bacterium Leptospira interrogans,
the causative agent of leptospirosis
Joanna Krajewska1, Zbigniew Arent2, Sabina Kędzierska-Mieszkowska1
1
Department of Biochemistry, Faculty of Biology, University of Gdańsk, Gdańsk, Poland
2
OIE Leptospirosis Reference Laboratory, Veterinary Sciences Division, Agri-Food and Biosciences Institute,
Belfast, UK
Abstract
Bacterial ClpB is a member of the Hsp100/Clp subfamily of the AAA+ ATPases that
solubilizes and reactivates stress-aggregated proteins in cooperation with the DnaK chaperone system.
The mechanism of protein disaggregation mediated by ClpB is linked to translocation of substrates
through the narrow central channel within the hexameric ring structure of ClpB. The data accumulated
over the last few years regarding several bacterial pathogens suggest that ClpB chaperone may play an
important role in their virulence. However, currently it is not clear what specific role ClpB plays
during bacterial infection. This chaperone can function either as a true virulence factor directly
involved in causing disease or as a virulence-associated protein that can be essential to enable the
pathogen to colonize its host. We are interested in this aspect of the function of ClpB.
We focused on ClpB from bacterium Leptospira interrogans (ClpBLi), a spirochete capable of
causing a disease known as leptospirosis. In humans the disease varies from an asymptomatic flu-like
illness to an acute life-threatening infection. Sources of this pathogen are mostly wild (rodents) or
domestic animals. Human are infected directly through exposure to urine or water contaminated with
urine of mammalian reservoir hosts. More than 1 million cases of severe leptospirosis are reported
each year, with a mortality rate of 5% to 20%. Leptospirosis is also a serious economic problem,
because it causes abortions, stillbirths, infertility, failure to thrive, reduced milk production, and death
in domestic animals such as cows, pigs, sheep, goats, horses and dogs. Despite its severity and global
importance, the molecular mechanisms of leptospiral pathogenesis remain still unknown.
The purpose of our study is to investigate a biochemical properties of ClpB and its function in
virulence of pathogenic bacteria.