Poster Presentation The 45th Lorne Conference on Protein Structure and Function 2020

The Coxiella burnetii effector protein MceB targets the mitochondria during infection (#100)

Laura Fielden 1 , Nichollas E Scott 2 , Hayley J Newton 2 , Diana Stojanovski 1
  1. Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria, Australia
  2. Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia

Mitochondria are essential organelles, fundamental to eukaryotic cell function and survival. Perhaps best known for their role in energy production, mitochondria are also central to many cellular processes, including calcium homeostasis, lipid metabolism, heme biosynthesis and immune signalling. With such diverse cellular roles, it is no surprise that virulence factors of both bacterial and viral origin target the host cell mitochondria during infection.  

Coxiella burnetii is a unique intracellular bacterial pathogen and the causative agent of Q fever. The bacterium infects alveolar macrophages and replicates within a highly acidic, lysosome-like vacuole, termed the Coxiella-containing vacuole (CCV). During infection, C. burnetii translocates over 130 bacterial effector proteins into the host cytosol via a Type 4 Secretion System (T4SS). Effector proteins translocated into the cell modulate cellular functions to facilitate CCV development and bacterial replication.

We previously identified mitochondria as a bona fide target of C. burnetii effector proteins during infection (1). To discover additional effector proteins targeted to this organelle we purified mitochondria from infected macrophages and performed mass spectrometry. This identified a cohort of 7 C. burnetii effectors enriched alongside the organelle during infection, representing novel, mitochondrial-targeted effector proteins. Of this subset, we further investigated MceB (Mitochondria Coxiella effector B). By confocal microscopy, MceB localised to the mitochondria and this targeting relies on information within the N-terminus of the protein. MceB is imported into the organelle and integrated into the inner mitochondria membrane (IMM). Analysis of the interactome of this effector protein revealed MceB interacts with several resident IM proteins involved in mitochondrial quality control and IMM architecture. Thus, during infection C. burnetii targets effector proteins to the mitochondria, modulating organelle function to create an environment conducive to bacterial replication.        

  1. L. F. Fielden et al., A Farnesylated Coxiella burnetii Effector Forms a Multimeric Complex at the Mitochondrial Outer Membrane during Infection. Infect Immun 85, (2017).