The Coxiella burnetii effector protein CaeB modulates endoplasmatic reticulum (ER) stress signalling and is required for efficient replication in Galleria mellonella

Cell Microbiol. 2021 Apr;23(4):e13305. doi: 10.1111/cmi.13305. Epub 2021 Jan 28.


The obligate intracellular pathogen Coxiella burnetii is the causative agent of the zoonosis Q fever. C. burnetii infection can have severe outcomes due to the development of chronic infection. To establish and maintain an infection, C. burnetii depends on a functional type IVB secretion system (T4BSS) and, thus, on the translocation of effector proteins into the host cell. Here, we showed that the C. burnetii T4BSS effector protein CaeB targets the conserved endoplasmatic reticulum (ER) stress sensor IRE1 during ER stress in mammalian and plant cells. CaeB-induced upregulation of IRE1 RNase activity was essential for CaeB-mediated inhibition of ER stress-induced cell death. Our data reveal a novel role for CaeB in ER stress signalling modulation and demonstrate that CaeB is involved in pathogenicity in vivo. Furthermore, we provide evidence that C. burnetii infection leads to modulation of the ER stress sensors IRE1 and PERK, but not ATF6 during ER stress. While the upregulation of the RNase activity of IRE1 during ER stress depends on CaeB, modulation of PERK is CaeB independent, suggesting that C. burnetii encodes several factors influencing ER stress during infection.

Keywords: Coxiella burnetii; ER stress; Nicotiana benthamiana; apoptosis; effector proteins; type IV secretion system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism*
  • Cell Death
  • Coxiella burnetii / chemistry
  • Coxiella burnetii / genetics
  • Coxiella burnetii / pathogenicity*
  • DNA Replication
  • Endoplasmic Reticulum Stress*
  • HEK293 Cells
  • Host-Pathogen Interactions*
  • Humans
  • Larva / microbiology
  • Moths / microbiology*
  • Signal Transduction*


  • Bacterial Proteins