A Farnesylated Coxiella burnetii Effector Forms a Multimeric Complex at the Mitochondrial Outer Membrane during

Laura F Fielden1, Jennifer H Moffatt2, Yilin Kang1

  • 1Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC, Australia.

Insights

Coxiella burnetii, the cause of Q fever, targets host cell mitochondria. A novel effector, MceA, localizes to the mitochondrial outer membrane and forms complexes, revealing mitochondria as a key infection target.

Area of Science:

  • Microbiology
  • Cell Biology
  • Infectious Diseases

Background:

  • Coxiella burnetii causes Q fever, establishing an intracellular niche within host cells.
  • Dot/Icm-type IVB secretion system is crucial for Coxiella survival and vacuole development.
  • Effector proteins translocated by the secretion system manipulate host cell processes.

Purpose of the Study:

  • Investigate the role of the conserved Coxiella effector CBU0077.
  • Determine the localization and function of CBU0077 during intracellular infection.
  • Identify novel host cell targets of Coxiella effectors.

Main Methods:

  • Localization studies of native and epitope-tagged CBU0077/MceA.
  • Analysis of MceA truncations for mitochondrial targeting.
  • Biochemical characterization of MceA in infected host cells.
  • Immunoprecipitation assays to determine MceA complex formation.

Main Results:

  • CBU0077 (renamed MceA) localizes to host cell mitochondria, not the Coxiella-containing vacuole.
  • Mitochondrial targeting is encoded within the first 84 amino acids of MceA.
  • MceA integrates into the mitochondrial outer membrane and forms homo-oligomeric complexes.
  • Host cell farnesylation does not affect MceA's mitochondrial localization.

Conclusions:

  • Mitochondria are a direct target for Coxiella effectors.
  • MceA is a novel effector protein that forms homo-oligomeric complexes on the mitochondrial outer membrane.
  • This finding expands our understanding of Coxiella's intracellular pathogenesis.

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