{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T14:09:50Z","timestamp":1791468590103,"version":"4.3.4"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,1,3]],"date-time":"2018-01-03T00:00:00Z","timestamp":1514937600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,1,3]],"date-time":"2018-01-03T00:00:00Z","timestamp":1514937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Chlamydia<\/jats:italic><jats:italic>trachomatis<\/jats:italic> is the most common cause of bacterial sexually transmitted infection. It produces an unusual intracellular infection in which a vegetative form, called the reticulate body (RB), replicates and then converts into an elementary body (EB), which is the infectious form. Here we use quantitative three-dimensional electron microscopy\u00a0(3D EM) to show that <jats:italic>C. trachomatis<\/jats:italic> RBs divide by binary fission and undergo a sixfold reduction in size as the population expands. Conversion only occurs after at least six rounds of replication, and correlates with smaller RB size. These results suggest that RBs only convert into EBs below a size threshold, reached by repeatedly dividing before doubling in size. A stochastic mathematical model shows how replication-dependent RB size reduction produces delayed and asynchronous conversion, which are hallmarks of the <jats:italic>Chlamydia<\/jats:italic>\u00a0developmental cycle. Our findings support a model in which RB size controls the timing of RB-to-EB conversion without the need for an external signal.<\/jats:p>","DOI":"10.1038\/s41467-017-02432-0","type":"journal-article","created":{"date-parts":[[2017,12,28]],"date-time":"2017-12-28T16:46:13Z","timestamp":1514479573000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":115,"title":["Replication-dependent size reduction precedes differentiation in Chlamydia trachomatis"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2219-4673","authenticated-orcid":false,"given":"Jennifer K.","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germ\u00e1n A.","family":"Enciso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4631-4139","authenticated-orcid":false,"given":"Daniela","family":"Boassa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher N.","family":"Chander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy H.","family":"Lou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean S.","family":"Pairawan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melody C.","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic Y. M.","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark H.","family":"Ellisman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1354-507X","authenticated-orcid":false,"given":"Christine","family":"S\u00fctterlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,1,3]]},"reference":[{"key":"2432_CR1","first-page":"1","volume":"64","author":"CDC.","year":"2017","unstructured":"CDC. Summary of notifiable diseases and conditions -- united states, 2015. MMWR 64, 1\u2013143 (2017).","journal-title":"MMWR"},{"key":"2432_CR2","doi-asserted-by":"publisher","first-page":"e0143304","DOI":"10.1371\/journal.pone.0143304","volume":"10","author":"L Newman","year":"2015","unstructured":"Newman, L. et al. Global estimates of the prevalence and incidence of four curable sexually transmitted infections in 2012 based on systematic review and global reporting. PLoS ONE 10, e0143304 (2015).","journal-title":"PLoS ONE"},{"key":"2432_CR3","doi-asserted-by":"crossref","unstructured":"Batteiger, B. E. & Tan, M. in Mandell, Douglas, and Bennett\u2019s: Principles and Practice of Infectious Diseases (eds Bennett, J. E., Dolin, R. & Mandell, G. L.) 2154\u20132170 (Elsevier Inc., 2014).","DOI":"10.1016\/B978-1-4557-4801-3.00182-X"},{"key":"2432_CR4","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1097\/ICU.0b013e32835438fc","volume":"23","author":"SJ Bhosai","year":"2012","unstructured":"Bhosai, S. J., Bailey, R. L., Gaynor, B. D. & Lietman, T. M. Trachoma: an update on prevention, diagnosis, and treatment. Curr. Opin. Ophthalmol. 23, 288\u2013295 (2012).","journal-title":"Curr. Opin. Ophthalmol."},{"key":"2432_CR5","doi-asserted-by":"crossref","unstructured":"Hammerschlag, M. R., Kohlhoff, S. A. & Gaydos, C. A. in Mandell, Douglas, and Bennett\u2019s: Principles and Practice of Infectious Diseases (eds Bennett, J. E., Dolin, R. & Mandell, G. L.) 2174\u20132182 (Elsevier Inc., 2014).","DOI":"10.1016\/B978-1-4557-4801-3.00184-3"},{"key":"2432_CR6","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1016\/j.femsre.2005.03.002","volume":"29","author":"YM Abdelrahman","year":"2005","unstructured":"Abdelrahman, Y. M. & Belland, R. J. The chlamydial developmental cycle. FEMS Microbiol. Rev. 29, 949\u2013959 (2005).","journal-title":"FEMS Microbiol. Rev."