Center for Biofilm Engineering (CBE)
Permanent URI for this communityhttps://scholarworks.montana.edu/handle/1/9334
At the Center for Biofilm Engineering (CBE), multidisciplinary research teams develop beneficial uses for microbial biofilms and find solutions to industrially relevant biofilm problems. The CBE was established at Montana State University, Bozeman, in 1990 as a National Science Foundation Engineering Research Center. As part of the MSU College of Engineering, the CBE gives students a chance to get a head start on their careers by working on research teams led by world-recognized leaders in the biofilm field.
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Item High-density targeting of a viral multifunctional nanoplatform to a pathogenic, biofilm-forming bacterium(2007-04) Suci, Peter A.; Berglund, Deborah L.; Liepold, Lars Otto; Brumfield, Susan; Pitts, Betsey; Davison, William M.; Oltrogge, Luke; Hoyt, Kathryn Olivia; Codd, Sarah L.; Stewart, Philip S.; Young, Mark J.; Douglas, TrevorNanomedicine directed at diagnosis and treatment of infections can benefit from innovations that have substantially increased the variety of available multifunctional nanoplatforms. Here, we targeted a spherical, icosahedral viral nanoplatform to a pathogenic, biofilm-forming bacterium, Staphylococcus aureus. Density of binding mediated through specific protein-ligand interactions exceeded the density expected for a planar, hexagonally close-packed array. A multifunctionalized viral protein cage was used to load imaging agents (fluorophore and MRI contrast agent) onto cells. The fluorescence-imaging capability allowed for direct observation of penetration of the nanoplatform into an S. aureus biofilm. These results demonstrate that multifunctional nanoplatforms based on protein cage architectures have significant potential as tools for both diagnosis and targeted treatment of recalcitrant bacterial infections.Item Intracellular distribution of macrophage targeting ferritin–iron oxide nanocomposite(2009-01) Uchida, M.; Willits, Deborah Ann; Muller, Karin; Willis, Ann F.; Jackiw, Larissa; Jutila, Mark A.; Young, Mark J.; Porter, Alexandra E.; Douglas, TrevorIntracellular distribution of iron oxide nanoparticlesincorporated within a ferritin mutant that displays genetically introduced cell-targeted peptides (RGD-4C) on its exterior surface are investigated using scanning transmission electron microscopy with a high-angle annular dark-field detector. The particles (indicated by arrows) internalized into macrophages much more effectively than those with noncell-targeted ferritin.Item A Human ferritin iron oxide nano-composite magnetic resonance contrast agent(2008-11) Uchida, M.; Terashima, Masahiro; Cunningham, Charles H.; Suzuki, Yoriyasu; Willits, Deborah Ann; Willis, Ann F.; Yang, Philip C.; Tsao, Philip S.; McConnell, Michael V.; Young, Mark J.; Douglas, TrevorMacrophages play important roles in the immunological defense system, but at the same time they are involved in inflammatory diseases such as atherosclerosis. Therefore, imaging macrophages is critical to assessing the status of these diseases. Toward this goal, a recombinant human H chain ferritin (rHFn)-iron oxide nano composite has been investigated as an MRI contrast agent for labeling macrophages. Iron oxide nanoparticles in the form of magnetite (or maghemite) with narrow size distribution were synthesized in the interior cavity of rHFn. The composite material exhibited the R2 relaxivity comparable to known iron oxide MRI contrast agents. Furthermore, the mineralized protein cages are readily taken up by macrophages in vitro and provide significant T2* signal loss of the labeled cells. These results encourage further investigation into the development of the rHFn-iron oxide contrast agent to assess inflammatory disease status such as macrophage-rich atherosclerotic plaques in vivo.Item Targeted delivery of a photosensitizer to Aggregatibacter actinomycetemcomitans biofilm(2010-04) Suci, Peter A.; Kang, Sebyung; Gmür, Rudolf; Douglas, Trevor; Young, Mark J.The ability to selectively target specific biofilm species with antimicrobials would enable control over biofilm consortium composition, with medical applications in treatment of infections on mucosal surfaces that are colonized by a mixture of beneficial and pathogenic