POSTERS - BLAST X - University of Utah

BLAST X Mon. Morning Session
THE WalK/WalR ESSENTIAL SIGNAL TRANSDUCTION PATHWAY AND CELL WALL
HOMEOSTASIS IN STAPHYLOCOCCUS AUREUS
Sarah Dubrac 1 , Aurélia Delauné 1 , Olivier Poupel 1 , Adeline Mallet 2 , Tarek Msadek 1
Biology of Gram-positive Pathogens 1 , Department of Microbiology, Plateforme de Microscopie
Ultrastructurale 2 , Imagopole, Institut Pasteur, 25 rue du Dr. Roux, 75015 Paris, France
The highly conserved WalK/WalR (aka YycG/YycF) two-component system is specific to
low G+C % Gram-positive bacteria. While this system is essential for cell viability, both the
nature of its regulon and its physiological role remained mostly uncharacterized. We have
recently shown that the S. aureus WalKR system positively controls autolytic activity, in
particular that of the major autolysins, AtlA, LytM and Sle1, and identified at least ten genes
belonging to the WalKR regulon that are known or thought to be involved in S. aureus cell wall
degradation. While none of these genes appears to be essential, we have shown that their
global regulation by the WalKR system results in a drastic down regulation of cell wall dynamics,
with a complete arrest of both cell wall biosynthesis and turn over under WalKR depletion. As a
consequence of these molecular disorders TEM observations revealed that the cell wall of
WalKR depleted cells was significantly thicker and division septa were abnormally distributed.
Recent advances presented here have shown that this global regulation is directly linked to
WalKR essentiality. While the walRK genes are essential, the WalKR system is inducible since
it is assumed that the WalR response regulator is only active when phosphorylated. While the
activation signal is still unknown, several recent results suggest that it could be related to cell
wall homeostasis.
As cell wall metabolism is a major parameter influencing virulence and particularly the
innate immune response, we are now interested in characterizing the impact of WalKR on
S. aureus virulence. Beyond the regulation of genes involved in cell wall metabolism, we have
also shown that the WalKR system activates expression of at least two genes involved in
interactions with the extracellular host matrix and influences the capacity of S. aureus to adhere
to the host matrix.
References:
1. Dubrac, S., I. G. Boneca, O. Poupel, and T. Msadek. 2007. New insights into the
WalK/WalR (YycG/YycF) essential signal transduction pathway reveal a major role in
controlling cell wall metabolism and biofilm formation in Staphylococcus aureus. J.
Bacteriol. 189:8257-69.
2. Dubrac, S., and T. Msadek. 2008. Tearing down the wall: peptidoglycan metabolism
and the WalK/WalR (YycG/YycF) essential two-component system. Adv. Exp. Med. Biol.
631:214-28.
3. Dubrac, S., P. Bisicchia, K. M. Devine and T. Msadek. 2008. A matter of life and
death: cell wall homeostasis and the WalKR (YycGF) essential signal transduction
pathway. Mol. Microbiol. 70: (in press)
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