e-journal
Specific targeting and killing of Gram-negative pathogens with an engineered phage lytic enzyme
Mode of action of pesticin and an engineered hybrid protein: (1) The Pesticin molecule consists of a N-terminal “FyuA binding” and a C-terminal lysozyme-like domain. After traversing the outer membrane pesticin degrades the peptidoglycan structural layer present in the periplasm resulting in cell killing. This translocation depends on an outer membrane protein and virulence factor—FyuA—but the mechanism by which this happens is not yet understood. (2) The
lysozyme-like domain of pesticin was substituted for T4 lysozyme to create a hybrid protein. The translocation of a hybrid also results in killing but unlike with pesticin this process is not inhibited by a periplasmic Pim protein. (3) Without additional means of disrupting the OM the externally added T4 lysozyme cannot effect killing. Abbreviations used in the figure: OM, outer membrane;Peri., periplasm; IM, inner membrane; PG, peptidoglycan.
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