The inhibition of the apoptosis pathway by theCoxiella burnetiieffector protein CaeA requires the EK repetition motif, but is independent of survivin

Autor:	Anja Lührmann, Leonie Klingenbeck, Katharina Sobotta, Jan Schulze-Luehrmann, Vítor Borges, João Paulo Gomes, Christian Menge, Stephanie Bisle, Carsten Heydel
Rok vydání:	2016
Předmět:	0301 basic medicine Microbiology (medical) Survivin Amino Acid Motifs Immunology Surviving Apoptosis CHO Cells Microbiology Caspase 7 Inhibitor of Apoptosis Proteins Type IV Secretion Systems 03 medical and health sciences Cricetulus Bacterial Proteins Cricetinae Animals Humans Secretion Caspase Host cell nucleus Infecções Sistémicas e Zoonoses biology Effector Intrinsic apoptosis Type IV Secretion System Caspase 9 Cell biology HEK293 Cells Editorial CaeA 030104 developmental biology Infectious Diseases Coxiella burnetii Bacterial Pathogenesis Host cell cytoplasm biology.protein Parasitology
Zdroj:	Virulence. 7:400-412
ISSN:	2150-5608 2150-5594
Popis:	Coxiella burnetii is an obligate intracellular bacterium that causes Query (Q) fever, a zoonotic disease. It requires a functional type IV secretion system (T4SS) which translocate bacterial effector proteins into the host cell cytoplasm and thereby facilitates bacterial replication. To date, more than 130 effector proteins have been identified, but their functions remain largely unknown. Recently, we demonstrated that one of these proteins, CaeA (CBU1524) localized to the host cell nucleus and inhibited intrinsic apoptosis of HEK293 or CHO cells. In the present study we addressed the question whether CaeA also affects the extrinsic apoptosis pathway. Ectopic expression of CaeA reduced extrinsic apoptosis and prevented the cleavage of the executioner caspase 7, but did not impair the activation of initiator caspase 9. CaeA expression resulted in an up-regulation of survivin (an inhibitor of activated caspases), which, however, was not causal for the anti-apoptotic effect of CaeA. Comparing the sequence of CaeA from 25 different C. burnetii isolates we identified an EK (glutamic acid/ lysine) repetition motif as a site of high genetic variability. The EK motif of CaeA was essential for the anti-apoptotic activity of CaeA. From these data, we conclude that the C. burnetii effector protein CaeA interferes with the intrinsic and extrinsic apoptosis pathway. The process requires the EK repetition motif of CaeA, but is independent of the upregulated expression of survivin. This work was supported by the Deutsche Forschungsgemeinschaft (SFB796 project B8) to AL and by the ERA-NET PathoGenoMics 3rd call to AL and JPG.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8f847e4a0f79018bcb34b395f9e8bf97 https://doi.org/10.1080/21505594.2016.1139280 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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