[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-446112-105":59,"doc-detail-446112-en":131},{"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":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","beyond-the-matrix-rethinking-antibiotic-tolerance-in-cf-biofilms-using-3d-models","Beyond the matrix - rethinking antibiotic tolerance in CF biofilms using 3D models","","Chronic lung infections in cystic fibrosis are linked to Pseudomonas aeruginosa biofilms that show high antibiotic tolerance without a clear mechanism. This study uses 3D biofilm models based on acetylated alginate and DNA to test how the biofilm matrix affects antibiotic diffusion and efficacy. Antibiotic diffusion is largely unaffected by acetylation or DNA, yet bacterial tolerance increases strongly after encapsulation in alginate and is further enhanced by acetylation. DNA addition reduces tolerance in a drug-specific manner, while mucoid biofilms show strong penetration retardation but saturation within 20 hours.",{"@graph":69,"@context":123},[70,84,106],{"@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/beyond-the-matrix-rethinking-antibiotic-tolerance-in-cf-biofilms-using-3d-models/446112/",{"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/beyond-the-matrix-rethinking-antibiotic-tolerance-in-cf-biofilms-using-3d-models/446112.png","ImageObject",300,407,{"name":92,"@type":93},"Riley West","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-05","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What problem does the study address in cystic fibrosis biofilm infections?","Question",{"text":113,"@type":114},"It addresses chronic Pseudomonas aeruginosa biofilm infections in cystic fibrosis that exhibit high antibiotic tolerance without a well-defined explanation of the underlying mechanism.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How do the researchers model the biofilm matrix for antibiotic testing?",{"text":118,"@type":114},"They build 3D biofilm models using acetylated alginate and DNA, seeded with P. aeruginosa, to mimic mucoid biofilms and evaluate antibiotic diffusion and efficacy at scale.",{"name":120,"@type":111,"acceptedAnswer":121},"What do the results show about antibiotic diffusion and tolerance?",{"text":122,"@type":114},"Antibiotic diffusion is not significantly impeded by acetylation or DNA incorporation, but bacterial tolerance increases greatly after encapsulation in alginate, with additional enhancement by acetylation; DNA mitigates this effect in a drug-specific way.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},446112,1790794730,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":41,"preview_page_count":4},1099523885074,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","npj | biofilms and microbiomes Article  \nPublished in partnership with Nanyang Technological University  \n[https://doi.org/10.1038/s41522-025-00869-6](https://doi.org/10.1038/s41522-025-00869-6)  \nBeyond the matrix: rethinking antibiotic tolerance in CF biofilms using 3D models  \n Check for updates  \n\n| Goodness Ogechi Osondu-Chuka1 , Stephan Schandl2, Andrea Scheberl1, Olivier Guillaume2, Aleksandr Ovsianikov2 & Erik Reimhult1  |  |\n| --- | --- |\n| Chronic lung infections in cystic fibrosis (CF) patients are associated with Pseudomonas aeruginosa biofilms exhibiting high antibiotic tolerance with no clear explanation. We investigate the role of the biofilm matrix in this antibiotic tolerance using 3D biofilm models based on acetylated alginate and DNA, mimicking mucoid biofilms. Printed from these bioinks seeded with P. aeruginosa (PAO1), these models support robust microcolony formation as observed in vivo and enable high-throughput assessment of antibiotic diffusion and efficacy. Surprisingly, antibiotic diffusion is not significantly impeded by acetylation or DNA incorporation. Despite this, bacterial tolerance increases tremendously upon encapsulation in alginate. Acetylation further enhances tolerance, particularly totobramycin, ciprofloxacin, and colistin. The addition of DNA mitigates this effect in a drug-specific manner. While mucoid biofilms, in contrast to the biofilm models, show significant retardation of antibiotic penetration, they also get saturated with all tested antibiotics within 20 h. This demonstrates that direct interaction with alginate or DNA does not explain the slow diffusion of antibiotics in mucoid P. aeruginosa biofilms. Ourfindings challenge the view that diffusion limitation or antibiotics binding by biofilm exopolysaccharides dominate biofilm resilience and highlight the need to target matrixinduced bacterial adaptation in the development of antibiofilm therapies. |  |\n| Cystic fibrosis is a genetic disorder that predominantly affects the lungs, causing the production of thick, viscous mucus that impairs normal respiratory function and fosters an environment conducive to chronic bacterial infections1,2. In CF patients, Pseudomonas aeruginosa (PA) emerges as a predominant pathogen responsible for persistent pulmonary infections3–5. This microorganism forms biofilms, which serve as a defensive mechanism against both antimicrobial treatments and the host’s immune system6,7. The presence of biofilms, characterized by their dense extracellular matrix (ECM), facilitates the persistence of infections that become impossible to eradicate8. The chronic nature of PA infections in CF patients is further exacerbated by the emergence of mucoid bacteria variants, which overproduce alginate, a key exopolysaccharide (EPS) that enhances biofilm stability and antibiotic tolerance9, 10.\u003Cbr>The EPS plays a vital role in PA’s ability to withstand antimicrobial treatment, with alginate, Pel, and Psl acting as protective and structural components11–13. Notably, PA secrete acetylated alginate, a modification that has been suggested to contribute to antibiotic tolerance by altering the biofilm’s physicochemical properties compared to pristine alginate14–16. In addition, extracellular DNA (eDNA), which originates from bacterial and host cell lysis or active secretion, contributes to biofilm integrity and | interacts with exopolysaccharides such as Psl to enhance structural strength and antimicrobial tolerance17–20. The strong polyanions alginate and eDNA are thought to play an instrumental role in inhibiting the diffusion of predominantly cationic antibiotics, preventing them from efficiently reaching bacteria within the biofilm21–25, but the weakly anionic Pel and cationic Psl were also implicated in biofilm PA antibiotic tolerance26–28. While alginate and eDNA have long been regarded as physical barriers that hinder antibiotic diffusion25,29–32, the extent to which biofilm tolerance arises directly from these physicochemical impediments and their ","cbCaipHEzgvv6cC2","https://ap.wps.com/l/cbCaipHEzgvv6cC2","pdf",1686865,12,"English","# Background\n## Cystic fibrosis and Pseudomonas aeruginosa biofilms\n## Biofilm matrix components and proposed roles\n# 3D biofilm modeling approach\n## Acetylated alginate and DNA-based models\n## Microcolony formation and diffusion assessment\n# Key findings\n## Diffusion effects of acetylation and DNA\n## Tolerance changes after alginate encapsulation\n## Comparison with mucoid biofilms\n# Implications for therapy\n## Targeting matrix-induced bacterial adaptation","[{\"question\":\"What problem does the study address in cystic fibrosis biofilm infections?\",\"answer\":\"It addresses chronic Pseudomonas aeruginosa biofilm infections in cystic fibrosis that exhibit high antibiotic tolerance without a well-defined explanation of the underlying mechanism.\"},{\"question\":\"How do the researchers model the biofilm matrix for antibiotic testing?\",\"answer\":\"They build 3D biofilm models using acetylated alginate and DNA, seeded with P. aeruginosa, to mimic mucoid biofilms and evaluate antibiotic diffusion and efficacy at scale.\"},{\"question\":\"What do the results show about antibiotic diffusion and tolerance?\",\"answer\":\"Antibiotic diffusion is not significantly impeded by acetylation or DNA incorporation, but bacterial tolerance increases greatly after encapsulation in alginate, with additional enhancement by acetylation; DNA mitigates this effect in a drug-specific way.\"}]","Beyond the matrix - rethinking antibiotic tolerance in CF biofilms using 3D models | PDF",1790714124]