Academic Journal
The Chlamydia trachomatis effector CT226 directly engages LRRFIP1 to recruit a multiprotein complex that limits inclusion size and progeny production.
| Τίτλος: | The Chlamydia trachomatis effector CT226 directly engages LRRFIP1 to recruit a multiprotein complex that limits inclusion size and progeny production. |
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| Συγγραφείς: | Elwell CA; University of California San Francisco, San Francisco, California, USA., Diallo A; University of California San Francisco, San Francisco, California, USA., Sixt BS; Duke University Medical Center, Durham, North Carolina, USA., Sherry J; University of California San Francisco, San Francisco, California, USA., Pha K; University of California San Francisco, San Francisco, California, USA., Valdivia RH; Duke University Medical Center, Durham, North Carolina, USA., Rosenberg O; University of California San Francisco, San Francisco, California, USA., Verba K; University of California San Francisco, San Francisco, California, USA., Engel J; University of California San Francisco, San Francisco, California, USA. |
| Πηγή: | MBio [mBio] 2026 Oct 14; Vol. 17 (10), pp. e0195326. Date of Electronic Publication: 2026 Sep 17. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, D.C. : American Society for Microbiology |
| Ιατρικοί όροι (MeSH): | Chlamydia trachomatis*/genetics , Chlamydia trachomatis*/metabolism , Chlamydia trachomatis*/growth & development , Bacterial Proteins*/metabolism , Bacterial Proteins*/genetics , Inclusion Bodies*/microbiology , Inclusion Bodies*/metabolism , Multiprotein Complexes*/metabolism , Membrane Proteins*/metabolism , Membrane Proteins*/genetics , Host-Pathogen Interactions*, Chlamydia Infections/microbiology ; Humans ; Protein Binding ; HeLa Cells |
| Περίληψη: | Chlamydia 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-mass 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 Chlamydia trachomatis infection. We show that CT226 is both necessary and sufficient to recruit the LRRFIP1/2:FLII:TMOD3 (LFT) complex to the inclusion membrane. In vitro reconstitution with purified proteins demonstrates that the predicted coiled-coil region of CT226 directly binds the N-terminal helix of LRRFIP1. Using in silico 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 C. trachomatis 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-host interaction at late timepoints of the C. trachomatis intracellular developmental cycle.IMPORTANCEChlamydia trachomatis 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-pathogen 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 Chlamydia intracellular development. These findings reveal how a bacterial effector can engage a host protein complex to influence the outcome of infection. |
| Competing Interests: | The authors declare no conflict of interest. |
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| Grant Information: | R56AI152526 National Institute of Allergy and Infectious Diseases; R01AI122747 National Institute of Allergy and Infectious Diseases |
| Contributed Indexing: | Keywords: Chlamydia trachomatis; Flightless; LRRFIP1; LRRFIP2; TMOD; alphafold; host–pathogen interactions; inclusion membrane protein; intracellular bacteria; microbial cell biology; vacuolar bacteria |
| Substance Nomenclature: | 0 (Bacterial Proteins) 0 (Multiprotein Complexes) 0 (Membrane Proteins) |
| Entry Date(s): | Date Created: 20260917 Date Completed: 20261014 Latest Revision: 20261029 |
| Update Code: | 20261029 |
| PubMed Central ID: | PMC13712786 |
| DOI: | 10.1128/mbio.01953-26 |
| PMID: | 42752221 |
| Βάση Δεδομένων: | MEDLINE |
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