{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:07:54Z","timestamp":1789103274957,"version":"build-2803163510"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013280","name":"Major Basic Research Project of the Natural Science Foundation of the Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","award":["the Major Program of Natural Science Foundation of Jiangsu Higher Education Institutions"],"award-info":[{"award-number":["the Major Program of Natural Science Foundation of Jiangsu Higher Education Institutions"]}],"id":[{"id":"10.13039\/501100013280","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013280","name":"Major Basic Research Project of the Natural Science Foundation of the Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","award":["the Sixth Jianghai Elite Training Project of Nantong City"],"award-info":[{"award-number":["the Sixth Jianghai Elite Training Project of Nantong City"]}],"id":[{"id":"10.13039\/501100013280","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    <jats:italic>Chlamydia<\/jats:italic>\n                    is an obligate intracellular bacterial pathogen responsible for sexually transmitted infections and blindness worldwide. In our search for antichlamydial agents from natural sources, we identified pyocyanin, a phenazine derivative from\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    . Previous studies showed that pyocyanin disables elementary body (EB) infectivity at low concentrations and inhibits intracellular growth at higher concentrations. In the present study, we show that its antichlamydial activity is primarily attributed to the intracellular developmental stage. Complete inhibition of detectable infectious progeny was achieved at 16\u00a0\u03bcM\u00a0at the standard 36 hpi endpoint, while its effect on the infection stage reached only approximately 60% inhibition. Two independent delayed treatment assays revealed that pyocyanin reduces the infectivity of newly formed EBs without reducing their number. Furthermore, pyocyanin delays rather than arrests the chlamydial developmental cycle, and its inhibitory effect is reversible, requiring sustained drug exposure for optimal efficacy. These findings position pyocyanin among a growing class of antichlamydial agents that target distinct steps of the pathogen\u2019s developmental cycle and support its potential as a chemical probe for chlamydial biology and a lead compound for drug development.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1921161","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T04:34:38Z","timestamp":1789101278000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pyocyanin reversibly inhibits Chlamydia by impairing newly formed elementary body infectivity and delaying the developmental cycle"],"prefix":"10.3389","volume":"17","author":[{"given":"Xinyang","family":"Sun","sequence":"first","affiliation":[{"name":"School of Pharmacy, Nantong University","place":["Nantong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Sang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nantong University","place":["Nantong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunxin","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nantong University","place":["Nantong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leyi","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nantong University","place":["Nantong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nantong University","place":["Nantong, China"]},{"name":"Jiangsu Key Laboratory of Inflammation and Molecular Targets, Nantong University","place":["Nantong, China"]},{"name":"Nantong Key Laboratory of Small Molecular Drug Innovation, Nantong University","place":["Nantong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Bao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nantong University","place":["Nantong, China"]},{"name":"Jiangsu Key Laboratory of Inflammation and Molecular Targets, Nantong University","place":["Nantong, China"]},{"name":"Nantong Key Laboratory of Small Molecular Drug Innovation, Nantong University","place":["Nantong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1016\/j.femsre.2005.03.002","article-title":"The chlamydial developmental cycle","volume":"29","author":"AbdelRahman","year":"2005","journal-title":"FEMS Microbiol. Rev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.febslet.2007.01.013","article-title":"Small molecule inhibitors of type III secretion in yersinia block the Chlamydia pneumoniae infection cycle","volume":"581","author":"Bailie","year":"2007","journal-title":"FEBS Lett."