{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T23:11:17Z","timestamp":1790118677999,"version":"4.0.1"},"posted":{"date-parts":[[2025,5,30]]},"group-title":"Microbiology","reference-count":54,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AI140167"],"award-info":[{"award-number":["AI140167"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AI154305"],"award-info":[{"award-number":["AI154305"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AI182210"],"award-info":[{"award-number":["AI182210"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"crossref","award":["201806370171"],"award-info":[{"award-number":["201806370171"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Bacterial stress responses rely on transcriptional regulation by sigma factors and repressors. In\n                  <jats:italic>Chlamydia<\/jats:italic>\n                  , which lacks a dedicated heat shock sigma factor, repressor HrcA limits chaperone gene expression under non-stressed conditions. While HrcA function may be enhanced by the chaperone GroESL in a positive feedback loop, here we identify a heat-induced negative feedback loop mediated by HagF, a protein unique to Chlamydiota and conserved across\n                  <jats:italic>Chlamydia<\/jats:italic>\n                  species. We show that HrcA represses\n                  <jats:italic>hagF<\/jats:italic>\n                  , but heat shock induces\n                  <jats:italic>hagF<\/jats:italic>\n                  expression, leading to HagF accumulation and binding to HrcA. Structural modeling and pulldown assays indicate that HagF blocks HrcA dimerization, impairing DNA binding. This relieves repression of the\n                  <jats:italic>hrcA-grpE-dnaK<\/jats:italic>\n                  operon and promotes secondary differentiation in the developmental cycle, enabling infectious elementary bodies to form under heat stress. Our findings reveal dual feedback regulation that tunes chaperone gene expression and illustrate how transcriptional repression can be modulated in a minimal-genome pathogen.\n                <\/jats:p>","DOI":"10.1101\/2025.05.30.657042","type":"posted-content","created":{"date-parts":[[2025,5,31]],"date-time":"2025-05-31T00:05:20Z","timestamp":1748649920000},"source":"Crossref","is-referenced-by-count":7,"title":["A lineage-specific heat-induced feedback loop controls HrcA to promote chlamydial fitness under stress"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8186-1088","authenticated-orcid":false,"given":"Yehong","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China"},{"name":"Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA"},{"name":"Department of Parasitology, Central South University 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University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7046-9854","authenticated-orcid":false,"given":"Joseph D.","family":"Fondell","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9013-742X","authenticated-orcid":false,"given":"Xiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Central South University Xiangya Medical School, Changsha, Hunan 410078, 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