},{"key":"2432_CR7","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1128\/mr.55.1.143-190.1991","volume":"55","author":"JW Moulder","year":"1991","unstructured":"Moulder, J. W. Interaction of chlamydiae and host cells in vitro. Microbiol. Rev. 55, 143\u2013190 (1991).","journal-title":"Microbiol. Rev."},{"key":"2432_CR8","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1111\/1758-2229.12130","volume":"6","author":"IS Tan","year":"2014","unstructured":"Tan, I. S. & Ramamurthi, K. S. Spore formation in Bacillus subtilis. Environ. Microbiol Rep. 6, 212\u2013225 (2014).","journal-title":"Environ. Microbiol Rep."},{"key":"2432_CR9","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1046\/j.1365-2958.2000.02057.x","volume":"37","author":"EI Shaw","year":"2000","unstructured":"Shaw, E. I. et al. Three temporal classes of gene expression during the Chlamydia trachomatis developmental cycle. Mol. Microbiol. 37, 913\u2013925 (2000).","journal-title":"Mol. Microbiol."},{"key":"2432_CR10","doi-asserted-by":"publisher","first-page":"8478","DOI":"10.1073\/pnas.1331135100","volume":"100","author":"RJ Belland","year":"2003","unstructured":"Belland, R. J. et al. Genomic transcriptional profiling of the developmental cycle of Chlamydia trachomatis. Proc. Natl Acad. Sci. USA 100, 8478\u20138483 (2003).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2432_CR11","first-page":"73","volume":"Pt 2","author":"SB Leighton","year":"1981","unstructured":"Leighton, S. B. SEM images of block faces, cut by a miniature microtome within the SEM - a technical note. Scan Electron Microsc. Pt 2,\u00a073\u201376 (1981).","journal-title":"Scan Electron Microsc."},{"key":"2432_CR12","doi-asserted-by":"publisher","first-page":"e329","DOI":"10.1371\/journal.pbio.0020329","volume":"2","author":"W Denk","year":"2004","unstructured":"Denk, W. & Horstmann, H. Serial block-face scanning electron microscopy to reconstruct three-dimensional tissue nanostructure. PLoS Biol. 2, e329 (2004).","journal-title":"PLoS Biol."},{"key":"2432_CR13","doi-asserted-by":"publisher","first-page":"12954","DOI":"10.1523\/JNEUROSCI.1087-13.2013","volume":"33","author":"PS Holcomb","year":"2013","unstructured":"Holcomb, P. S. et al. Synaptic inputs compete during rapid formation of the calyx of Held: a new model system for neural development. J. Neurosci. 33, 12954\u201312969 (2013).","journal-title":"J. Neurosci."},{"key":"2432_CR14","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1523\/JNEUROSCI.1600-12.2013","volume":"33","author":"SA Wilke","year":"2013","unstructured":"Wilke, S. A. et al. Deconstructing complexity: serial block-face electron microscopic analysis of the hippocampal mossy fiber synapse. J. Neurosci. 33, 507\u2013522 (2013).","journal-title":"J. Neurosci."},{"key":"2432_CR15","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/nmeth.2476","volume":"10","author":"M Helmstaedter","year":"2013","unstructured":"Helmstaedter, M. Cellular-resolution connectomics: challenges of dense neural circuit reconstruction. Nat. Methods 10, 501\u2013507 (2013).","journal-title":"Nat. Methods"},{"key":"2432_CR16","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/nmeth.3361","volume":"12","author":"S Mikula","year":"2015","unstructured":"Mikula, S. & Denk, W. High-resolution whole-brain staining for electron microscopic circuit reconstruction. Nat. Methods 12, 541\u2013546 (2015).","journal-title":"Nat. Methods"},{"key":"2432_CR17","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1038\/nchembio.2076","volume":"12","author":"JT Ngo","year":"2016","unstructured":"Ngo, J. T. et al. Click-EM for imaging metabolically tagged nonprotein biomolecules. Nat. Chem. Biol. 12, 459\u2013465 (2016).","journal-title":"Nat. Chem. Biol."},{"key":"2432_CR18","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.cell.2012.08.035","volume":"151","author":"HD Ou","year":"2012","unstructured":"Ou, H. D. et al. A structural basis for the assembly and functions of a viral polymer that inactivates multiple tumor suppressors. Cell 151, 304\u2013319 (2012).","journal-title":"Cell"},{"key":"2432_CR19","doi-asserted-by":"publisher","first-page":"2424","DOI":"10.1091\/mbc.E10-12-0950","volume":"23","author":"M Puhka","year":"2012","unstructured":"Puhka, M., Joensuu, M., Vihinen, H., Belevich, I. & Jokitalo, E. Progressive sheet-to-tubule transformation is a general mechanism for endoplasmic reticulum partitioning in dividing mammalian cells. Mol. Biol. Cell 23, 2424\u20132432 (2012).","journal-title":"Mol. Biol. Cell"},{"key":"2432_CR20","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1128\/jb.124.2.857-862.1975","volume":"124","author":"TE Shehata","year":"1975","unstructured":"Shehata, T. E. & Marr, A. G. Effect of temperature on the size of Escherichia coli cells. J. Bacteriol. 