Premature apoptosis of Chlamydia-infected cells disrupts chlamydial development.
The obligate intracellular development of Chlamydia suggests that the bacteria should be vulnerable to premature host cell apoptosis, but because Chlamydia-infected cells are apoptosis resistant, this has never been able to be tested. We have devised a system to circumvent the apoptotic block imposed by chlamydial infection. When the proapoptotic protein Bim(S) was experimentally induced, epithelial cells underwent apoptosis that was not blocked by chlamydial infection. Apoptosis during the developmental cycle prevented the generation of infectious bacteria and caused transcriptional changes of bacterial genes and loss of intracellular ATP. Intriguingly, although apoptosis resulted in destruction of host cell structures and of the Chlamydia inclusion, and prevented generation of elementary bodies, Bim(S) induction in the presence of a caspase inhibitor allowed differentiation into morphologically normal but noninfectious elementary bodies. These data show that chlamydial infection renders host cells apoptosis resistant at a premitochondrial step and demonstrate the consequences of premature apoptosis for development of the bacteria.
Ying
Songmin
S
Institute for Medical Microbiology, Immunology and Hygiene, Technical University Munich, Germany.
Pettengill
Matthew
M
Latham
E Ray
ER
Walch
Axel
A
Ojcius
David M
DM
Häcker
Georg
G
D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D020169:Caspases / Q000378:metabolism; D002690:Chlamydia Infections / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D002692:Chlamydia trachomatis / Q000254:growth & development / Q000502:physiology* / Q000648:ultrastructure; D004847:Epithelial Cells / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D000255:Adenosine Triphosphate; D020169:Caspases