Molecular genetic and structural studies of toxic shock syndrome toxin-1 (TSST-1) will be continued. Dr. Novick has shown that the determinant of TSST-1 (tstH) is carried by a site-specific transposon, Tn557, and analysis of the molecular genetics of Tn557 is proposed. He has found that the pathogenic activities of TSST-1 are localized to the N-terminal half of the molecule, the T cell mitogenicity to the C-terminal half. The precise nature of these determinants will be analyzed and contributory epitopes defined. TSST-1 is lethal for endothelial cells but stimulatory for T cells, suggesting that different types of receptors may be involved. TSST-1 receptors will be isolated from endothelial and T cells and compared. TSST-1 synthesis is growth phase-regulated and a mutational analysis of this regulation is proposed. Finally, the investigator has shown that the streptococcal toxic shock-like toxin, SpeA, is regulated similarly to TSST-1 and a mutational study of toxin regulation in Streptococcus pyogenes is planned.
| Ram, Geeta; Ross, Hope F; Novick, Richard P et al. (2018) Conversion of staphylococcal pathogenicity islands to CRISPR-carrying antibacterial agents that cure infections in mice. Nat Biotechnol 36:971-976 |
| Martínez-Rubio, Roser; Quiles-Puchalt, Nuria; Martí, Miguel et al. (2017) Phage-inducible islands in the Gram-positive cocci. ISME J 11:1029-1042 |
| Novick, Richard P; Ram, Geeta (2017) Staphylococcal pathogenicity islands-movers and shakers in the genomic firmament. Curr Opin Microbiol 38:197-204 |
| Novick, Richard P; Ram, Geeta (2016) The Floating (Pathogenicity) Island: A Genomic Dessert. Trends Genet 32:114-126 |
| Penadés, José R; Chen, John; Quiles-Puchalt, Nuria et al. (2015) Bacteriophage-mediated spread of bacterial virulence genes. Curr Opin Microbiol 23:171-8 |
| Chen, John; Carpena, Nuria; Quiles-Puchalt, Nuria et al. (2015) Intra- and inter-generic transfer of pathogenicity island-encoded virulence genes by cos phages. ISME J 9:1260-3 |
| Chen, John; Ram, Geeta; Penadés, José R et al. (2015) Pathogenicity island-directed transfer of unlinked chromosomal virulence genes. Mol Cell 57:138-49 |
| Chen, John; Ram, Geeta; Yoong, Pauline et al. (2015) An rpsL-based allelic exchange vector for Staphylococcus aureus. Plasmid 79:8-14 |
| Ram, Geeta; Chen, John; Ross, Hope F et al. (2014) Precisely modulated pathogenicity island interference with late phage gene transcription. Proc Natl Acad Sci U S A 111:14536-41 |
| Chen, John; Yoong, Pauline; Ram, Geeta et al. (2014) Single-copy vectors for integration at the SaPI1 attachment site for Staphylococcus aureus. Plasmid 76:1-7 |
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