Biofilm最新文献

{"title":"A novel MIR imaging approach for precise detection of S. epidermidis biofilms in seconds","authors":"Björn van Marwick ,&nbsp;Tatyana N. Sevastyanova ,&nbsp;Felix Wühler ,&nbsp;Barbara Schneider-Wald ,&nbsp;Cornelia Loy ,&nbsp;Sascha Gravius ,&nbsp;Matthias Rädle ,&nbsp;Andreas Schilder","doi":"10.1016/j.bioflm.2025.100270","DOIUrl":"10.1016/j.bioflm.2025.100270","url":null,"abstract":"<div><div>The impact of microbial biofilm growth poses a threat to both human health and the performance of industrial systems, manifesting as a global crisis with noteworthy economic implications for modern society. Exploring new methods and alternative approaches for the detection of biofilm signatures are imperative for developing optimized and cost-effective strategies that can help to identify early-stage biofilm formation. Clinical diagnostic technologies are constantly looking for more affordable, practical and faster methods of prevention and detection of chronic infections in periprosthetic joint infections (PJIs), which are often characterized by biofilm formation on implant surfaces. <em>Staphylococcus epidermidis (SE)</em> is especially known for its strong biofilm production and is considered a leading cause of biomaterial-associated infections, including PJIs. Implant-associated infections are severe and difficult to treat, therefore it is crucial to continue identifying bacterial biomarkers that contribute to its structural stability and attachment to implant surfaces. This study presents a pioneering approach for fast spectral detection of biofilm formation with a novel mid-infrared (MIR) scanning system. To highlight the advantages of our MIR system, we performed a comparative analysis with measurements from a commercially available Fourier-transform infrared (FTIR) scanner. We have assessed SE biofilms grown for 3 days comparing the processing times between a commercially available infrared (IR) scanning system (∼8 h/cm²), and our innovative scanning approach with rapid self-built MIR detection, achieving a reduction in scanning time to seconds. K-means clustering analysis identified pronounced differences in distribution of clusters, representing a significant variation between biofilm producing (RP62A) and non-biofilm producing (ATCC 12228) bacterial strains. The distribution serves as a critical tool for identifying biofilm phenotypes, particularly where poly-N-acetylglucosamine (PNAG), a key constituent of extracellular polymeric substances (EPS) in <em>S. epidermidis</em>, represents the dominant mass fraction in the samples analyzed by our infrared (IR) scanning systems. In addition to faster processing times, our novel MIR system demonstrated significantly higher sensitivity compared to FTIR, enabling clear differentiation between the chemical signatures of biofilm and planktonic strains. The corresponding novel approach integrates advanced data analytics with a newly designed rapid MIR prototype, enabling optimized and swift detection of biofilm signatures. These signatures, now recognized as critical targets in diagnosing complex infections, provide an alternative to traditional microbial detection methods in clinical diagnostics.</div></div>","PeriodicalId":55844,"journal":{"name":"Biofilm","volume":"9 ","pages":"Article 100270"},"PeriodicalIF":5.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sucrose reduces biofilm formation by Klebsiella pneumoniae through the PTS components ScrA and Crr","authors":"Yu-Tze Horng ,&nbsp;Chih-Ching Chien ,&nbsp;Novaria Sari Dewi Panjaitan ,&nbsp;Shih-Wen Tseng ,&nbsp;Hsueh-Wen Chen ,&nbsp;Hung-Chi Yang ,&nbsp;Yih-Yuan Chen ,&nbsp;Po-Chi Soo","doi":"10.1016/j.bioflm.2025.100269","DOIUrl":"10.1016/j.bioflm.2025.100269","url":null,"abstract":"<div><div>The presence of sucrose at concentrations of 0.5–5% can either increase bacterial biofilms (<em>Streptococcus mutans</em> and <em>Escherichia coli</em>) or have no significant effect on biofilms (<em>Pseudomonas aeruginosa</em> and <em>Staphylococcus aureus</em>). However, our study revealed that 1 % sucrose reduced the biofilm formation by <em>Klebsiella pneumoniae</em> STU1. To explore the role of the phosphoenolpyruvate-dependent-carbohydrate: phosphotransferase system (PTS) in regulating this process, the <em>scrA</em> gene, which encodes the sucrose-specific EIIBC of the PTS, was deleted in <em>K. pneumoniae</em> to create a <em>scrA</em> mutant (Δ<em>scrA</em>). Thereafter, we observed that the biofilm formation and type 3 fimbriae production were not affected by sucrose in the Δ<em>scrA</em> while sucrose reduced these processes in the wild