Dr. Charles Stewart
Bacteriophage SPO1
When Bacillus subtilis is infected by bacteriophage SPO1, the phage directs the remodeling of the host cell, converting it from a factory for its own reproduction into a factory for reproduction of phage. The host's biosynthetic machinery is subverted to the purposes of the phage. Most or all synthesis of host DNA, RNA, and protein is shut off, presumably to prevent those syntheses from competing with the corresponding phage biosyntheses for materials, energy, and access to biosynthetic machinery. Such global redirection of the cell's resources requires regulatory mechanisms of great sophistication and specificity, to eliminate the host-specific biosyntheses, while exactly the same processes, specific to the phage genome, proceed with great efficiency in the same cell. Our objective is to elucidate those regulatory mechanisms.
We have identified more than two dozen SPO1 genes whose products participate in this host-takeover process. We are studying the functions of those gene products, both by knocking out the function of specific genes by site-specific mutagenesis, and by expressing individual genes and gene combinations in uninfected cells. Specific gene products have been shown to: (1) inhibit host RNA synthesis; (2) inhibit host DNA synthesis; (3) inhibit host cell division; (4) regulate the activity of other host-takeover gene products; and (5) regulate the expression of host-takeover genes. Since many of the gene products inhibit essential host functions, and are therefore lethal to the bacterium when expressed in uninfected cells, they could potentially serve as the basis for development of new antibiotics.
Contact Information
|
