Structure of the Chlamydia Protein CADD Reveals a Redox Enzyme That Modulates Host Cell Apoptosis

Schwarzenbacher, Robert; Stenner, Frank; Liewen, Heike; Robinson, Howard; Yuan, Hua; Bossy‐Wetzel, Ella; Reed, John C.; Liddington, Robert

doi:10.1074/jbc.m401268200

Cited by 63 publications

(75 citation statements)

References 24 publications

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“…CADD shares homology with the death domains of tumor necrosis factor family receptors and induces apoptosis when transiently transfected to noninfected cells (36). Although it is not known at present whether CADD is the dominant protein governing apoptosis, a recent study reporting the crystal structure of this protein (35) demonstrated its capability to induce in vivo cell death of HeLa cells. Both catalytic activity and death domain binding were found to be required for its complete biological function.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Response Patterns ofChlamydophila psittaciin Different In Vitro Models of Persistent Infection

Goellner¹,

Schubert²,

Liebler-Tenorio

et al. 2006

Infect Immun

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The obligatory intracellular bacterium Chlamydophila psittaci is the causative agent of psittacosis in birds and humans. The capability of this zoonotic pathogen to develop a persistent phase is likely to play a role in chronicity of infections, as well as in failure of antibiotic therapy and immunoprophylaxis. To elucidate three different in vitro models for transition of C. psittaci to persistence (iron depletion, penicillin G treatment, and gamma interferon [IFN-␥] exposure), a set of 27 genes was examined by mRNA expression analysis using quantitative real-time PCR. While the phenotypical characteristics were the same as in other chlamydiae, i.e., aberrant morphology of reticulate bodies, loss of cultivability, and rescue of infectivity upon removal of inducers, the transcriptional response of C. psittaci to persistence-inducing factors included several new and distinctive features. Consistent downregulation of membrane proteins, chlamydial sigma factors, cell division protein, and reticulate body-elementary body differentiation proteins from 24 h postinfection onward proved to be a general feature of C. psittaci persistence. However, other genes displayed considerable variations in response patterns from one model to another, which suggests that there is no persistence model per se. In contrast to results for Chlamydia trachomatis, late shutdown of essential genes in C. psittaci was more comprehensive with IFN-␥-induced persistence, which is probably due to the absence of a functional tryptophan synthesis operon.

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Section: Discussionmentioning

confidence: 99%

Transcriptional Response Patterns ofChlamydophila psittaciin Different In Vitro Models of Persistent Infection

Goellner¹,

Schubert²,

Liebler-Tenorio

et al. 2006

Infect Immun

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“…C. pneumoniae and C. muridarum contain open reading frames encoding hypothetical proteins exhibiting sequence similarity and predicted structural homology to CADD (44,45).…”

Section: Discussionmentioning

confidence: 99%

Chlamydia pneumoniaeAugments the Oxidized Low-Density Lipoprotein-Induced Death of Mouse Macrophages by a Caspase-Independent Pathway

Yaraei¹,

Campbell²,

Zhu

et al. 2005

Infect Immun

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Chlamydia pneumoniae is a common respiratory pathogen that is associated with an increased risk of cardiovascular disease. However, the mechanisms by which C. pneumoniae contributes to cardiovascular disease have not been determined yet. C. pneumoniae infection may accelerate the death of cells within atherosclerotic lesions and contribute to the formation of unstable lesions. To test this hypothesis, the impact of C. pneumoniae infection on the death of lipid-loaded mouse macrophages was investigated. It was observed that RAW 264.7 cells are highly susceptible to the toxic effects of oxidized low-density lipoprotein (LDL) and exhibit markers of cell death within 24 h of treatment with as little as 5 g/ml oxidized LDL. Subsequent infection with either live C. pneumoniae or heat-killed or UV-inactivated C. pneumoniae at a low multiplicity of infection for 24 to 72 h stimulated both additional binding of annexin V and the uptake of propidium iodide. Thus, C. pneumoniae augments the effects of oxidized LDL on cell death independent of a sustained infection. However, unlike oxidized LDL, C. pneumoniae infection does not activate caspase 3 or induce formation of the mitochondrial transition pore or the fragmentation of DNA, all of which are classical markers of apoptosis. Furthermore, primary bone marrow macrophages isolated from mice deficient in Toll-like receptor 2 (TLR-2) but not TLR-4 are resistant to C. pneumoniae-induced death. These data suggest that C. pneumoniae kills cells by a caspase-independent pathway and that the process is potentially mediated by activation of TLR-2.

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“…1D), monitoring the m/z ratios corresponding to [M ϩ 2H] 2ϩ and [M ϩ 3H] 3ϩ ions of both peptides. These analyses failed to show any reliable fragmentation compatible with ClpC(7-15) or ClpC (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17).…”

Section: One Clpc-derived Ligand Distinct From the Predicted T-cell Ementioning

confidence: 99%

“…1A). EGFP-ClpC fusion proteins were expressed in C1R-B*27:05 cells in order to detect endogenously processed HLA-B27 ligands from this protein, including a predicted T-cell epitope, ClpC (7)(8)(9)(10)(11)(12)(13)(14)(15). Our initial attempts to express the whole ClpC protein using full-length cDNA failed to generate stable C1R transfectants.…”

Section: Expression Of Chlamydial Clpc Fusion Proteins-clpc Is Anmentioning

confidence: 99%

Novel HLA-B27-restricted Epitopes from Chlamydia trachomatis Generated upon Endogenous Processing of Bacterial Proteins Suggest a Role of Molecular Mimicry in Reactive Arthritis

Alvarez-Navarro

Cragnolini

Santos

et al. 2013

Journal of Biological Chemistry

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Background:Reactive arthritis is an HLA-B27-associated disease triggered by Chlamydia trachomatis. Results: Three chlamydial peptides endogenously presented by HLA-B27 were identified. All were homologous to humanderived sequences, and one showed conformational similarity to a self-derived HLA-B27 ligand. Conclusion: Molecular mimicry between chlamydial and self-derived HLA-B27 ligands is not uncommon. Significance: Molecular mimicry may contribute to the pathology of reactive arthritis.

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Structure of the Chlamydia Protein CADD Reveals a Redox Enzyme That Modulates Host Cell Apoptosis

Cited by 63 publications

References 24 publications

Transcriptional Response Patterns ofChlamydophila psittaciin Different In Vitro Models of Persistent Infection

Transcriptional Response Patterns ofChlamydophila psittaciin Different In Vitro Models of Persistent Infection

Chlamydia pneumoniaeAugments the Oxidized Low-Density Lipoprotein-Induced Death of Mouse Macrophages by a Caspase-Independent Pathway

Novel HLA-B27-restricted Epitopes from Chlamydia trachomatis Generated upon Endogenous Processing of Bacterial Proteins Suggest a Role of Molecular Mimicry in Reactive Arthritis

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