| dc.description.abstract | Phage mediated lysis of bacteria is one of the most common events in the biosphere, and a greater understanding of phage lysis mechanisms may lead to the development of novel antibacterial therapies. As they encode a single, nonezymatic protein (“protein antibiotic) to effect lysis, small lytic phages offer great promise. The lysis proteins E and A2 of prototypical small phages phiX174 (Microviridae) and Qβ (Alloleviviridae) inhibit cell wall biosynthesis and cause lysis at the septum of a dividing cell. The lysis protein L of prototypical small phage MS2 (Leviviridae), conversely, causes lysis at random regions of the cell through an unknown mechanism. Although MS2 and phage M belong to the Leviviridae family, their lysis genes L and M lys have evolved at different locations (figure 1A) and cause different lysis phenotypes (figure 1B).
In this project, we investigated the lysis mechanism of M Lys. Based on similarities in membrane topology and lysis phenotype, we hypothesized that M Lys, like E, inhibits cell wall biosynthesis. Isolation of host mutants resistant to lysis yielded mutations in murJ, a proposed E. coli lipid II flippase involved in transporting cell wall precursors from the cell interior to the exterior. This suggests that M Lys confers lysis by inhibiting MurJ and thus host cell wall biosynthesis. This also provides additional support for the identification of MurJ as the E. coli lipid II flippase. | en |
