{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:51:52Z","timestamp":1753883512110,"version":"3.41.2"},"reference-count":58,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21AI148999, R01AI139242"],"award-info":[{"award-number":["R21AI148999, R01AI139242"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              <jats:italic>Chlamydia trachomatis<\/jats:italic>\n              (\n              <jats:italic>Ct<\/jats:italic>\n              ) is an obligate, intracellular Gram-negative bacteria and the leading bacterial sexually transmitted infection in the United States.\n              <jats:italic>Chlamydia<\/jats:italic>\n              manipulates the host cell biology using various secreted bacterial effectors during its intracellular development. The early effector\n              <jats:italic>t<\/jats:italic>\n              ranslocated\n              <jats:italic>a<\/jats:italic>\n              ctin-\n              <jats:italic>r<\/jats:italic>\n              ecruiting\n              <jats:italic>p<\/jats:italic>\n              hosphoprotein (Tarp), important for\n              <jats:italic>Chlamydia<\/jats:italic>\n              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\n              <jats:italic>Chlamydia<\/jats:italic>\n              spp. To address this, we use\n              <jats:italic>Drosophila melanogaster<\/jats:italic>\n              as an\n              <jats:italic>in vivo<\/jats:italic>\n              cell biology platform to study N-Tarp-host interactions. Transgenic expression of N-Tarp in\n              <jats:italic>Drosophila<\/jats:italic>\n              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\n              <jats:italic>CycE<\/jats:italic>\n              and\n              <jats:italic>Drosophila inhibitor of apoptosis 1 (Diap1)<\/jats:italic>\n              . Thus, we provide 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:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              The survival of obligate intracellular bacteria like\n              <jats:italic>Chlamydia<\/jats:italic>\n              depends on the survival of the host cell itself. It is not surprising that\n              <jats:italic>Chlamydia<\/jats:italic>\n              -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\n              <jats:italic>Ct<\/jats:italic>\n              early effector Tarp can alter Hippo signaling in vivo. Only recently implicated in\n              <jats:italic>Chlamydia<\/jats:italic>\n              infection, the Hippo pathway is known to promote cell survival. Our findings illuminate one possible mechanism for\n              <jats:italic>Chlamydia<\/jats:italic>\n              to promote host cell survival during infection. We further demonstrate the utility of\n              <jats:italic>Drosophila melanogaster<\/jats:italic>\n              as a tool in the study of effector function.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.02596-24","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T14:03:11Z","timestamp":1741615391000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","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":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8253-4468","authenticated-orcid":true,"given":"George F.","family":"Aranjuez","sequence":"first","affiliation":[{"name":"Immunity and Pathogenesis Division, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida","place":["Orlando, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Om","family":"Patel","sequence":"additional","affiliation":[{"name":"Immunity and Pathogenesis Division, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida","place":["Orlando, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dev","family":"Patel","sequence":"additional","affiliation":[{"name":"Immunity and Pathogenesis Division, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida","place":["Orlando, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Travis J.","family":"Jewett","sequence":"additional","affiliation":[{"name":"Immunity and Pathogenesis Division, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida","place":["Orlando, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","unstructured":"Centers for Disease Control and Prevention. 2024. Sexually transmitted infections surveillance 2022. US Department of Health and Human Services. Available from: https:\/\/www.cdc.gov\/std\/statistics\/2022\/default.htm"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2015.08.004"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00917-13"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000997"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2016.00084"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00841-19"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.7.3793-3803.2002"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402829101"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2016.00107"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603044103"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01768-12"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008878"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02861-20"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1232391"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/gbe\/evad147"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.04.089"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00515-10"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.811407"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2021.05.057"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1924-3"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2022.04.001"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2010.09.011"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01191-9"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3458"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.24.110707.175242"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a019224"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2008.02.034"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047173"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.09.012"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2013449117"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2012.03.003"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-34674-y"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.07.013"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2006.08.057"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.070367"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1339"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201809121"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-018-0086-y"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.7.3860-3868.2005"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200909095"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2008.00515.x"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040402"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.9.5470-5474.2004"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.4.487"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2022.03.012"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a008730"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1098420"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.08.004"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00085-23"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02184-19"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","unstructured":"Wu SC Grace M Munger K. 2023. The HPV8 E6 protein targets the Hippo and Wnt signaling pathways as part of its arsenal to restrain keratinocyte differentiation. Microbiology. doi:10.1101\/2023.06.22.546184","DOI":"10.1101\/2023.06.22.546184"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-018-0962-5"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.03033"},{"key":"e_1_3_3_55_2","first-page":"610","article-title":"The HIPPO pathway in gynecological malignancies","volume":"10","author":"Wang D","year":"2020","unstructured":"Wang D, He J, Dong J, Meyer TF, Xu T. 2020. The HIPPO pathway in gynecological malignancies. Am J Cancer Res 10:610\u2013629.","journal-title":"Am J Cancer Res"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.118.2.401"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/iyad211"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.12.012"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.02596-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.02596-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T13:16:17Z","timestamp":1743513377000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.02596-24"}},"subtitle":[],"editor":[{"given":"Stacey D.","family":"Gilk","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":58,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1128\/spectrum.02596-24"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.02596-24","relation":{},"ISSN":["2165-0497"],"issn-type":[{"type":"electronic","value":"2165-0497"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"2024-10-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02596-24"}}