Richard P. Novick

Biosketch / Results /

Richard Novick

Recanati Family Professor of Science, Department of Microbiology;Professor, Department of Medicine
Skirball Institute

Contact Info

Address
540-562 First Avenue
New York, NY 10016

212/263-6290
Richard.Novick@med.nyu.edu

Education

1962-1963 — Department of Medicine, Vanderbilt University Hospital, Residency
— Dr. Novick was a Postdoctoral Fellow at the National Institute for Medical Research in London, England, 1961-1962. He was a Special Postdoctoral Fellow at The Rockefeller University, New York, NY from 1963-1965, PostDoctoral Training

Research Summary

Staphylococcus aureus, a major nosocomial pathogen, causes a wide variety of infections, from simple abscesses to fatal sepsis, plus toxinoses, such as food poisoning and toxic shock syndrome. S. aureus produces and secretes thirty or more specific pathogenicity factors, including superantigen toxins, hemolytic cytotoxins, tissue-component-degrading enzymes, and surface proteins, that interfere with host defenses. Its pathogenic versatility is compounded by its ability to develop resistance to new antibiotics almost as fast as they are introduced.

We have identified, sequenced, and characterized a global regulator, agr, that is the major regulatory element in a precisely orchestrated temporal program of virulence gene expression in vitro in Staphylococcus aureus. Agr consists of a 2-component signal transduction pathway, an autoinducing octapeptide (AIP) that serves as its ligand, and a regulatory RNA that controls target gene expression. The AIP contains a cyclic thioester bond between a conserved cysteine and the C-terminal carboxyl, which is presumably important for receptor binding. There are 4 or more groups of S. aureus strains that synthesize different AIPs; these activate agr expression within their group but inhibit agr expression in the other groups. We find that one of the AIPs can block infection by a heterologous strain in a mouse subcutaneous abscess model. We now study the biochemistry of AIP processing, the structure and function of the regulatory RNA, the expression of virulence factors in vivo, and the use of inhibitory peptides for antibacterial therapy.

Genes for staphylococcal superantigen toxins are often borne by plasmids and prophages. We find that the genes for TSST-1 and enterotoxin B are borne by a family of mobile pathogenicity islands, the first identified in staphylococci and the first for which mobility has been shown. These elements are 15 kb or more in size and are excised, caused to replicate, and encapsidated with high efficiency by certain staphylococcal phages. This results in an extremely high frequency of transduction. We are now analyzing the functions of these elements, the extent of their dissemination and the spectrum of pathogenicity genes that they carry.

Research Interests

Molecular Basis of Virulence in Staphylococcus aureus

Intra- and inter-generic transfer of pathogenicity island-encoded virulence genes by cos phages
Chen, John; Carpena, Nuria; Quiles-Puchalt, Nuria; Ram, Geeta; Novick, Richard P; Penades, Jose R
2015-04-27; 1751-7370,ISME journal - id: 1543842, year: 2015 Journal Article

Pathogenicity island-directed transfer of unlinked chromosomal virulence genes
Chen, John; Ram, Geeta; Penades, Jose R; Brown, Stuart; Novick, Richard P
2015-02-04; 1097-2765,Molecular cell - id: 1449882, year: 2015 Journal Article

An rpsL-based allelic exchange vector for Staphylococcus aureus
Chen, John; Ram, Geeta; Yoong, Pauline; Penades, Jose R; Shopsin, Bo; Novick, Richard P
2015-03-09; 0147-619x,Plasmid - id: 1481482, year: 2015 JOURNAL ARTICLE

Bacteriophage-mediated spread of bacterial virulence genes
Penadé JR; Chen, J; Quiles-Puchalt, N; Carpena, N; Novick, RP
2015-04-10; 1369-5274,Current opinion in microbiology - id: 1522632, year: 2015

Single-copy vectors for integration at the SaPI1 attachment site for Staphylococcus aureus
Chen, John; Yoong, Pauline; Ram, Geeta; Torres, Victor J; Novick, Richard P
2015-02-07; 0147-619x,Plasmid - id: 1456002, year: 2014 JOURNAL ARTICLE