124, 857\u2013862 (1975).","journal-title":"J. Bacteriol."},{"key":"2432_CR21","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.cub.2014.12.009","volume":"25","author":"S Taheri-Araghi","year":"2015","unstructured":"Taheri-Araghi, S. et al. Cell-size control and homeostasis in bacteria. Curr. Biol. 25, 385\u2013391 (2015).","journal-title":"Curr. Biol."},{"key":"2432_CR22","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1016\/j.cell.2014.11.022","volume":"159","author":"M Campos","year":"2014","unstructured":"Campos, M. et al. A constant size extension drives bacterial cell size homeostasis. Cell 159, 1433\u20131446 (2014).","journal-title":"Cell"},{"key":"2432_CR23","doi-asserted-by":"publisher","first-page":"6791","DOI":"10.1128\/jb.177.23.6791-6797.1995","volume":"177","author":"T Akerlund","year":"1995","unstructured":"Akerlund, T., Nordstrom, K. & Bernander, R. Analysis of cell size and DNA content in exponentially growing and stationary-phase batch cultures of Escherichia coli. J. Bacteriol. 177, 6791\u20136797 (1995).","journal-title":"J. Bacteriol."},{"key":"2432_CR24","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1099\/00221287-19-3-607","volume":"19","author":"NO Kjeldgaard","year":"1958","unstructured":"Kjeldgaard, N. O., Maaloe, O. & Schaechter, M. The transition between different physiological states during balanced growth of Salmonella typhimurium. J. Gen. Microbiol. 19, 607\u2013616 (1958).","journal-title":"J. Gen. Microbiol."},{"key":"2432_CR25","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1242\/jcs.24.1.51","volume":"24","author":"PA Fantes","year":"1977","unstructured":"Fantes, P. A. Control of cell size and cycle time in Schizosaccharomyces pombe. J. Cell Sci. 24, 51\u201367 (1977).","journal-title":"J. Cell Sci."},{"key":"2432_CR26","doi-asserted-by":"publisher","first-page":"e1005822","DOI":"10.1371\/journal.ppat.1005822","volume":"12","author":"Y Abdelrahman","year":"2016","unstructured":"Abdelrahman, Y., Ouellette, S. P., Belland, R. J. & Cox, J. V. Polarized cell division of Chlamydia trachomatis. PLoS Pathog. 12, e1005822 (2016).","journal-title":"PLoS Pathog."},{"key":"2432_CR27","doi-asserted-by":"crossref","first-page":"2388","DOI":"10.1128\/jb.91.6.2388-2389.1966","volume":"91","author":"AG Marr","year":"1966","unstructured":"Marr, A. G., Harvey, R. J. & Trentini, W. C. Growth and division of Escherichia coli. J. Bacteriol. 91, 2388\u20132389 (1966).","journal-title":"J. Bacteriol."},{"key":"2432_CR28","unstructured":"Motulsky, H. Intuitive Biostatistics: A Nonmathematical Guide to Statistical Thinking. (Oxford University Press, 2014)."},{"key":"2432_CR29","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1007\/s11538-005-9024-1","volume":"68","author":"DP Wilson","year":"2006","unstructured":"Wilson, D. P., Timms, P., McElwain, D. L. & Bavoil, P. M. Type III secretion, contact-dependent model for the intracellular development of Chlamydia. Bull. Math. Biol. 68, 161\u2013178 (2006).","journal-title":"Bull. Math. Biol."},{"key":"2432_CR30","doi-asserted-by":"publisher","first-page":"a019083","DOI":"10.1101\/cshperspect.a019083","volume":"8","author":"AA Amodeo","year":"2016","unstructured":"Amodeo, A. A. & Skotheim, J. M. Cell-SizeControl. Cold Spring Harb. Perspect. Biol. 8, a019083 (2016).","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"2432_CR31","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1128\/aem.62.2.328-331.1996","volume":"62","author":"J Ossewaarde","year":"1996","unstructured":"Ossewaarde, J., de Vries, A., Bestebroer, T. & Angulo, A. Application of a Mycoplasma group-specific PCR for monitoring decontamination of Mycoplasma-infected Chlamydia sp. strains. Appl. Environ. Microbiol. 62, 328\u2013331 (1996).","journal-title":"Appl. Environ. Microbiol."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-017-02432-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-017-02432-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-017-02432-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T01:19:30Z","timestamp":1671758370000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-017-02432-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,3]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["2432"],"URL":"https:\/\/doi.org\/10.1038\/s41467-017-02432-0","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,3]]},"assertion":[{"value":"8 June 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 January 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"45"}}