The N-terminus of the Chlamydia trachomatis effector Tarp engages the host Hippo pathway
ABSTRACT Chlamydia trachomatis (Ct) is an obligate, intracellular Gram-negative bacteria and the leading bacterial sexually transmitted infection in the United States. Chlamydia manipulates the host cell biology using various secreted bacterial effectors during its intracellular development. The ear...
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American Society for Microbiology
2025-04-01
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| Series: | Microbiology Spectrum |
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| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.02596-24 |
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| author | George F. Aranjuez Om Patel Dev Patel Travis J. Jewett |
| author_facet | George F. Aranjuez Om Patel Dev Patel Travis J. Jewett |
| author_sort | George F. Aranjuez |
| collection | DOAJ |
| description | ABSTRACT Chlamydia trachomatis (Ct) is an obligate, intracellular Gram-negative bacteria and the leading bacterial sexually transmitted infection in the United States. Chlamydia manipulates the host cell biology using various secreted bacterial effectors during its intracellular development. The early effector translocated actin-recruiting phosphoprotein (Tarp), important for Chlamydia entry, has a well-characterized C-terminal region which can polymerize and bundle F-actin. In contrast, not much is known about the function of the N-terminus of Tarp (N-Tarp), though present in many Chlamydia spp. To address this, we use Drosophila melanogaster as an in vivo cell biology platform to study N-Tarp-host interactions. Transgenic expression of N-Tarp in Drosophila results in developmental phenotypes consistent with altered host Salvador-Warts-Hippo signaling, a conserved signaling cascade that regulates host cell proliferation and survival. We studied the N-Tarp function in larval imaginal wing discs, which are sensitive to perturbations in Hippo signaling. N-Tarp causes wing disc overgrowth and a concomitant increase in adult wing size, phenocopying overexpression of the Hippo co-activator Yorkie. N-Tarp also causes upregulation of Hippo target genes. Last, N-Tarp-induced phenotypes can be rescued by reducing the levels of Yorkie or the Hippo target genes CycE and Drosophila inhibitor of apoptosis 1 (Diap1). Thus, we provide evidence that the N-terminal region of the Chlamydia effector Tarp is sufficient to alter host Hippo signaling and acts upstream of the co-activator Yorkie.IMPORTANCEThe survival of obligate intracellular bacteria like Chlamydia depends on the survival of the host cell itself. It is not surprising that Chlamydia-infected cells are resistant to cell death, though the exact molecular mechanism is largely unknown. Here, we establish that the N-terminal region of the well-known Ct early effector Tarp can alter Hippo signaling in vivo. Only recently implicated in Chlamydia infection, the Hippo pathway is known to promote cell survival. Our findings illuminate one possible mechanism for Chlamydia to promote host cell survival during infection. We further demonstrate the utility of Drosophila melanogaster as a tool in the study of effector function. |
| format | Article |
| id | doaj-art-2fae8746e3d2441ba56b9311fb5d2c7e |
| institution | DOAJ |
| issn | 2165-0497 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | American Society for Microbiology |
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| series | Microbiology Spectrum |
| spelling | doaj-art-2fae8746e3d2441ba56b9311fb5d2c7e2025-08-20T03:06:51ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-04-0113410.1128/spectrum.02596-24The N-terminus of the Chlamydia trachomatis effector Tarp engages the host Hippo pathwayGeorge F. Aranjuez0Om Patel1Dev Patel2Travis J. Jewett3Immunity and Pathogenesis Division, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, USAImmunity and Pathogenesis Division, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, USAImmunity and Pathogenesis Division, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, USAImmunity and Pathogenesis Division, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, USAABSTRACT Chlamydia trachomatis (Ct) is an obligate, intracellular Gram-negative bacteria and the leading bacterial sexually transmitted infection in the United States. Chlamydia manipulates the host cell biology using various secreted bacterial effectors during its intracellular development. The early effector translocated actin-recruiting phosphoprotein (Tarp), important for Chlamydia entry, has a well-characterized C-terminal region which can polymerize and bundle F-actin. In contrast, not much is known about the function of the N-terminus of Tarp (N-Tarp), though present in many Chlamydia spp. To address this, we use Drosophila melanogaster as an in vivo cell biology platform to study N-Tarp-host interactions. Transgenic expression of N-Tarp in Drosophila results in developmental phenotypes consistent with altered host Salvador-Warts-Hippo signaling, a conserved signaling cascade that regulates host cell proliferation and survival. We studied the N-Tarp function in larval imaginal wing discs, which are sensitive to perturbations in Hippo signaling. N-Tarp causes wing disc overgrowth and a concomitant increase in adult wing size, phenocopying overexpression of the Hippo co-activator Yorkie. N-Tarp also causes upregulation of Hippo target genes. Last, N-Tarp-induced phenotypes can be rescued by reducing the levels of Yorkie or the Hippo target genes CycE and Drosophila inhibitor of apoptosis 1 (Diap1). Thus, we provide evidence that the N-terminal region of the Chlamydia effector Tarp is sufficient to alter host Hippo signaling and acts upstream of the co-activator Yorkie.IMPORTANCEThe survival of obligate intracellular bacteria like Chlamydia depends on the survival of the host cell itself. It is not surprising that Chlamydia-infected cells are resistant to cell death, though the exact molecular mechanism is largely unknown. Here, we establish that the N-terminal region of the well-known Ct early effector Tarp can alter Hippo signaling in vivo. Only recently implicated in Chlamydia infection, the Hippo pathway is known to promote cell survival. Our findings illuminate one possible mechanism for Chlamydia to promote host cell survival during infection. We further demonstrate the utility of Drosophila melanogaster as a tool in the study of effector function.https://journals.asm.org/doi/10.1128/spectrum.02596-24Chlamydia trachomatiseffector functionshost-pathogen interactionsDrosophilacell signaling |
| spellingShingle | George F. Aranjuez Om Patel Dev Patel Travis J. Jewett The N-terminus of the Chlamydia trachomatis effector Tarp engages the host Hippo pathway Microbiology Spectrum Chlamydia trachomatis effector functions host-pathogen interactions Drosophila cell signaling |
| title | The N-terminus of the Chlamydia trachomatis effector Tarp engages the host Hippo pathway |
| title_full | The N-terminus of the Chlamydia trachomatis effector Tarp engages the host Hippo pathway |
| title_fullStr | The N-terminus of the Chlamydia trachomatis effector Tarp engages the host Hippo pathway |
| title_full_unstemmed | The N-terminus of the Chlamydia trachomatis effector Tarp engages the host Hippo pathway |
| title_short | The N-terminus of the Chlamydia trachomatis effector Tarp engages the host Hippo pathway |
| title_sort | n terminus of the chlamydia trachomatis effector tarp engages the host hippo pathway |
| topic | Chlamydia trachomatis effector functions host-pathogen interactions Drosophila cell signaling |
| url | https://journals.asm.org/doi/10.1128/spectrum.02596-24 |
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