Title

Premature apoptosis of Chlamydia-infected cells disrupts chlamydial development

ORCiD

David M. Ojcius: 0000-0003-1461-4495

Document Type

Article

Publication Title

Journal of Infectious Diseases

ISSN

0022-1899

Volume

198

Issue

10

DOI

10.1086/592755

First Page

1536

Last Page

1544

Publication Date

11-15-2008

Abstract

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 BimS 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, BimS 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.