type. Furthermore, we discovered that Crr, the glucose-specific EIIA of PTS, was the primary but not the sole EIIA of ScrA in <em>K. pneumoniae</em> by sucrose fermentation test. In addition, deficiency of Crr reduced the biofilm formation in <em>K. pneumoniae</em>. Our proposed model suggests that, through the action of Crr in the absence of sucrose, the transcription of the <em>mrk</em> operon, which produces type 3 fimbriae, was increased, thereby influencing biofilm formation by <em>K. pneumoniae</em> and bacterial number in the gut of nematode. This observation differs from the regulation of polysaccharide and biofilm by sucrose in other bacteria. Our findings extend the understanding of the effects of sucrose on biofilm formation.</div></div>","PeriodicalId":55844,"journal":{"name":"Biofilm","volume":"9 ","pages":"Article 100269"},"PeriodicalIF":5.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drosera rotundifolia L. as E. coli biofilm inhibitor: Insights into the mechanism of action using proteomics/metabolomics and toxicity studies","authors":"Sandy Gerschler ,&nbsp;Sandra Maaß ,&nbsp;Philip Gerth ,&nbsp;Lukas Schulig ,&nbsp;Toni Wildgrube ,&nbsp;Jan Rockstroh ,&nbsp;Martina Wurster ,&nbsp;Karen Methling ,&nbsp;Dörte Becher ,&nbsp;Michael Lalk ,&nbsp;Christian Schulze ,&nbsp;Sebastian Guenther ,&nbsp;Nadin Schultze","doi":"10.1016/j.bioflm.2025.100268","DOIUrl":"10.1016/j.bioflm.2025.100268","url":null,"abstract":"<div><div>The successful sustainable cultivation of the well-known medicinal plant sundew on rewetted peatlands not only leads to the preservation of natural populations, but also provides a basis for the sustainable pharmaceutical use of the plant. The bioactive compounds of sundew, flavonoids and naphthoquinones, show biofilm-inhibiting properties against multidrug-resistant, ESBL-producing <em>E. coli</em> strains and open up new therapeutic possibilities.</div><div>This study investigates the molecular mechanisms of these compounds in biofilm inhibition through proteomic analyses. Specific fractions of flavonoids and naphthoquinones, as well as individual substances like 7-methyljuglone and 2″-<em>O</em>-galloylhyperoside, are analyzed. Results show that naphthoquinones appear to act via central regulatory proteins such as OmpR and alter the stress response while flavonoids likely affect biofilm formation by creating an iron-poor environment through iron complexation and additionally influence polyamine balance, reducing intracellular spermidine levels. Further investigations including assays for iron complexation and analysis of polyamines confirmed the proteomic data. Safety evaluations through cytotoxicity tests in 3D cell cultures and the <em>Galleria mellonella in vivo</em> model confirm the safety of the extracts used. These findings highlight sundew as a promising candidate for new phytopharmaceuticals.</div></div>","PeriodicalId":55844,"journal":{"name":"Biofilm","volume":"9 ","pages":"Article 100268"},"PeriodicalIF":5.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From adhesion to biofilms formation and resilience: Exploring the impact of silver nanoparticles-based biomaterials on Pseudomonas aeruginosa","authors":"Maya Rima ,&nbsp;Christina Villeneuve-Faure ,&nbsp;Ludovic Pilloux ,&nbsp;Christine Roques ,&nbsp;Fatima El Garah ,&nbsp;Kremena Makasheva","doi":"10.1016/j.bioflm.2025.100267","DOIUrl":"10.1016/j.bioflm.2025.100267","url":null,"abstract":"<div><div>Colonization of medical devices by microorganisms, often progressing to the formation of resilient biofilms, presents a common clinical issue. To address this challenge, there is growing interest in developing novel biomaterials with antimicrobial/antibiofilm properties as a promising preventive measure. This study explores nanocomposite biomaterials based on silver nanoparticles (AgNPs) deposited on thin silica (SiO₂) layers for their potential effect on the adhesion, detachment, viability and biofilm formation of the opportunistic <em>Pseudomonas aeruginosa</em>. The AgNPs-based biointerface effect on biofilm development is investigated on the PAO1-Tn<em>7</em>-<em>gfp</em> strain by combining experiments under static and dynamic conditions. For the latter, a shear-stress flow chamber is used to mimic conditions encountered around certain medical devices. The findings reveal a rapid bactericidal effect of the AgNPs, noticeable within 30 min of exposure. Moreover, a delay in surface colonization is observed with a thin and unstructured biofilm, even after 72h of dynamic culture. A considerable fragility and sensitivity to hydrodynamic stresses is noticed for this loosely attached bacterial monolayer when compared with the thick and resilient biofilm formed on SiO₂ surface. This study underlines the potential of AgNPs-based biomaterials in the conception of novel antimicrobial/antibiofilm surfaces with controlled release of the biocidal agent.