A5072491565- Bacterial biofilms and quorum sensing
- Oral microbiology and periodontitis research
- Bacteriophages and microbial interactions
- Bacterial Genetics and Biotechnology
- Advanced NMR Techniques and Applications
- Antifungal resistance and susceptibility
- Vibrio bacteria research studies
- Cystic Fibrosis Research Advances
- Microbial Community Ecology and Physiology
- Polymer Surface Interaction Studies
- Bacterial Identification and Susceptibility Testing
- Inhalation and Respiratory Drug Delivery
- RNA and protein synthesis mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Biochemical and Structural Characterization
- Chemical Synthesis and Characterization
- Porphyrin Metabolism and Disorders
- Microbial Natural Products and Biosynthesis
- Biofuel production and bioconversion
- Nanopore and Nanochannel Transport Studies
- Bacterial Infections and Vaccines
- Legionella and Acanthamoeba research
- Advanced Cellulose Research Studies
- Gut microbiota and health
University of Washington
2018-2025
Washington University in St. Louis
2023-2024
Stanford University
2011-2018
Montana State University
2009-2011
Abstract Pseudomonas aeruginosa biofilms are composed of exopolysaccharides (EPS), exogenous DNA, and proteins that hold these communities together. P. produces lectins LecA LecB, which possess affinities towards sugars found in matrix EPS mediate adherence to target host cells. Here, we demonstrate LecB binds Psl, a key EPS, this leads increased retention both cells growing biofilm. This interaction is predicted occur between the lectin branched side chains present on Psl. Finally, show...
In cystic fibrosis (CF) airways, Pseudomonas aeruginosa forms cellular aggregates called biofilms that are thought to contribute chronic infection. To form aggregates, P. can use different mechanisms, each with its own pathogenic implications. However, how they in vivo is controversial and unclear. One mechanism involves a bacterially produced extracellular matrix holds the together. Pel Psl exopolysaccharides structural protective components of this matrix. We develop an immunohistochemical...
Packed and ready to go: A scaffold protein (SP) aids the assembly of Salmonella typhimuriam bacteriophage P22 into a capsid, with encapsulation SP. This natural process was exploited by using an engineered molecular system fuse fluorescent cargo (green in picture) portion SP (yellow), which templated accurate spontaneous assembly. Heating capsids treatment thrombin released but not cargo.
Biofilms are robust multicellular aggregates of bacteria that encased in an extracellular matrix. Different bacterial species have been shown to use a range biopolymers build their matrices. Pseudomonas aeruginosa is model organism for the laboratory study biofilms, and past work has suggested exopolysaccharides required matrix component. However, we found expression protein CdrA, absence biofilm exopolysaccharides, allowed formation through production CdrA-rich proteinaceous This represents...
ABSTRACT Pseudomonas aeruginosa produces an extracellular biofilm matrix that consists of nucleic acids, exopolysaccharides, lipid vesicles, and proteins. In general, the protein component is poorly defined understudied relative to other major constituents. While proteins have been suggested provide many functions biofilm, only play a structural role characterized thus far. Here we identify enriched in P. biofilms. We then focused on candidate protein, serine protease inhibitor ecotin...
Pseudomonas aeruginosa is an important pathogen that causes chronic infections involve multicellular aggregates called biofilms. Within biofilms, bacteria are surrounded in a protective extracellular matrix of proteins, exopolysaccharides (EPS), and DNA. A key P. protein adhesin CdrA, which promotes aggregation by binding to the EPS Psl via CdrA-CdrA interactions. We hypothesized because its ability bind Psl, CdrA would be only for strains use as primary (e.g., laboratory strain PAO1). Thus,...
Abstract The genetic capacity to synthesize the biofilm matrix exopolysaccharide Pel is widespread among Gram-negative and Gram-positive bacteria. However, its exact chemical structure has been challenging determine. Using a Pseudomonas aeruginosa strain engineered overproduce Pel, improvements isolation procedure, selective hydrolysis with glycoside hydrolase PelA h , we demonstrate that partially de- N- acetylated linear polymer of α-1,4- acetylgalactosamine comprised predominantly dimeric...
