title: The Coxiella burnetii type IV secretion system substrate CaeB inhibits intrinsic apoptosis at the mitochondrial level.
abstract: Manipulation of host cell apoptosis is a virulence property shared by many intracellular pathogens to ensure productive replication. For the obligate intracellular pathogen Coxiella burnetii anti-apoptotic activity, which depends on a functional type IV secretion system (T4SS), has been demonstrated. Accordingly, the C. burnetii T4SS effector protein AnkG was identified to inhibit pathogen-induced apoptosis, possibly by binding to the host cell mitochondrial protein p32 (gC1qR). However, it was unknown whether AnkG alone is sufficient for apoptosis inhibition or if additional effector proteins are required. Here, we identified two T4SS effector proteins CaeA and CaeB (C. burnetii anti-apoptotic effector) that inhibit the intrinsic apoptotic pathway. CaeB blocks apoptosis very efficiently, while the anti-apoptotic activity of CaeA is weaker. Our data suggest that CaeB inhibits apoptosis at the mitochondrial level, but does not bind to p32. Taken together, our results demonstrate that C. burnetii harbours several anti-apoptotic effector proteins and suggest that these effector proteins use different mechanism(s) to inhibit apoptosis.
authors.affiliation: Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Wasserturmstraße 3/5, D-91054, Erlangen, Germany.
authors.forename: Leonie
authors.initials: L
authors.lastname: Klingenbeck
authors.forename: Rita A
authors.initials: RA
authors.lastname: Eckart
authors.forename: Christian
authors.initials: C
authors.lastname: Berens
authors.forename: Anja
authors.initials: A
authors.lastname: Lührmann
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001426:Bacterial Proteins / Q000378:metabolism*; D058947:Bacterial Secretion Systems; D002460:Cell Line; D016997:Coxiella burnetii / Q000378:metabolism / Q000502:physiology*; D006224:Cricetinae; D004847:Epithelial Cells / Q000382:microbiology / Q000502:physiology*; D005347:Fibroblasts / Q000382:microbiology / Q000502:physiology*; D006801:Humans; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D037521:Virulence Factors