</div></div>","PeriodicalId":55844,"journal":{"name":"Biofilm","volume":"9 ","pages":"Article 100267"},"PeriodicalIF":5.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellulophaga algicola alginate lyase and Pseudomonas aeruginosa Psl glycoside hydrolase inhibit biofilm formation by Pseudomonas aeruginosa CF2843 on three-dimensional aggregates of lung epithelial cells","authors":"Neetu ,&nbsp;Shilpee Pal ,&nbsp;Srikrishna Subramanian ,&nbsp;T.N.C. Ramya","doi":"10.1016/j.bioflm.2025.100265","DOIUrl":"10.1016/j.bioflm.2025.100265","url":null,"abstract":"<div><div><em>Pseudomonas aeruginosa</em> is an opportunistic pathogen that produces a biofilm containing the polysaccharides, alginate, Psl, and Pel, and causes chronic lung infection in cystic fibrosis patients. Others and we have previously explored the use of alginate lyases in inhibiting <em>P. aeruginosa</em> biofilm formation on plastic and lung epithelial cell monolayers. We now employ a more physiologically representative model system, i.e., three-dimensional aggregates of A549 lung epithelial cells cultured under conditions of microgravity in a rotary cell culture system to mimic the natural lung environment, and a previously isolated clinical strain, <em>Pseudomonas aeruginosa</em> CF2843 that we engineered by transposon-mediated integration to express Green Fluorescent Protein and for which we also report the complete genome sequence. Immunostaining and lectin binding studies indicated that the three-dimensional cell aggregates harbored sialylated and fucosylated epitopes as well as Muc1, Muc5Ac, and β-catenin on their surfaces, suggestive of mucin secretion and the presence of tight junctions, hallmark features of lung epithelial tissue. Using this validated model system with confocal microscopy and viable bacterial counts as readouts, we demonstrated that <em>Cellulophaga algicola</em> alginate lyase and <em>Pseudomonas aeruginosa</em> Psl glycoside hydrolase, but not <em>Pseudomonas aeruginosa</em> Pel glycoside hydrolase, inhibit biofilm formation by <em>Pseudomonas aeruginosa</em> on three-dimensional lung epithelial cell aggregates.</div></div>","PeriodicalId":55844,"journal":{"name":"Biofilm","volume":"9 ","pages":"Article 100265"},"PeriodicalIF":5.9,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune-based strategies for the treatment of biofilm infections","authors":"Zachary Van Roy,&nbsp;Tammy Kielian","doi":"10.1016/j.bioflm.2025.100264","DOIUrl":"10.1016/j.bioflm.2025.100264","url":null,"abstract":"<div><div>Biofilms are bacterial communities surrounded by a polymeric matrix that can form on implanted materials and biotic surfaces, resulting in chronic infection that is recalcitrant to immune- and antibiotic-mediated clearance. Therefore, biofilm infections present a substantial clinical challenge, as treatment often involves additional surgical interventions to remove the biofilm nidus, prolonged antimicrobial therapy to clear residual bacteria, and considerable risk of treatment failure or infection recurrence. These factors, combined with progressive increases in antimicrobial resistance, highlight the need for alternative therapeutic strategies to circumvent undue morbidity, mortality, and resource strain on the healthcare system resulting from biofilm infections. One promising option is reprogramming dysfunctional immune responses elicited by biofilm. Here, we review the literature describing immune responses to biofilm infection with a focus on targets or strategies ripe for clinical translation. This represents a complex and dynamic challenge, with context-dependent host-pathogen interactions that differ across infection models, microenvironments, and individuals. Nevertheless, consistencies among these variables exist, which could facilitate the development of immune-based strategies for the future treatment of biofilm infections.</div></div>","PeriodicalId":55844,"journal":{"name":"Biofilm","volume":"9 ","pages":"Article 100264"},"PeriodicalIF":5.