},{"key":"B3","doi-asserted-by":"publisher","first-page":"302","DOI":"10.3389\/fnagi.2018.00302","article-title":"Chlamydia Pneumoniae: an etiologic agent for late-onset dementia","volume":"10","author":"Balin","year":"2018","journal-title":"Front. Aging Neurosci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"413","DOI":"10.2174\/1573406415666190708145639","article-title":"Synthesis and assessment of 3-substituted phenazines as novel antichlamydial agents","volume":"16","author":"Bao","year":"2020","journal-title":"Med. Chem."},{"key":"B5","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1080\/10286020.2021.1982909","article-title":"Synthesis of 1-substituted phenazines as novel antichlamydial agents","volume":"24","author":"Bao","year":"2022","journal-title":"J. Asian Nat. Prod. Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1159\/000314998","article-title":"Decreased susceptibility to azithromycin and doxycycline in clinical isolates of Chlamydia trachomatis obtained from recurrently infected female patients in India","volume":"56","author":"Bhengraj","year":"2010","journal-title":"Chemotherapy"},{"key":"B7","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1099\/0022-1317-51-8-623","article-title":"Chlamydia pneumoniae pathogenesis","volume":"51","author":"Campbell","year":"2002","journal-title":"J. Med. Microbiol."},{"key":"B8","volume-title":"Sexually Transmitted Disease Surveillance 2022","year":"2024"},{"key":"B9","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1095\/biolreprod.107.067819","article-title":"Male genital tract chlamydial infection: implications for pathology and infertility","volume":"79","author":"Cunningham","year":"2008","journal-title":"Biol. Reprod."},{"key":"B10","doi-asserted-by":"publisher","first-page":"4554","DOI":"10.1073\/pnas.1000087107","article-title":"Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation","volume":"108","author":"Dethlefsen","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B11","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1038\/nrmicro.2016.30","article-title":"Chlamydia cell biology and pathogenesis","volume":"14","author":"Elwell","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1007\/s11904-025-00720-3","article-title":"Antimicrobial resistance in curable sexually transmitted infections","volume":"22","author":"Giacani","year":"2025","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e1004849","DOI":"10.1371\/journal.pmed.1004849","article-title":"Vaccines to prevent bacterial sexually transmitted infections: promise, progress, and public health potential","volume":"22","author":"Gottlieb","year":"2025","journal-title":"PLoS Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"S134","DOI":"10.1086\/652395","article-title":"Risk of sequelae after Chlamydia trachomatis genital infection in women","volume":"201","author":"Haggerty","year":"2010","journal-title":"J. Infect. Dis."},{"key":"B15","doi-asserted-by":"publisher","first-page":"43","DOI":"10.3390\/microorganisms4040043","article-title":"Lead discovery strategies for identification of Chlamydia pneumoniae inhibitors","volume":"4","author":"Hanski","year":"2016","journal-title":"Microorganisms"},{"key":"B16","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/nature07578","article-title":"Chlamydia causes fragmentation of the golgi compartment to ensure replication","volume":"457","author":"Heuer","year":"2009","journal-title":"Nature"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1843","DOI":"10.1128\/IAI.72.4.1843-1855.2004","article-title":"Chlamydial persistence: beyond the biphasic paradigm","volume":"72","author":"Hogan","year":"2004","journal-title":"Infect. Immun."},{"key":"B18","doi-asserted-by":"publisher","first-page":"7653","DOI":"10.2147\/DDDT.S545216","article-title":"Natural products from traditional Chinese medicine: potential therapeutic agents in cancer therapy-induced cardiotoxicity","volume":"19","author":"Jin","year":"2025","journal-title":"Drug Des. Dev. Ther."},{"key":"B19","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1186\/s12879-015-1030-9","article-title":"Treatment challenges for urogenital and anorectal Chlamydia trachomatis","volume":"15","author":"Kong","year":"2015","journal-title":"BMC Infect. Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1055\/s-0043-100382","article-title":"Antichlamydial dimeric indole derivatives from marine actinomycete Rubrobacter radiotolerans","volume":"83","author":"Li","year":"2017","journal-title":"Planta Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e02260","DOI":"10.1128\/AAC.02260-17","article-title":"Pyocyanin inhibits chlamydia infection by disabling infectivity of the elementary body and disrupting intracellular growth","volume":"62","author":"Li","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1970","DOI":"10.1039\/d2np00027j","article-title":"Recent ring distortion reactions for diversifying complex natural products","volume":"39","author":"Li","year":"2022","journal-title":"Nat. Product. Rep."