{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:37:31Z","timestamp":1785404251782,"version":"3.56.0"},"posted":{"date-parts":[[2024,5,24]]},"group-title":"Microbiology","reference-count":59,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T00:00:00Z","timestamp":1716508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["1R21AI180574"],"award-info":[{"award-number":["1R21AI180574"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1R35GM124798"],"award-info":[{"award-number":["1R35GM124798"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,7,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The obligate intracellular bacterium\n                  <jats:italic>Chlamydia<\/jats:italic>\n                  alternates between two functional forms during its developmental cycle: elementary body (EB) and reticulate body (RB). However, the molecular mechanisms governing the transitions between these forms are unknown. Here, we present evidence cyclic di-AMP (c-di-AMP) is a key factor in triggering the transition from RB to EB (i.e., secondary differentiation) in the chlamydial developmental cycle. By overexpressing or knocking down expression of c-di-AMP synthase genes, we made strains producing different levels of c-di-AMP, which we linked to changes in secondary differentiation status. Increases in c-di-AMP resulted in an earlier increase in transcription of EB-associated genes, and this was further manifested in earlier production of EBs. In contrast, when c-di-AMP levels were decreased, EB production was reduced. Based on these data, we conclude there is a threshold level of c-di-AMP needed to trigger secondary differentiation in\n                  <jats:italic>Chlamydia<\/jats:italic>\n                  . This study identifies a mechanism by which secondary differentiation is initiated in\n                  <jats:italic>Chlamydia<\/jats:italic>\n                  and reveals a critical role for the second messenger signaling molecule c-di-AMP in this process.\n                <\/jats:p>","DOI":"10.1101\/2024.05.24.595738","type":"posted-content","created":{"date-parts":[[2024,5,25]],"date-time":"2024-05-25T00:45:11Z","timestamp":1716597911000},"source":"Crossref","is-referenced-by-count":0,"title":["The second messenger signaling molecule cyclic di-AMP drives developmental cycle progression in\n                  <i>Chlamydia trachomatis<\/i>"],"prefix":"10.64898","author":[{"given":"Junghoon","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3721-6839","authenticated-orcid":false,"given":"Scot P.","family":"Ouellette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025071114404465000_2024.05.24.595738v5.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.femsre.2005.03.002"},{"key":"2025071114404465000_2024.05.24.595738v5.2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.173.12.3821-3830.1991"},{"key":"2025071114404465000_2024.05.24.595738v5.3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.9.3937"},{"key":"2025071114404465000_2024.05.24.595738v5.4","first-page":"87","article-title":"Why is Chlamydia sensitive to penicillin in the absence of peptidoglycan?","volume":"2","year":"1993","journal-title":"Infect Agents Dis"},{"key":"2025071114404465000_2024.05.24.595738v5.5","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.58.3.835-837.1990"},{"key":"2025071114404465000_2024.05.24.595738v5.6","doi-asserted-by":"publisher","DOI":"10.1128\/JB.151.1.420-428.1982"},{"key":"2025071114404465000_2024.05.24.595738v5.7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005822"},{"key":"2025071114404465000_2024.05.24.595738v5.8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005590"},{"key":"2025071114404465000_2024.05.24.595738v5.9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2012.08100.x"},{"key":"2025071114404465000_2024.05.24.595738v5.10","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00034-20"},{"key":"2025071114404465000_2024.05.24.595738v5.11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1331135100"},{"key":"2025071114404465000_2024.05.24.595738v5.12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2006.05465.x"},{"key":"2025071114404465000_2024.05.24.595738v5.13","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00018-13"},{"key":"2025071114404465000_2024.05.24.595738v5.14","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200651200"},{"key":"2025071114404465000_2024.05.24.595738v5.15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1514026112"},{"key":"2025071114404465000_2024.05.24.595738v5.16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1990.tb04097.x"},{"key":"2025071114404465000_2024.05.24.595738v5.17","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.641340"},{"key":"2025071114404465000_2024.05.24.595738v5.18","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.010046"},{"key":"2025071114404465000_2024.05.24.595738v5.19","doi-asserted-by":"crossref","unstructured":"Quintana IM , Gibhardt J , Turdiev A , Hammer E , Commichau FM , Lee VT , Magni C , Stulke J . 2019. 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