Protein Antibiotic of Phage M
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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.
Min, Lorna (2017). Protein Antibiotic of Phage M. Undergraduate Research Scholars Program. Available electronically from