A5103124088- Escherichia coli research studies
- Bacterial Genetics and Biotechnology
- Urinary Tract Infections Management
- Bacterial biofilms and quorum sensing
- Glycosylation and Glycoproteins Research
- Antibiotic Resistance in Bacteria
- Bacteriophages and microbial interactions
- Monoclonal and Polyclonal Antibodies Research
- Gut microbiota and health
- Probiotics and Fermented Foods
- Enzyme Structure and Function
- Biochemical and Structural Characterization
- Protein Structure and Dynamics
- RNA Interference and Gene Delivery
- Vibrio bacteria research studies
- Reproductive tract infections research
- Oral microbiology and periodontitis research
- Transgenic Plants and Applications
- Immune Cell Function and Interaction
- Drug Transport and Resistance Mechanisms
- Microbial Metabolic Engineering and Bioproduction
- Enterobacteriaceae and Cronobacter Research
- Microbial Natural Products and Biosynthesis
- Chemical Reactions and Isotopes
- Computational Drug Discovery Methods
Washington University in St. Louis
2015-2020
College of Wooster
2011
Gram-negative uropathogenic Escherichia coli (UPEC) bacteria are a causative pathogen of urinary tract infections (UTIs). Previously developed antivirulence inhibitors the type 1 pilus adhesin, FimH, demonstrated oral activity in animal models UTI but were found to have limited compound exposure due metabolic instability O-glycosidic bond (O-mannosides). Herein, we disclose that compounds having replaced with carbon linkages had improved stability and inhibitory against FimH. We report on...
Abstract Uropathogenic E. coli (UPEC) employ the mannose‐binding adhesin FimH to colonize bladder epithelium during urinary tract infection (UTI). Previously reported antagonists exhibit good potency and efficacy, but low bioavailability a short half‐life in vivo. In rational design strategy, we obtained an X‐ray structure of lead mannosides then designed with improved drug‐like properties. We show that cyclizing carboxamide onto biphenyl B‐ring aglycone into fused heterocyclic ring,...
ABSTRACT Curli amyloid fibers are produced as part of the extracellular biofilm matrix and composed primarily major structural subunit CsgA. The CsgE chaperone facilitates secretion CsgA through CsgG by forming a cap at base nonameric outer membrane pore. We elucidated series finely tuned nonpolar charge-charge interactions that facilitate oligomerization its ability to transport unfolded for translocation. in vitro is temperature dependent disrupted mutations W48 F79 residues. Using nuclear...
The F9/Yde/Fml pilus, tipped with the FmlH adhesin, has been shown to provide uropathogenic Escherichia coli (UPEC) a fitness advantage in urinary tract infections (UTIs). Here, we used X-ray structure guided design optimize our previously described ortho-biphenyl Gal and GalNAc antagonists such as compound 1 by replacing carboxylate sulfonamide 50. Other groups which can accept H-bonds were also tolerated. We pursued further modifications biphenyl aglycone resulting significantly improved...
Significance Curli are functional amyloids produced on the surface of many gram-negative bacteria. These amyloids, consisting primarily CsgA, involved in cell adhesion, colonization, and biofilm formation. CsgE is a periplasmic accessory protein that plays central role curli biogenesis by its interaction with CsgA pore CsgG. To understand mechanism formation, it critical to determine structure proteins required for their Here, we report atomic solution double mutant CsgE, as determined NMR....
The penultimate reaction in the oxidative degradation of nicotinate (vitamin B3) to fumarate several species aerobic bacteria is hydrolytic deamination maleamate maleate, catalyzed by amidohydrolase (NicF). Although it has been considered a model system for bacterial N-heterocyclic compounds, only recently have gene clusters that encode enzymes this catabolic pathway identified allow detailed investigations concerning structural basis their mechanisms. Here, Bb1774 from Bordetella...
Urinary tract infections (UTI) affect over 150 million individuals worldwide every year. These are associated with significant morbidity and have a sizeable economic impact, $5 billion being spent on UTI treatment in the USA annually. Uropathogenic E. coli (UPEC) responsible for 80% of community aquired UTIs 65% nosocomial UTI. The current standard care is antibiotic therapy. However, 30–50% women experience recurrent (rUTI) despite receiving prevalence single multi‐drug resistant UPEC...
The genes coding the enzymes of aerobic catabolism nicotinic acid in genus Bordetella, bacterial pathogen responsible for certain respiratory diseases mammals, have recently been discerned. A step this 6-step mechanism degradation to fumaric is hydrolytic deamination maleamate malate by amidohydrolase, NicF (EC 3.5.1.107). BB1782 gene from Bordetella bronchiseptica was cloned, expressed E. coli, and resulting His6-tagged recombinant enzyme purified homogeneity affinity chromatography....
Adhesion to biotic and abiotic surfaces is an essential step in the infectious cycle of many human pathogens. To this end, both Gram‐positive Gram‐negative bacteria have developed a variety strategies overcome innate clearance mechanisms persist within host. The expression biogenesis Chaperone‐Usher Pathway (CUP) pili represent one such strategy. In addition mediating formation bacterial biofilms, these proteinaceous extracellular appendages contain, at their tip, two‐domain adhesin that...