Pel exopolysaccharide biosynthetic loci are phylogenetically widespread biofilm matrix determinants in bacteria. In Pseudomonas aeruginosa, is crucial for cell-to-cell interactions and reducing susceptibility to antibiotic mucolytic treatments. While genes encoding glycoside hydrolases have long been linked biosynthesis, their physiological role development unclear. Here we demonstrate that the hydrolase activity of P. aeruginosa PelA decreases adherent biomass responsible generating low...
Microorganisms produce functional amyloids that can be examined and manipulated in vivo vitro. Escherichia coli assemble extracellular adhesive amyloid fibers termed curli mediate adhesion promote biofilm formation. We have characterized the dye binding properties of hallmark dye, Congo red, with curliated E. isolated fibers. red binds to whole cells, does not inhibit growth, used comparatively quantify whole-cell curliation. Using Surface Plasmon Resonance, we measured dissociation kinetics...
ABSTRACT Aspergillus fumigatus is commonly responsible for lethal fungal infections among immunosuppressed individuals. A. forms biofilm communities that are of increasing biomedical interest due to the association biofilms with chronic and their increased resistance antifungal agents host immune factors. Understanding composition microbial extracellular matrix important understanding function and, ultimately, developing strategies inhibit formation. We implemented a solid-state nuclear...
The exopolysaccharide Psl contributes to biofilm structure and antibiotic tolerance may play a role in the failure eradicate Pseudomonas aeruginosa from cystic fibrosis (CF) airways. study objective was determine whether there were any differences P. isolates that successfully eradicated compared those persisted, despite inhaled tobramycin treatment, children with CF. Initial collected CF undergoing eradication grown as biofilms labeled 3 anti-Psl monoclonal antibodies (Cam003/Psl0096,...
Bacteria form multicellular aggregates called biofilms. A crucial component of these is a protective matrix that holds the community together. Biofilm composition varies depending upon bacterial species but typically includes exopolysaccharides (EPS), proteins, and extracellular DNA. Pseudomonas aeruginosa model organism for study biofilms, in non-mucoid it uses structurally distinct EPS Psl Pel, EPS-binding protein CdrA, eDNA as key components. An interesting phenomenon we others have...
Bacteria associate with surfaces and one another by elaborating an extracellular matrix to encapsulate cells, creating communities termed biofilms. Biofilms are beneficial in some ecological niches, but also contribute the pathogenesis of serious chronic infectious diseases. New approaches quantitative measurements needed define composition architecture bacterial biofilms help drive development strategies interfere biofilm assembly. Solid-state NMR is uniquely suited examination insoluble...
Biomimetic chemistry offers new approaches to supramolecular materials synthesis and assembly. We have demonstrated that an assembled viral protein cage, comprising organic core–shell structure, can be used as a template for the size constrained of Fe2O3. Particle nucleation is directed by inner scaffold layer, while constraints are determined outer capsid layer.
Protein cages such as ferritins and virus capsids have been used containers to synthesize a wide variety of protein-templated inorganic nanoparticles. While identification the crystal phase has successful in some cases, very little is known about detailed nanoscale structure component. We pair distribution function analysis total X-ray scattering measure crystalline domain size nanoparticles ferrihydrite, γ-Fe2O3, Mn3O4, CoPt, FePt grown inside 24-meric ferritin from H. sapiens P. furiosus....
Biofilms are one of the most challenging obstacles in bacterial infections. By providing protection against immune responses and antibiotic therapies, biofilms enable chronic colonization development resistance. As previous clinical observations studies have shown, traditional therapy alone cannot effectively treat eliminate biofilm forming infections due to conferred by biofilm. A new strategy specifically targeting must be developed. Here, we target bind PAO1 elucidate molecular mechanism...
The Congo red derivative (E,E)-1-fluoro-2,5-bis(3-hydroxycarbonyl-4-hydroxy) styrylbenzene (FSB) specifically stains the functional amyloid curli in Escherichia coli biofilms. FSB binds to with similar affinity as red, yet exhibits much greater fluorescence upon binding compared and does not exhibit undesired cellulosic component of biofilm. Thus, presents a powerful tool identify visualize E. biofilms also enables new biophysical investigations curli.