Degradation of the Proapoptotic Proteins Bik, Puma, and Bim with Bcl-2 Domain 3 Homology in Chlamydia trachomatis -Infected Cells

Abstract

We have previously correlated Chlamydia trachomatis antiapoptotic activity with the blockade of mitochondrial cytochrome c release and the inhibition of Bax and Bak activation. We now report that C. trachomatis infection leads to degradation of Bik, Puma, and Bim, three upstream proapoptotic BH3-only proteins of the Bcl-2 family that can transmit death signals to mitochondria by inhibiting the Bcl-2 antiapoptotic proteins and/or activating the Bcl-2 proapoptotic members, such as Bax and Bak. This observation has provided new information on the chlamydial antiapoptosis mechanisms.

Chlamydia trachomatis Infection Induces Cleavage of the Mitotic Cyclin B1

“…Degradation of the transcription factors RFX5 and USF-1 during C. trachomatis infection has been shown to reduce expression of the major histocompatibility complex genes and thereby serve as a putative immune evasion strategy (45,46). Likewise, degradation of the BH3 (Bcl-2 homology domain 3) family of proapoptotic factors protects C. trachomatis-infected cells from programmed cell death (8,12,41). Finally, C. trachomatis also cleaves host keratin 8, a subunit of intermediate filaments (9).…”

“…In addition to cyclin B1, several other host proteins have been reported to undergo proteolytic cleavage in response to C. trachomatis infection (8,9,12,41,45,46). Degradation of the transcription factors RFX5 and USF-1 during C. trachomatis infection has been shown to reduce expression of the major histocompatibility complex genes and thereby serve as a putative immune evasion strategy (45,46).…”

“…Most importantly, the cell must remain viable during infection. C. trachomatis has been shown to promote host cell survival by actively inhibiting the mitochondrial pathway of apoptosis, in part by triggering proteasomal degradation of proapoptotic factors within the cell (8,(10)(11)(12)41). Even host cell division may pose challenges to C. trachomatis replication, since important nutrients may be consumed as the cell divides.…”

Coxiella burnetii modulates Beclin 1 and Bcl-2, preventing host cell apoptosis to generate a persistent bacterial infection

“…For example, Chlamydia trachomatis and Toxoplasma gondii are known to possess anti-apoptotic activity. 40,41 Recently, it has been shown that a substrate (SidF) of the Dot/Icm T4SS is involved in preventing apoptosis in infected cells with Legionella pneumophila. Apparently, SidF would abolish the activities of two proapoptotic proteins members of the Bcl-2 family: BNIP3 and Bcl-rambo.…”

Chlamydial Intracellular Survival Strategies

“…Chlamydia interferes with multiple proapoptotic pathways as well as potential necrotic cell death to guarantee survival within host cells Fischer et al 2001;Rajalingam et al 2001;Yu et al 2010). A prominent mechanism for preventing cell death includes CPAFmediated degradation of the proapoptotic BH3-only proteins Bad, Bim, and Puma (Fischer et al 2004;Dong et al 2005;Ying et al 2005;Pirbhai et al 2006). This activity is proposed to be responsible for the reduced activation of Bax and Bak and subsequent block in cytochrome c release observed during infection Fischer et al 2004;Xiao et al 2004).…”