{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:55:40Z","timestamp":1782280540765,"version":"3.54.5"},"posted":{"date-parts":[[2024,9,12]]},"group-title":"Microbiology","reference-count":57,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T00:00:00Z","timestamp":1726099200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,9,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:italic>Chlamydia trachomatis<\/jats:italic>\n                  is an obligate, intracellular Gram-negative bacteria and the leading bacterial STI in the United States.\n                  <jats:italic>Chlamydia<\/jats:italic>\n                  \u2019s developmental cycle involves host cell entry, replication within a parasitophorous vacuole called an inclusion, and induction of host cell lysis to release new infectious particles. During development,\n                  <jats:italic>Chlamydia<\/jats:italic>\n                  manipulates the host cell biology using various secreted bacterial effectors. The early effector Tarp is important for\n                  <jats:italic>Chlamydia<\/jats:italic>\n                  entry via its well-characterized C-terminal region which can polymerize and bundle F-actin. In contrast, not much is known about the function of Tarp\u2019s N-terminus (N-Tarp), though this N-terminal region is present in many\n                  <jats:italic>Chlamydia<\/jats:italic>\n                  species. To address this, we use\n                  <jats:italic>Drosophila melanogaster<\/jats:italic>\n                  as an in vivo cell biology platform to study N-Tarp-host interactions.\n                  <jats:italic>Drosophila<\/jats:italic>\n                  development is well-characterized such that developmental phenotypes can be traced back to the perturbed molecular pathway. Transgenic expression of N-Tarp in\n                  <jats:italic>Drosophila<\/jats:italic>\n                  tissues results in phenotypes consistent with altered host Hippo signaling. The Salvador-Warts-Hippo pathway is a conserved signaling cascade that regulates host cell proliferation and survival during normal animal development. We studied 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\n                  <jats:italic>CycE<\/jats:italic>\n                  and\n                  <jats:italic>Diap1<\/jats:italic>\n                  . Thus, we provide the first evidence that the N-terminal region of the\n                  <jats:italic>Chlamydia<\/jats:italic>\n                  effector Tarp is sufficient to alter host Hippo signaling and acts upstream of the co-activator Yorkie.\n                  <jats:italic>Chlamydia<\/jats:italic>\n                  alters host cell apoptosis during infection, though the exact mechanism remains unknown. Our findings implicate the N-terminal region of Tarp as a way to manipulate the host Hippo signaling pathway, which directly influences cell survival.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Author Summary<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Chlamydia<\/jats:italic>\n                    -infected cells are known to be resistant to apoptotic cues, facilitating the successful completion of its infectious cycle. The exact molecular mechanism of apoptosis inhibition is unknown and the search for secreted effectors that mediate this is ongoing. We developed\n                    <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    as a platform to study\n                    <jats:italic>Chlamydia<\/jats:italic>\n                    effector function in vivo without the confounding influence of actual infection. Genetic tools make it easy to generate transgenic flies and express bacterial effectors of interest in any tissue, allowing for discovery of new function based on observed developmental phenotypes. Using this platform, we showed that the N-terminal region of the early effector Tarp intersects with the host Hippo pathway, causing upregulation of Hippo target genes. Interestingly, the Hippo pathway directly controls the expression of potent inhibitors of apoptosis (IAPs). Our findings support a possible link between a secreted effector, Tarp and its N-terminal region, and the Hippo pathway to block apoptosis during infection.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.09.12.612603","type":"posted-content","created":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T00:45:20Z","timestamp":1726188320000},"source":"Crossref","is-referenced-by-count":0,"title":["The N-terminus of the\n                  <i>Chlamydia trachomatis<\/i>\n                  effector Tarp engages the host Hippo pathway"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8253-4468","authenticated-orcid":false,"given":"George F","family":"Aranjuez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Om","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dev","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis J","family":"Jewett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024091522291396000_2024.09.12.612603v1.1","unstructured":"Centers for Disease Control and Prevention. 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