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F. Antibiotic Activities of SPO1 Proteins.

Since many of the SPO1 host-takeover proteins target essential functions of the bacterial cell, many of them (including at least the products of genes 37, 38, 39, 41, 44, 45/46, 50/51, 52, and 56) are bactericidal or bacteriostatic when expressed individually in uninfected cells. Each of these toxic proteins represents a possible new antibiotic mechanism. Because of their large size, immunogenicity, and typically intracellular activity, it would be a challenge to deliver such proteins to their targets in therapeutic quantities. However, they can serve as leads, to the identification of new bacterial cell targets for antibiotics, and to the design of peptidomimetic small molecules having the same antibiotic activity as the full-length protein. Most of the proteins are as toxic to E. coli as to B. subtilis, suggesting that their targets are conserved across a broad spectrum of bacteria, and that both gram-positive and gram negative pathogens are likely to be targeted by these antibiotic mechanisms. The proteins target a variety of bacterial processes, and, since none of them shows substantial homology to any known protein, it is likely that many of the mechanisms revealed will be novel.

A. General Introduction to bacteriophage SPO1.

B. GP44, gp50, and gp51 regulate the shutoff of host biosyntheses indirectly, by regulating expression of the genes of the host-takeover module.

C. GP40 plays a direct role in shutoff of both host DNA and RNA synthesis, and gp38 and gp39 regulate both shutoffs, by direct participation in the shutoff processes.

D. GP56 (possibly assisted by gp57 and gp58) inhibits host cell division.

E. GP55-53 may inhibit host protein synthesis.

F. Antibiotic Activities of SPO1 Proteins.