The E3 ubiquitin ligase XIAP restricts Anaplasma phagocytophilum colonization of Ixodes scapularis ticks

J Infect Dis. 2013 Dec 1;208(11):1830-40. doi: 10.1093/infdis/jit380. Epub 2013 Jul 29.


Ubiquitination is a posttranslational modification that regulates protein degradation and signaling in eukaryotes. Although it is acknowledged that pathogens exploit ubiquitination to infect mammalian cells, it remains unknown how microbes interact with the ubiquitination machinery in medically relevant arthropods. Here, we show that the ubiquitination machinery is present in the tick Ixodes scapularis and demonstrate that the E3 ubiquitin ligase named x-linked inhibitor of apoptosis protein (XIAP) restricts bacterial colonization of this arthropod vector. We provide evidence that xiap silencing significantly increases tick colonization by the bacterium Anaplasma phagocytophilum, the causative agent of human granulocytic anaplasmosis. We also demonstrate that (i) XIAP polyubiquitination is dependent on the really interesting new gene (RING) catalytic domain, (ii) XIAP polyubiquitination occurs via lysine (K)-63 but not K-48 residues, and (iii) XIAP-dependent K-63 polyubiquitination requires zinc for catalysis. Taken together, our data define a role for ubiquitination during bacterial colonization of disease vectors.

Keywords: Ehrlichia; Rickettsia; insecta; ticks; ubiquitin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anaplasma phagocytophilum / physiology*
  • Animals
  • Arachnid Vectors / enzymology*
  • Arachnid Vectors / microbiology
  • Catalytic Domain
  • Ehrlichiosis / microbiology*
  • Humans
  • Ixodes / enzymology*
  • Ixodes / microbiology
  • RNA Interference
  • Signal Transduction
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination
  • X-Linked Inhibitor of Apoptosis Protein / genetics
  • X-Linked Inhibitor of Apoptosis Protein / metabolism*


  • X-Linked Inhibitor of Apoptosis Protein
  • Ubiquitin-Protein Ligases