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POSTERS - BLAST X - University of Utah

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<strong>BLAST</strong> X Poster #47<br />

THE ESSENTIAL NATURE OF THE WALK/WALR SIGNAL TRANSDUCTION PATHWAY IS<br />

LINKED TO CELL WALL HYDROLASE ACTIVITY IN STAPHYLOCOCCUS AUREUS<br />

Aurélia Delauné 1 , Olivier Poupel 1 , Adeline Mallet 2 , Sarah Dubrac 1 , and Tarek Msadek 1<br />

Biology <strong>of</strong> Gram-positive Pathogens 1 , Department <strong>of</strong> Microbiology, Plateforme de Microscopie<br />

Ultrastructurale 2 , Imagopole, Institut Pasteur, 25 rue du Dr. Roux, 75015 Paris, France<br />

Staphylococcus aureus, a major Gram-positive human pathogen, is a leading cause <strong>of</strong><br />

both nosocomial and community infections due to its considerable capacity for adaptation. One<br />

<strong>of</strong> the principal mechanisms involved in this process are the so-called two-component systems,<br />

bacterial signal transduction pathways with a sensor histidine kinase that is autophosphorylated<br />

in response to specific environmental stimuli and then transfers the phosphoryl group to its<br />

cognate response regulator, which consequently regulates target gene expression. The WalKR<br />

two-component system is well conserved and specific to low G+C Gram-positive bacteria,<br />

including Bacillus subtilis, Staphylococcus aureus and Streptococcus pneumoniae. This system<br />

has been shown to be essential for cell viability.<br />

We have recently demonstrated that the WalKR system positively controls autolytic<br />

activity, and identified ten genes belonging to the WalKR regulon that appear to be involved in<br />

S. aureus cell wall degradation. Reasoning that the essential nature <strong>of</strong> this signaling pathway<br />

may be related to its role as a master regulatory system for cell wall metabolism, we tested<br />

whether uncoupling autolysin gene expression from WalKR-dependent regulation could<br />

compensate for the essential nature <strong>of</strong> the system. Several genes from the WalKR regulon were<br />

expressed from a cadmium chloride-inducible promoter in a WalKR-independent manner.<br />

Candidate genes were identified whose expression allowed cells to grow in the absence <strong>of</strong><br />

WalKR.<br />

98

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