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

Ryan M. McCormack, Kirill Lyapichev, Melissa L. Olsson, Eckhard R. Podack, George Munson

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere06505
JournaleLife
Volume4
Issue numberSeptember2015
DOIs
StatePublished - Sep 29 2015

Fingerprint

Pathogens
Cell Cycle
Cells
Bacteria
Cullin Proteins
Ubiquitins
Yersinia pseudotuberculosis
Enteropathogenic Escherichia coli
Ubiquitin-Protein Ligases
Immune system
Ubiquitination
Ubiquitin
Escherichia coli
perforin 2
Immune System
Acids

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

Cite this

Enteric pathogens deploy cell cycle inhibiting factors to block the bactericidal activity of Perforin-2. / McCormack, Ryan M.; Lyapichev, Kirill; Olsson, Melissa L.; Podack, Eckhard R.; Munson, George.

In: eLife, Vol. 4, No. September2015, e06505, 29.09.2015.

Research output: Contribution to journalArticle

McCormack, Ryan M. ; Lyapichev, Kirill ; Olsson, Melissa L. ; Podack, Eckhard R. ; Munson, George. / Enteric pathogens deploy cell cycle inhibiting factors to block the bactericidal activity of Perforin-2. In: eLife. 2015 ; Vol. 4, No. September2015.
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