title: Evolutionary conservation of infection-induced cell death inhibition among Chlamydiales.
abstract: Control of host cell death is of paramount importance for the survival and replication of obligate intracellular bacteria. Among these, human pathogenic Chlamydia induces the inhibition of apoptosis in a variety of different host cells by directly interfering with cell death signaling. However, the evolutionary conservation of cell death regulation has not been investigated in the order Chlamydiales, which also includes Chlamydia-like organisms with a broader host spectrum. Here, we investigated the apoptotic response of human cells infected with the Chlamydia-like organism Simkania negevensis (Sn). Simkania infected cells exhibited strong resistance to apoptosis induced by intrinsic stress or by the activation of cell death receptors. Apoptotic signaling was blocked upstream of mitochondria since Bax translocation, Bax and Bak oligomerisation and cytochrome c release were absent in these cells. Infected cells turned on pro-survival pathways like cellular Inhibitor of Apoptosis Protein 2 (cIAP-2) and the Akt/PI3K pathway. Blocking any of these inhibitory pathways sensitized infected host cell towards apoptosis induction, demonstrating their role in infection-induced apoptosis resistance. Our data support the hypothesis of evolutionary conserved signaling pathways to apoptosis resistance as common denominators in the order Chlamydiales.
authors.affiliation: Department of Microbiology, Biocenter, University of Würzburg, Würzburg, Germany.
authors.forename: Karthika
authors.initials: K
authors.lastname: Karunakaran
authors.forename: Adrian
authors.initials: A
authors.lastname: Mehlitz
authors.forename: Thomas
authors.initials: T
authors.lastname: Rudel
mesh_terms: D000818:Animals; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D061945:Caspase Inhibitors; D016923:Cell Death; D002695:Chlamydiales / Q000235:genetics* / Q000502:physiology*; D045304:Cytochromes c / Q000378:metabolism; D019143:Evolution, Molecular; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D015854:Up-Regulation; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D061945:Caspase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases; D051057:Proto-Oncogene Proteins c-akt