Enteric pathogens deploy cell cycle inhibiting factors to block the bactericidal activity of Perforin-2.

Perforin-2 (MPEG1) is an effector of the innate immune system that limits the proliferation and spread of medically relevant Gram-negative, -positive, and acid fast bacteria. We show here that a cullin-RING E3 ubiquitin ligase (CRL) complex containing cullin-1 and βTrCP monoubiquitylates Perforin-2 in response to pathogen associated molecular patterns such ...
as LPS. Ubiquitylation triggers a rapid redistribution of Perforin-2 and is essential for its bactericidal activity. Enteric pathogens such as Yersinia pseudotuberculosis and enteropathogenic Escherichia coli disarm host cells by injecting cell cycle inhibiting factors (Cifs) into mammalian cells to deamidate the ubiquitin-like protein NEDD8. Because CRL activity is dependent upon NEDD8, Cif blocks ubiquitin dependent trafficking of Perforin-2 and thus, its bactericidal activity. Collectively, these studies further underscore the biological significance of Perforin-2 and elucidate critical molecular events that culminate in Perforin-2-dependent killing of both intracellular and extracellular, cell-adherent bacteria.
Mesh Terms:
Animals, Cell Cycle, Cell Line, Cullin Proteins, Enteropathogenic Escherichia coli, Host-Pathogen Interactions, Humans, Microbial Viability, Pore Forming Cytotoxic Proteins, Ubiquitins, Virulence Factors, Yersinia pseudotuberculosis
Elife
Date: Sep. 29, 2015
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