Richard P. Novick

Professor, Skirball Institute of Biomolecular Medicine, Molecular Pathogenesis. Departments of Microbiology and Medicine

M.D., 1959 NYU School of Medicine

Lab Website: 

Keywords: Quorum Sensing; Autoinduction; Regulation; Mobile Genetic Elements; Transduction

 

Contact Information: 

Skirball Institute of Biomolecular Medicine
540 First Avenue 2nd floor, Lab 1-2
New York, N.Y. 10016
Office Tel: (212) 263-6290
Lab Tel: (212) 263-6294
Fax: (212) 263-5711
E-mail: richard.novick@med.nyu.edu

Administrative Contact:

Richard Stout
Tel: (212)263-6282
Email: richard.stout@med.nyu.edu


Regulation of virulence and molecular genetics of mobile pathogenicity islands in Staphylococcus aureus

In one of our projects, in collaboration with David Stokes and Tom Muir, we are attempting to determine the crystal structure of the staphylococcal agr signal receptor, AgrC, in order to define the mechanism of signal transduction by this protein. We are also working on the dynamics of agr activation in vitro at the single cell level, using fluorescent gene stags, and propose to move to an in vivo model as soon as the in vitro results are definitive.

In a second project, we are studying the mechanism by which the phage-inducible mobile pathogenicity islands of S. aureus interfere with the propagation of their helper bacteriophages. These mechanisms include an island-encoded protein that inhibits the phage-encoded small terminase subunit and also diversion of phage virion proteins to the formation of island-specific capsids. The interference also results in increased survival of phage- infected cells by an unknown mechanism. A recent finding is that the mobile islands can participate in genetic transduction, a process formerly thought to be the exclusive province of bacteriophages.

A third area of concentration in our lab is the development of methods to control, treat, or prevent staphylococcal infections. These methods include analysis of agr-encoded quorum-sensing peptides as inhibitors of virulence and for their potential to modify biofilm structure. They also include the development of an antistaphylococcal vaccine and of a powerful staphylolytic enzyme. Finally, we are exploring the potential of probiotics to prevent Clostridium difficile infections owing to antibiotic depletion of the normal intestinal flora.

Selected Publications:

Geeta Ram, John Chen, Krishan Kumar, Hope F. Ross, Carles Úbeda, Priyadarshan K. Damle, Kristin D. Lane, José R. Penadés, Gail E. Christie, and Richard P. Novick (2012). Staphylococcal pathogenicity island interference with helper phage reproduction is a paradigm of molecular parasitism. Proc Nat Acad Sci, US. Oct 2;109(40):16300-5. PMID: 22991467

Tormo-Más MA, Mir I, Shrestha A, Tallent SM, Campoy S, Lasa I, Barbé J, Novick RP, Christie GE, Penadés JR. (2010). Moonlighting bacteriophage proteins derepress staphylococcal pathogenicity islands. Nature 465:779-82. PMID: 20473284

Geisinger E, Muir TW, Novick RP. agr receptor mutants reveal distinct modes of inhibition by staphylococcal autoinducing peptides. Proc Natl Acad Sci U S A. 2009;106(4):1216-21. PMID: 19147840

George Cisar, E. A., E. Geisinger, et al. (2009). "Symmetric signalling within asymmetric dimers of the Staphylococcus aureus receptor histidine kinase AgrC." Mol Microbiol 74(1): 44-57. PMID: 19708918

Chen J, Novick RP. Phage-mediated intergeneric transfer of toxin genes. Science. 2009 Jan 2;323(5910):139-41. PMID: 19119236

Click here to see all publications in PubMed