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The above is a diagrammatic representation of host-takeover. Top: Uninfected cell, replicating and transcribing its DNA. Middle: Newly infected cell, expressing the host-takeover genes of SPO1. Bottom: Later in infection, host genome has been shut down, while phage genome is actively replicated and expressed.

Infection of Bacillus subtilis by bacteriophage SPO1 causes profound changes in the genetic processes of the host cell. 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 enormous efficiency in the same cell.

We are analyzing the mechanisms by which SPO1 accomplishes this takeover of the host cell. We have identified a cluster of 24 genes in the terminal redundancy of SPO1, which specifies most or all of the necessary machinery. By observing the effect of expression of each gene in uninfected cells, and the effect of mutational inactivation of each gene on the progress of infection, we are defining the specific role of each of the 24 genes. The cellular targets of four of the genes have been tentatively identified as: RNA polymerase, cell division, protein synthesis, and a response-regulator protein.

The broad spectrum bactericidal activity of some of these genes makes them a potential source of new antibiotics.