Drexel University College of Medicine

Bacillus anthracis and regulation of its virulence genes, cholesterol dependent cytolysin (CDC). While studying the regulation of expression of Bacillus anthracis cholesterol-dependent cytolysin, anthrolysin O (ALO), we discovered a 28 AA peptide.  We demonstrated that this peptide is involved in regulation of ALO expression and named it Anthrolysin O Regulating Peptide (Arp1).  The arp1 gene is located directly upstream of alo forming an operon.  We showed that Arp1 not only regulates ALO, but also hundreds of genes, as shown by microarray analyses comparing B. anthracis strains 7702 (the parent strain), and 7702 (pDUM105) (the parent strain over-expressing arp1 in trans).  Among the genes under the control of arp1 are at least 14 genes from the PlcR regulon, including putative virulence factors, which were previously believed to be silent in B. anthracis.  The expression of at least 33 genes involved in anaerobic metabolism is increased in the arp1 overproducing strain.  Furthermore, the arp1 knock out strain displays phenotypes that suggest a role in virulence; such as faster anaerobic growth, slower germination in 10% serum and delayed outgrowth from macrophages.  Regulated virulence gene expression and adaptation to niches having different oxygen tension are important for the survival of B. anthracis in its host and warrant further investigation.  We investigate the role that the Arp1 regulon plays in B. anthracis pathogenicity, in particular in its interactions with macrophages.

Selected Publications

1. Simon, D., Rouault, A., and M.-C. Chopin. Protoplast transformation of group N streptococci with cryptic plasmids. FEMS Microbiol. Lett., 26: 239-241, 1985.
2. Chopin, M.-C., Chopin, A., Rouault, A., and D. Simon. Cloning in Streptococcus lactis of plasmid-mediated ultra-violet resistance and incidence on prophage stability. Appl. Environ. Microbiol., 51: 233-237, 1986.
3. Simon, D., Rouault, A., and M.-C. Chopin. High-efficiency transformation of Streptococcus lactis protoplasts by plasmid DNA. Appl. Environ. Microbiol., 52: 394-395, 1986.
4. Simon, D., and A. Chopin. Construction of a vector plasmid family and its use for molecular cloning in Streptococcus lactis. Biochimie. 70: 559-566, 1988.
5. Simon, D., and J. J. Ferretti. High-efficiency electrotransformation of Streptococcus pyogenes. in: Streptococcal Genetics (Dunny G.M., Cleary P.P. and McKay L.L. eds). Amer. Soc. Microbiol., Washington, D.C, 1990.
6. Ferretti, J. J., Huang, T. T., Hynes, W. L., Horst, M., Simon, D., Suvorov, A., and C.-E. Yu. Extracellular products genes of Group A streptococci. in: Streptococcal Genetics (Dunny G.M., Cleary P.P. and McKay L.L. eds). Amer. Soc. Microbiol., Washington, D.C., 1990.
7. Simon, D., and J. J. Ferretti. Electrotransformation of Streptococcus pyogenes with plasmid and linear DNA. FEMS Microbiol. Lett., 82: 219-224, 1990.
8. Banas, J. A., Simon, D., Williams, L. K., Ferretti, J. J., and R. R. B. Russell. Analysis of a primer-independent GTF-I Streptococcus salivarius. FEMS Microbiol. Lett., 123: 349-354, 1994.
9. Holm, S. E., Ferretti, J. J., Simon, D., and K. H. Johnston. Deletion of a streptokinase gene eliminates the nephritogenic capacity of a type 49 strain. In Proceedings of the XI Lancefield International Symposium on Streptococci and Streptococcal Diseases. Gustav Fisher Verlag, Stuttgart, 1991.
10. Simon, D., and R. F. Rest. Escherichia coli expressing a Neisseria gonorrhoeae opacity associated (Opa) outer membrane protein invade human epithelial cells. Proc. Nat. Acad. Sci. USA. 89: 5512-5516, 1992.
11. Rest, R. F., Liu, J., Talukdar, R., Frangipane, J. V., and D. J. J. Simon. Interaction of Pathogenic Neisseria with Host Defenses: What happens in vivo? Annals N. Y. Acad. Sci., 730: 182-196, 1994.
12. Gorby, G., Simon, D., and R. F. Rest. Escherichia coli that express Neisseria gonorrhoeae opacity-associated proteins attach to and invade human fallopian tube epithelium. Annals N. Y. Acad. Sci., 730: 286-289, 1994.
13. Simon, D., Liu, J. T., Blake, M. S., Blake, C. R., and R. F. Rest. Structure-function studies with Neisseria gonorrhoeae Opa outer membrane proteins expressed in Escherichia coli. Annals N. Y. Acad. Sci., 797: 253-254, 1996.
14. Pozzi, G., Masala, L., Iannelli, F., Manganelli, R., Havarstein, L. S., Piccoli, L., Simon, D., and D. A. Morisson. Competence for genetic transformation in encapsulated strains of Streptococcus pneumoniae: Two allelic variants of the peptide pheromone. J. Bacteriol. 178: 6087-6090, 1996.
15. Polissi, A., Pontiggia, A., Feger, G., Altieri, M., Mottl, H., Ferrari, L., and D. Simon. Large scale identification of virulence genes in Streptococcus pneumoniae. Infect. Immun., 66(12): 5620-5629, 1999.