{"doi":"10.1101/2022.02.18.481055","title":"The <i>Chlamydia</i> protein CpoS modulates the inclusion microenvironment and restricts the interferon response by acting on Rab35","abstract":"ABSTRACT The obligate intracellular bacterium Chlamydia trachomatis inserts into the membrane of its vacuole (the inclusion) a family of poorly characterized Inc proteins. While the Inc CpoS was recently revealed as a critical suppressor of host cellular immune surveillance, the underlying mechanism remained unknown. By complementing a cpoS mutant with modified variants of CpoS, we found that CpoS blocks distinct cellular defense responses through distinct mechanisms. Specifically, we show that the ability of CpoS to interact with Rab GTPases is not only instrumental to its ability to mediate lipid transport to the inclusion, but also key to CpoS-mediated inhibition of type I interferon responses. Indeed, depletion of Rab35 can phenocopy the respective defect of the cpoS mutant. Unexpectedly, we found that CpoS is also essential for the formation of inclusion microdomains that control the spatial organization of multiple Incs involved in signaling and modulation of the host cellular cytoskeleton. Overall, our findings highlight the modulation of membrane trafficking as a pathogenic immune evasion strategy and the role of Inc-Inc interactions in shaping the inclusion microenvironment.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":297481,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9585,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":986066,"name":"Lana H. Jachmann","orcid":null,"position":1,"is_corresponding":false},{"id":985519,"name":"Lucía Peña‐Pérez","orcid":"0000-0002-5044-7754","position":2,"is_corresponding":false},{"id":257793,"name":"Oliver Kepp","orcid":"0000-0002-6081-9558","position":3,"is_corresponding":false},{"id":411018,"name":"Raphael H. Valdivia","orcid":"0000-0003-0961-073X","position":4,"is_corresponding":false},{"id":49720,"name":"Guido Kroemer","orcid":"0000-0002-9334-4405","position":5,"is_corresponding":false},{"id":411016,"name":"Barbara S. Sixt","orcid":"0000-0002-5607-8902","position":6,"is_corresponding":false},{"id":986065,"name":"Karsten Meier","orcid":null,"position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-19T00:31:26.161109Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}