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1783916","DOI":"10.3389\/fmicb.2026.1783916","article-title":"Kaempferol inhibits Chlamydia psittaci proliferation by blocking lipid transport and RB-EB differentiation","volume":"17","author":"Lin","year":"2026","journal-title":"Front. Microbiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"116708","DOI":"10.1016\/j.biopha.2024.116708","article-title":"Natural products as glycolytic inhibitors for cervical cancer treatment: a comprehensive review","volume":"175","author":"Liu","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"B25","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1007\/s11274-024-03889-0","article-title":"A biomedical perspective of pyocyanin from pseudomonas aeruginosa: its applications and challenges","volume":"40","author":"Mudaliar","year":"2024","journal-title":"World J. Microbiol. Biotechnol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e00772920","DOI":"10.1128\/IAI.00729-20","article-title":"The small molecule H89 inhibits chlamydia inclusion growth and production of infectious progeny","volume":"89","author":"Mu\u00f1oz","year":"2021","journal-title":"Infect. Immun."},{"key":"B27","doi-asserted-by":"publisher","first-page":"14566","DOI":"10.1073\/pnas.0606412103","article-title":"A small-molecule inhibitor of type III secretion inhibits different stages of the infectious cycle of Chlamydia trachomatis","volume":"103","author":"Muschiol","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B28","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural products as sources of new drugs over the nearly four decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. Nat. Prod."},{"key":"B29","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.tim.2026.02.003","article-title":"Koalas first: lessons from a wildlife chlamydia vaccine","volume":"34","author":"Pollak","year":"2026","journal-title":"Trends Microbiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"548","DOI":"10.2471\/BLT.18.228486","article-title":"Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016","volume":"97","author":"Rowley","year":"2019","journal-title":"Bull. World Health Organ."},{"key":"B31","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1038\/s41572-022-00359-5","article-title":"Trachoma","volume":"8","author":"Solomon","year":"2022","journal-title":"Nat. Rev. Dis. Prim."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1086\/315372","article-title":"Multiple drug-resistant Chlamydia trachomatis associated with clinical treatment failure","volume":"181","author":"Somani","year":"2000","journal-title":"J. Infect. Dis."},{"key":"B33","doi-asserted-by":"publisher","first-page":"109123","DOI":"10.1016\/j.intimp.2022.109123","article-title":"Salidroside alleviates severe acute pancreatitis-triggered pancreatic injury and inflammation by regulating miR-217-5p\/YAF2 axis","volume":"111","author":"Wang","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"4322","DOI":"10.3390\/app15084322","article-title":"Antimicrobial susceptibility testing in chlamydia trachomatis: the current state of evidence and a call for more national surveillance studies","volume":"15","author":"Wang","year":"2025","journal-title":"Pathogens"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15585\/mmwr.rr7004a1","article-title":"Sexually transmitted infections treatment guidelines, 2021","volume":"70","author":"Workowski","year":"2021","journal-title":"MMWR Recomm. Rep."},{"key":"B36","doi-asserted-by":"publisher","first-page":"S88","DOI":"10.1086\/652394","article-title":"Chlamydia trachomatis persistence in vitro: an overview","volume":"201","author":"Wyrick","year":"2010","journal-title":"J. Infect. Dis."},{"key":"B37","doi-asserted-by":"publisher","first-page":"610","DOI":"10.3390\/md19110610","article-title":"Advances in phenazines over the past decade: review of their pharmacological activities, mechanisms of action, biosynthetic pathways and synthetic strategies","volume":"19","author":"Yan","year":"2021","journal-title":"Mar. Drugs"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1921161\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T04:34:46Z","timestamp":1789101286000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1921161\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":37,"alternative-id":["10.3389\/fphar.2026.1921161"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1921161","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]},"article-number":"1921161"}}