{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T22:48:20Z","timestamp":1783464500936,"version":"3.55.0"},"posted":{"date-parts":[[2026,2,11]]},"group-title":"Microbiology","reference-count":26,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"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":["140167"],"award-info":[{"award-number":["140167"]}],"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":["154305"],"award-info":[{"award-number":["154305"]}],"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"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  The unique chlamydial developmental cycle comprises three stages: primary differentiation of infectious elementary bodies (EBs) into reticulate bodies (RBs), RB replication, and secondary differentiation into progeny EBs. Extensive chromosome remodeling during RB-to-EB differentiation is thought to be mediated by the histones HctA and HctB. Here, we used an inducible CRISPR interference system to repress\n                  <jats:italic>hctA, hctB<\/jats:italic>\n                  , or both genes during development in\n                  <jats:italic>Chlamydia trachomatis<\/jats:italic>\n                  . Surprisingly, repression of either histone gene alone or in combination caused only modest reductions in EB yield and did not prevent nucleoid condensation during the parental developmental cycle. In contrast, when progeny EBs generated under histone-repressing conditions were used to initiate secondary infections in the absence of inducer, histone deficiency during EB maturation profoundly impaired fitness in the next infection cycle. Secondary cultures initiated with HctA-deficient EBs exhibited a delayed onset of genome replication, consistent with inefficient primary EB-to-RB differentiation, whereas combined repression of\n                  <jats:italic>hctA<\/jats:italic>\n                  and\n                  <jats:italic>hctB<\/jats:italic>\n                  caused both delayed genome replication and persistently reduced genome accumulation, indicative of defects in RB formation and subsequent growth. Repression of\n                  <jats:italic>hctB<\/jats:italic>\n                  alone did not measurably affect genome replication in secondary cultures. Together, these findings reveal a transgenerational role for chlamydial histones and establish chromosome organization during EB maturation as a key determinant of developmental fitness across infection cycles.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>IMPORTANCE<\/jats:title>\n                  <jats:p>Chlamydial histones HctA and HctB are unusual among bacterial chromatin-binding proteins in that they share sequence homology with mammalian histones and are developmentally regulated during the formation of infectious particles. Here, we show that reduced expression of HctA and HctB has only modest effects on genome condensation and EB production, consistent with partial functional redundancy between the two histones and suggesting that additional chromatin factors contribute to EB chromosome compaction. In contrast, deficiency of HctA and HctB during EB maturation has profound consequences in the next infection cycle, impairing primary EB-to-RB differentiation and subsequent RB growth. These findings reveal a previously unrecognized transgenerational role for chlamydial histones and establish chromosome organization during EB maturation as a key determinant of developmental fitness across infection cycles.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.02.10.705219","type":"posted-content","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T06:00:25Z","timestamp":1770876025000},"source":"Crossref","is-referenced-by-count":1,"title":["Chlamydial Histones Control Developmental Fitness in the Next Infection Cycle"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0771-1078","authenticated-orcid":false,"given":"Yuxuan","family":"Wang","sequence":"first","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\/0000-0002-1043-3681","authenticated-orcid":false,"given":"Matthew","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Temitope V.","family":"Coker","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA"},{"name":"Jiangsu Agri-animal Husbandry Vocational College, Taizhou City, China 225300"}],"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\/0000-0001-7053-5009","authenticated-orcid":false,"given":"Guangming","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Health San Antonio, San Antonio, TX 78229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4903-926X","authenticated-orcid":false,"given":"Huizhou","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"1","key":"2026021403051227000_2026.02.10.705219v1.1","doi-asserted-by":"crossref","first-page":"2503423","DOI":"10.1080\/21505594.2025.2503423","article-title":"Pathogenicity and virulence of Chlamydia trachomatis: Insights into host interactions, immune evasion, and intracellular survival","volume":"16","year":"2025","journal-title":"Virulence"},{"key":"2026021403051227000_2026.02.10.705219v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2016.30"},{"issue":"1","key":"2026021403051227000_2026.02.10.705219v1.3","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41467-017-02432-0","article-title":"Replication-dependent size reduction precedes differentiation in Chlamydia trachomatis","volume":"9","year":"2018","journal-title":"Nature communications"},{"key":"2026021403051227000_2026.02.10.705219v1.4","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00106-07"},{"key":"2026021403051227000_2026.02.10.705219v1.5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0703218104"},{"key":"2026021403051227000_2026.02.10.705219v1.6","doi-asserted-by":"crossref","unstructured":"Ouellette SP , Lee J , Cox JV : Division without Binary Fission: Cell Division in the FtsZ-Less Chlamydia. 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