{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:47:44Z","timestamp":1791985664233,"version":"4.4.0"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"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":["R56AI152526"],"award-info":[{"award-number":["R56AI152526"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI122747"],"award-info":[{"award-number":["R01AI122747"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,10,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                      species secrete a unique class of effector proteins termed inclusion membrane proteins (Incs) that are translocated into the inclusion membrane and reprogram host cell processes to support intracellular growth. Using affinity purification\u2013mass spectrometry, we previously identified an interaction between the early expressed Inc CT226 and a human multiprotein complex comprising leucine-rich repeat Flightless-I-interacting protein 1 (LRRFIP1), LRRFIP2, Flightless-I (FLII), and tropomodulin 3 (TMOD3). Here, we define the molecular basis and functional consequences of this interaction during\n                      <jats:italic toggle=\"yes\">Chlamydia trachomatis<\/jats:italic>\n                      infection. We show that CT226 is both necessary and sufficient to recruit the LRRFIP1\/2:FLII:TMOD3 (LFT) complex to the inclusion membrane.\n                      <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                      reconstitution with purified proteins demonstrates that the predicted coiled-coil region of CT226 directly binds the N-terminal helix of LRRFIP1. Using\n                      <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                      structural modeling with AlphaFold-Multimer coupled with mutational validation, we identify key residues that mediate an electrostatic CT226:LRRFIP1 interaction required for LFT recruitment to the inclusion. Unexpectedly, genetic disruption of CT226 or its interaction with the LFT complex results in modest increases in inclusion size and recovery of infectious progeny late in infection, demonstrating that the CT226:LFT interaction modulates\n                      <jats:italic toggle=\"yes\">C. trachomatis<\/jats:italic>\n                      developmental progression. Together, these findings establish the molecular basis of CT226-mediated recruitment of the LFT complex to the inclusion membrane and uncover a previously unrecognized role for this effector\u2013host interaction at late timepoints of the\n                      <jats:italic toggle=\"yes\">C. trachomatis<\/jats:italic>\n                      intracellular developmental cycle.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Chlamydia trachomatis<\/jats:italic>\n                        is a major cause of sexually transmitted infections and blindness worldwide. This bacterium survives by replicating inside host cells within a membrane-bound compartment, where it deploys specialized proteins to manipulate host processes. These proteins, known as inclusion membrane proteins (Incs), help organize the host\u2013pathogen interface, but the molecular mechanisms by which many Incs engage host factors remain poorly understood. Here, we show that the Inc protein CT226 recruits a host multiprotein complex to the bacterial compartment by directly binding one of its components. Using structural modeling and targeted mutations, we define the molecular interface required for this interaction. Disruption of CT226 or its ability to engage this host complex results in modest increases in inclusion size and production of infectious progeny, suggesting a role for the CT226:host interaction in regulating\n                        <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                        intracellular development. These findings reveal how a bacterial effector can engage a host protein complex to influence the outcome of infection.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01953-26","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T13:02:36Z","timestamp":1789650156000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["The\n                    <i>Chlamydia trachomatis<\/i>\n                    effector CT226 directly engages LRRFIP1 to recruit a multiprotein complex that limits inclusion size and progeny production"],"prefix":"10.1128","volume":"17","author":[{"given":"Cherilyn A.","family":"Elwell","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"University of California San Francisco","place":["San Francisco, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Diallo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"University of California San Francisco","place":["San Francisco, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5607-8902","authenticated-orcid":true,"given":"Barbara S.","family":"Sixt","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03njmea73","id-type":"ROR","asserted-by":"publisher"}],"name":"Duke University Medical Center","place":["Durham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Sherry","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"University of California San Francisco","place":["San Francisco, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khavong","family":"Pha","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"University of California San Francisco","place":["San Francisco, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0961-073X","authenticated-orcid":true,"given":"Raphael H.","family":"Valdivia","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03njmea73","id-type":"ROR","asserted-by":"publisher"}],"name":"Duke University Medical Center","place":["Durham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5736-4388","authenticated-orcid":true,"given":"Oren","family":"Rosenberg","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"University of California San Francisco","place":["San Francisco, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kliment","family":"Verba","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"University of California San Francisco","place":["San Francisco, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2168-9711","authenticated-orcid":true,"given":"Joanne","family":"Engel","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mz5j54","id-type":"ROR","asserted-by":"publisher"}],"name":"University of California San Francisco","place":["San Francisco, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Douglas and Bennett\u2019s principles and practice of infectious diseases","author":"Mandell GL","year":"2010","unstructured":"Mandell GL, Bennett JE, Mandell DR. 2010. 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