Article thumbnail

Evolutionary Conservation of Infection-Induced Cell Death Inhibition among Chlamydiales

By Karthika Karunakaran, Adrian Mehlitz and Thomas Rudel


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

Topics: Research Article
Publisher: Public Library of Science
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. (2000). 14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation.
  2. (2006). 7: key mediators of mitochondrial events of apoptosis.
  3. (1994). A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002).
  4. (2003). Akt activity in endometrial cancer cells: regulation of cell survival through cIAP-1.
  5. (1997). Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery.
  6. (1999). Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor.
  7. (2005). Akt-dependent transformation: there is more to growth than just surviving.
  8. (2001). alpha-Toxin is a mediator of Staphylococcus aureus-induced cell death and activates caspases via the intrinsic death pathway independently of death receptor signaling.
  9. (2004). Amoebae-resisting bacteria isolated from human nasal swabs by amoebal coculture. Emerging infectious diseases 10:
  10. (1997). Apoptosis in bacterial pathogenesis.
  11. (2009). Apoptosis resistance in Chlamydia-infected cells: a fate worse than death?
  12. (2005). Broad degradation of proapoptotic proteins with the conserved Bcl-2 homology domain 3 during infection with Chlamydia trachomatis.
  13. (2009). Caspases and kinases in a death grip.
  14. (1999). Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms.
  15. (2001). Characterization of antiapoptotic activities of Chlamydia pneumoniae in human cells.
  16. (2004). Chlamydia inhibit host cell apoptosis by degradation of proapoptotic BH3-only proteins.
  17. (2001). Chlamydia trachomatis-induced apoptosis occurs in uninfected McCoy cells late in the developmental cycle and is regulated by the intracellular redox state.
  18. (2010). Chlamydia trachomatisinfected host cells resist dsRNA-induced apoptosis.
  19. (2009). cIAP-1 controls innate immunity to C. pneumoniae pulmonary infection.
  20. (2005). Degradation of the proapoptotic proteins Bik,
  21. (1993). Description and partial characterization of a new Chlamydia-like microorganism.
  22. (2001). Epithelial cells infected with Chlamydophila pneumoniae (Chlamydia pneumoniae) are resistant to apoptosis.
  23. (2010). Fastidious intracellular bacteria as causal agents of community-acquired pneumonia.
  24. (1998). High prevalence of ‘‘Simkania Z,’’ a novel Chlamydia-like bacterium, in infants with acute bronchiolitis.
  25. (2003). High rate of Simkania negevensis among Canadian inuit infants hospitalized with lower respiratory tract infections.
  26. (2009). Host cell death machinery as a target for bacterial pathogens.
  27. (1999). How BAD phosphorylation is good for survival.
  28. (2006). IAPIAP complexes required for apoptosis resistance of C. trachomatis-infected cells.
  29. (2005). IAPs, RINGs and ubiquitylation.
  30. (2010). IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer.
  31. (2002). Identification of MEK- and phosphoinositide 3-kinase-dependent signalling as essential events during Chlamydia pneumoniae invasion of HEp2 cells.
  32. (1998). Inhibition of apoptosis in chlamydia-infected cells: blockade of mitochondrial cytochrome c release and caspase activation.
  33. (2008). Mcl1 is a key regulator of apoptosis resistance in Chlamydia trachomatis-infected cells.
  34. (2003). Mechanism of XIAP-mediated inhibition of caspase-9.
  35. (2009). Mitochondrial cell death effectors.
  36. (2000). Mitrochondrial control of cell death.
  37. (1999). NF-kappa B is a target of AKT in antiapoptotic PDGF signalling.
  38. (1998). NFkappa B-dependent inhibition of apoptosis is essential for host cellsurvival during Rickettsia rickettsii infection.
  39. (2006). NFkappaB and inhibitor of apoptosis proteins are required for apoptosis resistance of epithelial cells persistently infected with Chlamydophila pneumoniae.
  40. (1997). Nonionic detergents induce dimerization among members of the Bcl-2 family.
  41. (2008). Novel Parachlamydia acanthamoebae quantification method based on coculture with amoebae. Applied and environmental microbiology 74:
  42. (2003). Parachlamydia acanthamoebae enters and multiplies within human macrophages and induces their apoptosis [corrected]. Infection and immunity 71:
  43. (2009). Parachlamydia acanthamoebae, an emerging agent of pneumonia.
  44. (2006). Pathogenic potential of novel Chlamydiae and diagnostic approaches to infections due to these obligate intracellular bacteria.
  45. (1997). Porath A
  46. (2004). Protection against CD95-induced apoptosis by chlamydial infection at a mitochondrial step.
  47. (2006). Recruitment of BAD by the Chlamydia trachomatis vacuole correlates with host-cell survival.
  48. (1998). Regulation of cell-death protease caspase-9 by phosphorylation.
  49. (1996). Salmonella typhimurium invasion induces apoptosis in infected macrophages.
  50. (2002). Serological evidence of acute infection with the Chlamydia-like microorganism Simkania negevensis (Z) in acute exacerbation of chronic obstructive pulmonary disease.
  51. (1992). Shigella flexneri induces apoptosis in infected macrophages.
  52. (2007). Simkania negevensis in bronchoalveolar lavage of lung transplant recipients: a possible association with acute rejection.
  53. (2009). Simkania negevensis infection among Brazilian children hospitalized with community-acquired pneumonia.
  54. (2008). Simkania negevensis may be a true cause of community acquired pneumonia in children.
  55. (1999). Simkania negevensis strain ZT: growth, antigenic and genome characteristics.
  56. (2008). Strasser A
  57. (2000). Targeting of the pro-apoptotic VDAC-like porin (PorB) of Neisseria gonorrhoeae to mitochondria of infected cells.
  58. (2002). The growth cycle of Simkania negevensis.
  59. (1997). The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis.
  60. (1999). Tumor necrosis factor receptor and Fas signaling mechanisms.
  61. (2007). Type III secretion a la Chlamydia. Trends in microbiology 15:
  62. (2005). XIAP inhibits caspase-3 and -7 using two binding sites: evolutionarily conserved mechanism of IAPs.