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A simulated microgravity biofilm reactor with integrated microfabricated sensors: Advancing biofilm studies in near-space conditions","authors":"Haley M. Ketteler ,&nbsp;Erick L. Johnson ,&nbsp;Matthew McGlennen ,&nbsp;Markus Dieser ,&nbsp;Christine M. Foreman ,&nbsp;Stephan Warnat","doi":"10.1016/j.bioflm.2025.100263","DOIUrl":"10.1016/j.bioflm.2025.100263","url":null,"abstract":"<div><div>Studying biofilms in a microgravity environment currently relies on one of two scenarios, collecting planktonic aggregates in rotating wall vessels or performing experiments in the microgravity environment of space on the International Space Station. While informative techniques, both have their limitations when studying surface-attached microbial communities. A simulated microgravity biofilm reactor (SMBR) was developed to study biofilms in microgravity, coupled with the integration of microfabricated sensors for internal system monitoring. The establishment of simulated microgravity was demonstrated through computational fluid dynamic modelling revealing low fluid shear stress conditions (&lt;1 mPa) throughout the reactor and on the wall surface. Microfabricated resistance temperature devices integrated in the reactor walls confirmed the capability for continuous sensor measurements during operation with the ability to perform traditional microbiology analyses on the sensor surface following an experiment. Microbiological analyses established that there were no significant differences in biofilm growth between sensor and wall surfaces within the reactor. With the integration of defined sampling surfaces, the SMBR allows for in-depth biofilm analysis in a repeatable and accessible manner allowing for a greater understanding of the effects of microgravity on biofilm.</div></div>","PeriodicalId":55844,"journal":{"name":"Biofilm","volume":"9 ","pages":"Article 100263"},"PeriodicalIF":5.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo efficacy of a refillable intrawound drug delivery device in a sheep model of biofilm-compromised open fracture-related infection","authors":"Dustin Williams ,&nbsp;David Rothberg ,&nbsp;Walker Kay ,&nbsp;Lisa Nehring ,&nbsp;Robert Falconer ,&nbsp;Richard Tyler Epperson ,&nbsp;Brooke Kawaguchi ,&nbsp;Carolyn Ardizzone ,&nbsp;Brian Barnum ,&nbsp;Nicholas Ashton","doi":"10.1016/j.bioflm.2025.100262","DOIUrl":"10.1016/j.bioflm.2025.100262","url":null,"abstract":"<div><div>Open fracture-related infection challenges persist in healthcare. From the time open fractures were defined ∼50 years ago, infection rates have gone essentially unchanged. Contributing factors include compromised vasculature, biofilm, and stalled innovations in treatment and prophylaxis. In this study, we engineered and tested the efficacy of a refillable drug delivery device, the Purgo Pouch (Pouch), that sustains local, high dose intrawound antibiotic concentrations in wound sites. We hypothesized that it would manage biofilm-compromised open fracture-related infection better than clinical standards of care. Therapies were tested in a unique sheep model of long bone open fracture-related infection with compromised tissue and biofilm inocula of methicillin-resistant <em>Staphylococcus aureus</em>. Sheep (n = 5/group) were treated with IV vancomycin (10 days), gentamicin-loaded CaSO₄ beads (single application), or the Pouch (10 days) loaded with gentamicin alone or a triple antibiotic combination. At 21 days, sheep were euthanized and microbiological and histological data collected. Results indicated that the Pouch managed infection more effectively, reducing bioburden to &lt;10⁵ colony forming units (CFU)/sample, which was statistically significant compared to clinical standards, which failed to reduce bioburden to below 10⁵ CFU. The hypothesis was supported. The Pouch received Breakthrough Device Designation by the FDA, is being transitioned toward clinical trials, and is a potential solution to the long-standing problem of open fracture-related infection.</div></div>","PeriodicalId":55844,"journal":{"name":"Biofilm","volume":"9 ","pages":"Article 100262"},"PeriodicalIF":5.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early fibrin biofilm development in cardiovascular infections","authors":"Safae Oukrich ,&nbsp;Jane Hong ,&nbsp;Mariël Leon-Grooters ,&nbsp;Wiggert A. van Cappellen ,&nbsp;Johan A. Slotman ,&nbsp;Gijsje H. Koenderink ,&nbsp;Willem J.B. van Wamel ,&nbsp;Moniek P.M. de Maat ,&nbsp;Klazina Kooiman ,&nbsp;Kirby R. Lattwein","doi":"10.1016/j.bioflm.2025.100261","DOIUrl":"10.1016/j.bioflm.2025.100261","url":null,"abstract":"<div><div>The single most common microbe causing cardiovascular infections is <em>Staphylococcus aureus</em> (<em>S. aureus</em>). <em>S. aureus</em> produces coagulase that converts fibrinogen to fibrin, which is incorporated into biofilms. This process aids in adherence to intravascular structures, defense against the host immune system, and resistance to antimicrobial