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Browsing by Author "Stoodley, Paul"

Now showing 1 - 4 of 4
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    Bayesian estimation of Pseudomonas aeruginosa viscoelastic properties based on creep responses of wild type, rugose, and mucoid variant biofilms
    Nooranidoost, Mohammad; Cogan, N. G.; Stoodley, Paul; Gloag, Erin S.; Hussaini, M. Yousuff (Elsevier, 2023-06-03)
    Pseudomonas aeruginosa biofilms are relevant for a variety of disease settings, including pulmonary infections in people with cystic fibrosis. Biofilms are initiated by individual bacteria that undergo a phenotypic switch and produce an extracellular polymeric slime (EPS). However, the viscoelastic characteristics of biofilms at different stages of formation and the contributions of different EPS constituents have not been fully explored. For this purpose, we develop and parameterize a mathematical model to study the rheological behavior of three biofilms — P. aeruginosa wild type PAO1, isogenic rugose small colony variant (RSCV), and mucoid variant biofilms against a range of experimental data. Using Bayesian inference to estimate these viscoelastic properties, we quantify the rheological characteristics of the biofilm EPS. We employ a Monte Carlo Markov Chain algorithm to estimate these properties of P. aeruginosa variant biofilms in comparison to those of wild type. This information helps us understand the rheological behavior of biofilms at different stages of their development. The mechanical properties of wild type biofilms change significantly over time and are more sensitive to small changes in their composition than the other two mutants.
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    A Combination of Zinc and Arginine Disrupt the Mechanical Integrity of Dental Biofilms
    Gloag, Erin S.; Khosravi, Yalda; Masters, James G.; Wozniak, Daniel J.; Amorin Daep, Carlo; Stoodley, Paul (American Society for Microbiology, 2022-12-06)
    Mechanical cleaning remains the standard of care for maintaining oral hygiene. However, mechanical cleaning is often augmented with active therapeutics that further promote oral health. A dentifrice, consisting of the "Dual Zinc plus Arginine" (DZA) technology, was found to be effective at controlling bacteria using in vitro laboratory studies, translating to clinical efficacy to deliver plaque and gingivitis reduction benefits. Here, we used biophysical analyses and confocal laser scanning microscopy to understand how a DZA dentifrice impacted the mechanical properties of dental plaque biofilms and determine if changes to biofilm rheology enhanced the removal of dental plaque. Using both uniaxial mechanical indentation and an adapted rotating-disc rheometry assay, it was found that DZA treatment compromised biofilm mechanical integrity, resulting in the biofilm being more susceptible to removal by shear forces compared to treatment with either arginine or zinc alone. Confocal laser scanning microscopy revealed that DZA treatment reduced the amount of extracellular polymeric slime within the biofilm, likely accounting for the reduced mechanical properties. We propose a model where arginine facilitates the entry of zinc into the biofilm, resulting in additive effects of the two activities toward dental plaque biofilms. Together, our results support the use of a dentifrice containing Dual Zinc plus Arginine as part of daily oral hygiene regimens. IMPORTANCE Mechanical removal of dental plaque is augmented with therapeutic compounds to promote oral health. A dentifrice containing the ingredients zinc and arginine has shown efficacy at reducing dental plaque both in vitro and in vivo. However, how these active compounds interact together to facilitate dental plaque removal is unclear. Here, we used a combination of biophysical analyses and microscopy to demonstrate that combined treatment with zinc and arginine targets the matrix of dental plaque biofilms, which destabilized the mechanical integrity of these microbial communities, making them more susceptible to removal by shear forces.
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    Glycoside hydrolase processing of the Pel polysaccharide alters biofilm biomechanics and Pseudomonas aeruginosa virulence
    Razvi, Erum; Whitfield, Gregory B.; Reichhardt, Courtney; Dreifus, Julia E.; Willis, Alexandra R.; Gluscencova, Oxana B.; Gloag, Erin S.; Awad, Tarek S.; Rich, Jacquelyn D.; da Silva, Daniel Passos; Bond, Whitney; Le Mauff, Francois; Sheppard, Donald C.; Hatton, Benjamin D.; Stoodley, Paul; Reinke, Aaron W.; Boulianne, Gabrielle L.; Wozniak, Daniel J.; Harrison, Joe J.; Parsek, Matthew R.; Howell, P. Lynne (Nature Portfolio, 2023-02-02)
    Pel exopolysaccharide biosynthetic loci are phylogenetically widespread biofilm matrix determinants in bacteria. In Pseudomonas aeruginosa, Pel is crucial for cell-to-cell interactions and reducing susceptibility to antibiotic and mucolytic treatments. While genes encoding glycoside hydrolases have long been linked to biofilm exopolysaccharide biosynthesis, their physiological role in biofilm development is unclear. Here we demonstrate that the glycoside hydrolase activity of P. aeruginosa PelA decreases adherent biofilm biomass and is responsible for generating the low molecular weight secreted form of the Pel exopolysaccharide. We show that the generation of secreted Pel contributes to the biomechanical properties of the biofilm and decreases the virulence of P. aeruginosa in Caenorhabditis elegans and Drosophila melanogaster. Our results reveal that glycoside hydrolases found in exopolysaccharide biosynthetic systems can help shape the soft matter attributes of a biofilm and propose that secreted matrix components be referred to as matrix associated to better reflect their influence.
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    Z-form extracellular DNA is a structural component of the bacterial biofilm matrix
    Buzzo, John R.; Devaraj, Aishwarya; Gloag, Erin S.; Jurcisek, Joseph A.; Robledo-Avila, Frank; Kesler, Theresa; Wilbanks, Kathryn; Mashburn-Warren, Lauren; Balu, Sabarathnam; Wickham, Joseph; Novotny, Laura A.; Stoodley, Paul; Bakaletz, Lauren O.; Goodman, Steven D. (Elsevier, 2021-11-11)
    Biofilms are community architectures adopted by bacteria inclusive of a self-formed extracellular matrix that protects resident bacteria from diverse environmental stresses and, in many species, incorporates extracellular DNA (eDNA) and DNABII proteins for structural integrity throughout biofilm development. Here, we present evidence that this eDNA-based architecture relies on the rare Z-form. Z-form DNA accumulates as biofilms mature and, through stabilization by the DNABII proteins, confers structural integrity to the biofilm matrix. Indeed, substances known to drive B-DNA into Z-DNA promoted biofilm formation whereas those that drive Z-DNA into B-DNA disrupted extant biofilms. Importantly, we demonstrated that the universal bacterial DNABII family of proteins stabilizes both bacterial- and host-eDNA in the Z-form in situ. A model is proposed that incorporates the role of Z-DNA in biofilm pathogenesis, innate immune response, and immune evasion.