This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lührmann, A. Articles by Roy, C. R. Search for Related Content PubMed PubMed Citation Articles by Lührmann, A. Articles by Roy, C. R.

 Previous Article  |  Next Article 

Infection and Immunity, November 2007, p. 5282-5289, Vol. 75, No. 11
0019-9567/07/$08.00+0     doi:10.1128/IAI.00863-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Coxiella burnetii Inhibits Activation of Host Cell Apoptosis through a Mechanism That Involves Preventing Cytochrome c Release from Mitochondria

Anja Lührmann and Craig R. Roy^*

Yale University School of Medicine, Section of Microbial Pathogenesis, 295 Congress Avenue, New Haven, Connecticut 06536

Received 24 June 2007/ Returned for modification 19 July 2007/ Accepted 8 August 2007

Coxiella burnetii is an obligate intracellular pathogen and the etiological agent of the human disease Q fever. C. burnetii infects mammalian cells and then remodels the membrane-bound compartment in which it resides into a unique lysosome-derived organelle that supports bacterial multiplication. To gain insight into the mechanisms by which C. burnetii is able to multiply intracellularly, we examined the ability of host cells to respond to signals that normally induce apoptosis. Our data show that mammalian cells infected with C. burnetii are resistant to apoptosis induced by staurosporine and UV light. C. burnetii infection prevented caspase 3/7 activation and limited fragmentation of the host cell nucleus in response to agonists that induce apoptosis. Inhibition of bacterial protein synthesis reduced the antiapoptotic effect that C. burnetii exerted on infected host cells. Inhibition of apoptosis in C. burnetii-infected cells did not correlate with the degradation of proapoptotic BH3-only proteins involved in activation of the intrinsic cell death pathway; however, cytochrome c release from mitochondria was diminished in cells infected with C. burnetii upon induction of apoptosis. These data indicate that C. burnetii can interfere with the intrinsic cell death pathway during infection by producing proteins that either directly or indirectly prevent release of cytochrome c from mitochondria. It is likely that inhibition of apoptosis by C. burnetii represents an important virulence property that allows this obligate intracellular pathogen to maintain host cell viability despite inducing stress that would normally activate the intrinsic death pathway.

---

* Corresponding author. Mailing address: Yale University School of Medicine, Section of Microbial Pathogenesis, 295 Congress Avenue, New Haven, CT 06536. Phone: (203) 737-2408. Fax: (203) 737-2630. E-mail: craig.roy{at}yale.edu

Published ahead of print on 20 August 2007.

Editor: R. P. Morrison

---

Infection and Immunity, November 2007, p. 5282-5289, Vol. 75, No. 11
0019-9567/07/$08.00+0     doi:10.1128/IAI.00863-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Voth, D. E., Howe, D., Beare, P. A., Vogel, J. P., Unsworth, N., Samuel, J. E., Heinzen, R. A. (2009). The Coxiella burnetii Ankyrin Repeat Domain-Containing Protein Family Is Heterogeneous, with C-Terminal Truncations That Influence Dot/Icm-Mediated Secretion. J. Bacteriol. 191: 4232-4242 [Abstract] [Full Text]  
• Voth, D. E., Heinzen, R. A. (2009). Sustained Activation of Akt and Erk1/2 Is Required for Coxiella burnetii Antiapoptotic Activity. Infect. Immun. 77: 205-213 [Abstract] [Full Text]