[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-445856-105":59,"doc-detail-445856-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","zoonotic-streptococcus-imports-glucose-to-inhibit-stringent-response-and-promote-growth-during-meningitis","Zoonotic Streptococcus imports glucose to inhibit stringent response and promote growth during meningitis","","Zoonotic Streptococcus equi subsp. zooepidemicus proliferates in the meninges and drives severe disease in animals and humans, yet the mechanisms enabling hypervirulence in cerebrospinal fluid (CSF) are unclear. Using genetically barcoded strains, researchers show that only a small number of clones invade, then replicate extensively in CSF. Transposon insertion sequencing and validation with mannosephosphotransferase system (PTSman)–defective mutants identify PTSman as essential for growth. A species-specific PTSman promoter supports constitutive glucose acquisition under low-glucose conditions while limiting stringent response activation, enabling CSF adaptation.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/zoonotic-streptococcus-imports-glucose-to-inhibit-stringent-response-and-promote-growth-during-meningitis/445856/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/zoonotic-streptococcus-imports-glucose-to-inhibit-stringent-response-and-promote-growth-during-meningitis/445856.png","ImageObject",300,407,{"name":92,"@type":93},"Ophelia","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-04","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What question does the study address about S. zooepidemicus in meningitis?","Question",{"text":112,"@type":113},"It investigates the mechanisms that allow hypervirulent S. zooepidemicus to invade the meninges and proliferate within cerebrospinal fluid (CSF).","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How many S. zooepidemicus clones invade the meninges after systemic infection in mice?",{"text":117,"@type":113},"Following infection, only about 1–10 S. zooepidemicus clones invade the meninges, where they subsequently replicate extensively in CSF.",{"name":119,"@type":110,"acceptedAnswer":120},"What role does PTSman play in CSF growth and stress regulation?",{"text":121,"@type":113},"PTSman, which imports glucose, is essential for proliferation in CSF. Its promoter rewiring enables glucose acquisition at low glucose concentrations while preventing activation of the stringent response, supporting bacterial replication.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},445856,1790790615,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},7971461741311,"https://ap-avatar.wpscdn.com/avatar/74000253aff267980c6?x-image-process=image/resize,m_fixed,w_180,h_180&k=1779345379180704826","nature microbiology  \nArticle [https://doi.org/10.1038/s41564-025-02194-2](https://doi.org/10.1038/s41564-025-02194-2)  \nZoonotic Streptococcus imports glucose to inhibit stringent response and promote growth during meningitis  \n\n| Received: 9 July 2024 Chen Yuan1, Karthik Hullahalli2,3, Hao Huang1, Siqi Zhao1, Wenqing Wang1,\u003Cbr>Accepted: 17 October 2025  Xingyu Tian1, Xin Li  1, Linya Xia1, Yuchang Wang1, Fei Pan1, Ying Liang1,    Yurui Xie1, Yue Li1, Hongjie Fan  1,4, Matthew K. Waldor  2 & Zhe Ma  1,4  Published online: 15 December 2025 |  |  |\n| --- | --- | --- |\n| | Proliferation of the emerging zoonotic pathogen Streptococcus equi subsp. zooepidemicus in the meninges is linked to mortality in pigs and morbidity in humans. The mechanisms underlying the remarkable capacity of hypervirulent S. zooepidemicus to proliferate in cerebrospinal fluid (CSF) are largely undefined. Here, using genetically barcodedS. zooepidemicus, we found that following systemic infection of mice, only~1–10 S. zooepidemicus clones invade the meninges where they subsequently replicate~107-fold. Subsequent transposon insertion sequencing experiments, plus validation work with bacterial mannosephosphotransferase system (PTSman)-defective strains, identified the PTSman, which imports glucose, as essential for\u003Cbr>S. zooepidemicus proliferation inCSF. TheS. zooepidemicus PTSman promoter confers species-specific constitutive transcription of PTSman, enabling glucose acquisition at low glucose concentrationsand limiting activation of the stringent response, leading to pathogen replication inCSF. Our findings reveal how therewiring of PTSman in the control ofS. zooepidemicus metabolism enables this pathogen to adapt to and replicate inCSF during meningitis. |  |\n| Bacterial meningitis occurs when bacteria invade the subarachnoid space, which contains cerebrospinal fluid (CSF) and blood vessels. Proliferation of bacteria in the CSFand the ensuing inflammation can also damage the brain parenchyma1. Bacterial meningitis results in high mortality and morbidity that often includes severe neurological sequelae2,3. Several Streptococcus species cause bacterial meningitis, with Streptococcus pneumoniae being predominant in adult community-acquired meningitis1 and Streptococcus agalactiae (group B Streptococcus (GBS)) responsible for ~35% of early-onset neonatal meningitis4. Recently, the swine industry in North America and Europe has experienced an emerging pandemic of meningitis caused by Streptococcusequi subsp. zooepidemicus5,6, with infected pigs showing high S. zooepidemicus colony-forming units (CFU; >108 ml−1) within the CSF7. |  | Notably, this pathogen has also been implicated in numerous human lethal meningitis cases globally8,9. Between 2021 and 2022, Italy experienced anS. zooepidemicus outbreak with 37 clinical cases, of which 5 patients died from meningitis10.\u003Cbr>To invade the central nervous system (CNS) from blood, pathogens must first penetrate the blood–CSF/brain barrier11,12. Although penetration of these barriers is challenging, pathogens may benefit from entering this immune-privileged niche. Contemporary studies into bacterial CNS invasion have primarily focused on elucidating strategies used by bacteria to penetrate the blood–CSF/brain barrier. For example, S. zooepidemicus strains in the ST194 clade encode factors such asS. zooepidemicus M protein (SzM) and BifA that facilitate the pathogen’straversal ofthe blood–brain barrier (BBB)13,14. By |\n\n1Ministry of Agriculture Key Laboratory of Animal Bacteriology, the International Joint Laboratory of Animal Health and Food Safety, and College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China. 2Howard Hughes Medical Institute, Brigham and Women’s Hospital Division of Infectious Diseases, and Department of Microbiology, Harvard Medical School, Boston, MA, USA. 3Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA. 4J","cbCaitLUZ6XRZy5K","https://ap.wps.com/l/cbCaitLUZ6XRZy5K","pdf",20234120,33,"English","# Introduction\n## Zoonotic meningitis burden and knowledge gaps\n## CNS invasion and nutrient/stress constraints\n# Results\n## Few clones invade meninges and replicate in CSF\n## PTSman is essential for CSF proliferation\n## Low-glucose promoter rewiring limits stringent response\n# Conclusion","[{\"question\":\"What question does the study address about S. zooepidemicus in meningitis?\",\"answer\":\"It investigates the mechanisms that allow hypervirulent S. zooepidemicus to invade the meninges and proliferate within cerebrospinal fluid (CSF).\"},{\"question\":\"How many S. zooepidemicus clones invade the meninges after systemic infection in mice?\",\"answer\":\"Following infection, only about 1–10 S. zooepidemicus clones invade the meninges, where they subsequently replicate extensively in CSF.\"},{\"question\":\"What role does PTSman play in CSF growth and stress regulation?\",\"answer\":\"PTSman, which imports glucose, is essential for proliferation in CSF. Its promoter rewiring enables glucose acquisition at low glucose concentrations while preventing activation of the stringent response, supporting bacterial replication.\"}]","Zoonotic Streptococcus imports glucose to inhibit stringent response and promote growth during meningitis | PDF",1790713016,83]