Abstract
We report here the identification of a bacterial protein capable of interacting with mammalian death receptors in vitro and in vivo. The protein is encoded in the genome of Chlamydia trachomatis and has homologues in other Chlamydia species. This protein, which we refer to as "Chlamydia protein associating with death domains" (CADD), induces apoptosis in a variety of mammalian cell lines when expressed by transient gene transfection. Apoptosis induction can be blocked by Caspase inhibitors, indicating that CADD triggers cell death by engaging the host apoptotic machinery. CADD interacts with death domains of tumor necrosis factor (TNF) family receptors TNFR1, Fas, DR4, and DR5 but not with the respective downstream adaptors. In infected epithelial cells, CADD is expressed late in the infectious cycle of C. trachomatis and co-localizes with Fas in the proximity of the inclusion body. The results suggest a role for CADD modulating the apoptosis pathways of cells infected, revealing a new mechanism of host-pathogen interaction.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Antigens, CD / metabolism
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Apoptosis
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Bacterial Proteins*
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COS Cells
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Cell Line
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Chlamydia / genetics
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Chlamydia muridarum / genetics
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Chlamydia trachomatis / metabolism*
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Cloning, Molecular
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DNA, Complementary / metabolism
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Fungal Proteins / chemistry*
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Fungal Proteins / genetics
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Fungal Proteins / metabolism*
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Glutathione Transferase / metabolism
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HeLa Cells
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Humans
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Immunoblotting
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Mice
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Mice, Inbred BALB C
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Microscopy, Fluorescence
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Molecular Sequence Data
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Plasmids / metabolism
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Precipitin Tests
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Protein Binding
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Protein Structure, Tertiary
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Receptors, TNF-Related Apoptosis-Inducing Ligand
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Receptors, Tumor Necrosis Factor / metabolism
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Receptors, Tumor Necrosis Factor, Type I
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Recombinant Fusion Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Homology, Amino Acid
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Species Specificity
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Transfection
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Tumor Cells, Cultured
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fas Receptor / metabolism
Substances
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Antigens, CD
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Bacterial Proteins
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CADD protein, Chlamydia trachomatis
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DNA, Complementary
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Fungal Proteins
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Receptors, TNF-Related Apoptosis-Inducing Ligand
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Type I
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Recombinant Fusion Proteins
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TNFRSF10A protein, human
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TNFRSF10B protein, human
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Tnfrsf10b protein, mouse
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fas Receptor
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Glutathione Transferase