treatment. Despite its significance, fibrin formation in <em>S. aureus</em> biofilms remains poorly understood. Therefore, this study aimed to elucidate the early development of cardiovascular biofilms. Clinically isolated coagulase-positive <em>S. aureus</em> and coagulase-negative <em>Staphylococcus lugdunensis</em> (<em>S. lugdunensis</em>) from patients with cardiovascular infections, and a coagulase mutant <em>S. aureus</em> Δcoa, were grown in tryptic soy broth (TSB), Iscove's Modified Dulbecco's Medium (IMDM), and pooled human plasma, with or without porcine heart valves. Bacterial growth, metabolic activity, and bacterial fibrinogen utilization were measured over 24 h at 37 °C. Time-lapse confocal microscopy was used to visualize and track biofilm development. <em>S. aureus</em> exhibited more growth in TSB and human plasma than <em>S. lugdunensis</em> and <em>S. aureus</em> Δcoa, but showed similar growth in IMDM after 24 h. Peak metabolic activity for all isolates was highest in TSB and lowest in human plasma. The presence of porcine valves caused strain-dependent alterations in time to peak metabolic activity. Confocal imaging revealed fibrin-based biofilm development exclusively in the coagulase-producing <em>S. aureus</em> strains. Between 2 and 6 h of biofilm development, 74.9 % (p = 0.034) of the fibrinogen from the medium was converted to fibrin. Variations in fibrin network porosity and density were observed among different coagulase-producing <em>S. aureus</em> strains. Fibrin formation is mediated by <em>S. aureus</em> coagulase and first strands occurred within 3 h for clinical strains after exposure to human plasma. This study stresses the importance of experimental design given the bacterial changes due to different media and substrates and provides insights into the early pathogenesis of <em>S. aureus</em> cardiovascular biofilms.</div></div>","PeriodicalId":55844,"journal":{"name":"Biofilm","volume":"9 ","pages":"Article 100261"},"PeriodicalIF":5.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding interactions between biofilms and DNA nanoparticles","authors":"Alexandra Sousa ,&nbsp;Rutuparna Kulkarni ,&nbsp;Mona Johannessen ,&nbsp;Thorsten Wohland ,&nbsp;Nataša Škalko-Basnet ,&nbsp;Sybil Obuobi","doi":"10.1016/j.bioflm.2025.100260","DOIUrl":"10.1016/j.bioflm.2025.100260","url":null,"abstract":"<div><div>Biofilms present a great challenge in antimicrobial therapy due to their inherent tolerance to conventional antibiotics, promoting the need for advanced drug delivery strategies that improve therapy. While various nanoparticles (NPs) have been reported for this purpose, DNA-based NPs remain a largely unexploited resource against biofilm-associated infections. To fill this gap and to lay the groundwork for their potential therapeutic exploitation, we investigated the diffusion, penetration, and retention behaviors of three DNA-based nanocarriers —plain or modified—within <em>P. aeruginosa</em> biofilms. Watson-Crick base pairing or hydrophobic interactions mediated the formation of the plain NPs whilst electrostatic interaction enabled optimization of coated NPs via microfluidic mixing. We assessed the interactions of the nanocarriers with biofilm structures via Single Plane Illumination Microscopy – Fluorescence Correlation Spectroscopy (SPIM-FCS) and Confocal Laser Scanning Microscopy (CLSM). We demonstrate the impact of microfluidic parameters on the physicochemical properties of the modified DNA NPs and their subsequent distinct behaviors in the biofilm. Our results show that single stranded DNA micelles (ssDNA micelle) and tetrahedral DNA nanostructures (TDN) had similar diffusion and penetration profiles, whereas chitosan-coated TDN (TDN-Chit) showed reduced diffusion and increased biofilm retention. This is attributable to the relatively larger size and positive surface charge of the TDN-Chit NPs. The study shows first and foremost that DNA can be used as building block in drug delivery for antibiofilm therapeutics. Moreover, the overall behavioral findings are pivotal for the strategic selection of therapeutic agents to be encapsulated within these structures, possibly affecting the treatment efficacy. This research not only highlights the underexplored potential of DNA-based NPs in antibiofilm therapy but also advocates for further studies using different optimization strategies to refine these nanocarrier systems for targeted treatments in biofilm-related infections.</div></div>","PeriodicalId":55844,"journal":{"name":"Biofilm","volume":"9 ","pages":"Article 100260"},"PeriodicalIF":5.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}