Molecular mimicry by an F-box effector of Legionella pneumophila hijacks a conserved polyubiquitination machinery within macrophages and protozoa

Christopher T. Price, Souhaila M. Al Khodor, Tasneem Al-Quadan, Marina Santic, Fabien Habyarimana, Awdhesh Kalia, Yousef Abu Kwaik

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

The ability of Legionella pneumophila to proliferate within various protozoa in the aquatic environment and in macrophages indicates a remarkable evolution and microbial exploitation of evolutionarily conserved eukaryotic processes. Ankyrin B (AnkB) of L. pneumophila is a non-canonical F-box-containing protein, and is the only known Dot/Icm-translocated effector of L. pneumophila essential for intra-vacuolar proliferation within both macrophages and protozoan hosts. We show that the F-box domain of AnkB and the 9L10P conserved residues are essential for intracellular bacterial proliferation and for rapid acquisition of polyubiquitinated proteins by the Legionella-containing vacuole (LCV) within macrophages, Dictyostelium discoideum, and Acanthamoeba. Interestingly, translocation of AnkB and recruitment of polyubiquitinated proteins in macrophages and Acanthamoeba is rapidly triggered by extracellular bacteria within 5 min of bacterial attachment. Ectopically expressed AnkB within mammalian cells is localized to the periphery of the cell where it co-localizes with host SKP1 and recruits polyubiquitinated proteins, which results in restoration of intracellular growth to the ankB mutant similar to the parental strain. While an ectopically expressed AnkB-9L10P/AA variant is localized to the cell periphery, it does not recruit polyubiquitinated proteins and fails to trans-rescue the ankB mutant intracellular growth defect. Direct in vivo interaction of AnkB but not the AnkB-9L10P/AA variant with the host SKP1 is demonstrated. Importantly, RNAi-mediated silencing of expression of SKP1 renders the cells non-permissive for intracellular proliferation of L. pneumophila. The role of AnkB in exploitation of the polyubiquitination machinery is essential for intrapulmonary bacterial proliferation in the mouse model of Legionnaires' disease. Therefore, AnkB exhibits a novel molecular and functional mimicry of eukaryotic F-box proteins that exploits conserved polyubiquitination machinery for intracellular proliferation within evolutionarily distant hosts. Copyright:

Original languageEnglish
Article numbere1000704
JournalPLoS Pathogens
Volume5
Issue number12
DOIs
Publication statusPublished - Dec 2009
Externally publishedYes

Fingerprint

Ankyrins
Molecular Mimicry
Legionella pneumophila
Macrophages
F-Box Proteins
Acanthamoeba
Proteins
Legionnaires' Disease
Legionella
Dictyostelium
Growth
RNA Interference
Vacuoles
Bacteria

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Molecular mimicry by an F-box effector of Legionella pneumophila hijacks a conserved polyubiquitination machinery within macrophages and protozoa. / Price, Christopher T.; Al Khodor, Souhaila M.; Al-Quadan, Tasneem; Santic, Marina; Habyarimana, Fabien; Kalia, Awdhesh; Kwaik, Yousef Abu.

In: PLoS Pathogens, Vol. 5, No. 12, e1000704, 12.2009.

Research output: Contribution to journalArticle

Price, Christopher T. ; Al Khodor, Souhaila M. ; Al-Quadan, Tasneem ; Santic, Marina ; Habyarimana, Fabien ; Kalia, Awdhesh ; Kwaik, Yousef Abu. / Molecular mimicry by an F-box effector of Legionella pneumophila hijacks a conserved polyubiquitination machinery within macrophages and protozoa. In: PLoS Pathogens. 2009 ; Vol. 5, No. 12.
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