microorganisms. We functionalized a genetically engineered multimeric protein with both a targeting moiety (biotin) and either a fluorophore or a photosensitizer (SnCe6). Biofilm microcolonies of Aggregatibacter actinomycetemcomitans, a periodontal pathogen, were targeted with the multifunctional dodecamer. Streptavidin was used to couple biotinylated dodecamer to a biotinylated anti-A. actinomycetemcomitans antibody. This modular targeting approach enabled us to increase the loading of photosensitizer onto the cells by a cycle of amplification. Scanning laser confocal microscopy was used to characterize transport of fluorescently tagged dodecamer into the microcolonies and targeting of the cells with biotin-labeled, fluorescently tagged dodecamer. Light-induced activity of the targeted photosensitizer reduced the viability of A. actinomycetemcomitans biofilm, as indicated by membrane permeability to propidium iodide. The functionalized multimeric protein promises to be a useful tool for controlling periodontal biofilm consortia and offers a modular design whereby moieties that target different species can be readily combined with the functionalized protein construct.Item Selective killing of Aggregatibacter actinomycetemcomitans by ciprofloxacin during development of a dual species biofilm with Streptococcus sanguinis(2011-10) Suci, Peter A.; Young, Mark J.Objectives: Periodontal disease is associated with a pathogen-induced transition to a chronic destructive inflammatory response. Since commensals may either passively or actively contribute to immune homeostasis, therapies aimed at selectively reducing the competitive advantage of pathogens may be effective supplements to traditional methods. We developed an in vitro system to grow biofilms composed of the pathogen (Aggregatibacter actinomycetemcomitans) and the commensal (Streptococcus sanguinis). We used the biofilm model to determine the feasibility of selectively killing the pathogen using the fluoroquinolone, ciprofloxacin.Design: Biofilms were exposed to relevant ciprofloxacin doses during the first 24 h of development, with subsequent removal of the ciprofloxacin for a 24 h period. Biofilm growth was assessed by confocal laser scanning microscopy, crystal violet staining and DNA abundance.Results: Exposure to 0.01 mg/L or 0.5 mg/L ciprofloxacin significantly reduced the microcolony size and cell surface density of A. actinomycetemcomitans in the dual species biofilm over a 24 h period whilst allowing uninhibited S. sanguinis biofilm formation. A. actinomycetemcomitans biofilm development was insignificant over a subsequent 24 h period after removal of the ciprofloxacin indicating that A. actinomycetemcomitans cells were killed.Conclusions: A. actinomycetemcomitans residing in a dual species biofilm with the commensal, S. sanguinis can be selectively killed, or at least rendered metabolically inactive, by treatment with ciprofloxacin. The dual species biofilm model will be a useful tool for designing in vivo studies to determine the efficacy of selective killing agents as an adjunct treatment of localized aggressive forms of periodontal disease.Item Aggregatibacter actinomycetemcomitans biofilm killing by a targeted ciprofloxacin prodrug(2013-09) Reeves, Benjamin D.; Young, Mark J.; Grieco, Paul A.; Suci, Peter A.A pH-sensitive ciprofloxacin prodrug was synthesized and targeted against biofilms of the periodontal pathogen Aggregatibacter actinomycetemcomitans (Aa). The dose required to reduce the viability of a mature biofilm of Aa by ∼80% was in the range of ng cm−2 of colonized area (mean biofilm density 2.33 × 109 cells cm−2). A mathematical model was formulated that predicts the temporal change in the concentration of ciprofloxacin in the Aa biofilm as the drug is released and diffuses into the bulk medium. The predictions of the model were consistent with the extent of killing obtained. The results demonstrate the feasibility of the strategy to induce mortality, and together with the mathematical model, provide the basis for design of targeted antimicrobial prodrugs for the topical treatment of oral infections such as periodontitis. The targeted prodrug approach offers the possibility of optimizing the dose of available antimicrobials in order to kill a chosen pathogen while leaving the commensal microbiota relatively undisturbed.