A5019422193- Escherichia coli research studies
- Viral gastroenteritis research and epidemiology
- Vibrio bacteria research studies
- Aquaculture disease management and microbiota
- Bacterial Genetics and Biotechnology
- Salmonella and Campylobacter epidemiology
- Clostridium difficile and Clostridium perfringens research
- Gut microbiota and health
- Probiotics and Fermented Foods
- Antibiotic Resistance in Bacteria
- Bacteriophages and microbial interactions
- Evolution and Genetic Dynamics
- bioluminescence and chemiluminescence research
- Marine Toxins and Detection Methods
- Marine Biology and Environmental Chemistry
- Biochemical and Molecular Research
- Signaling Pathways in Disease
- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- Immune Response and Inflammation
- Peptidase Inhibition and Analysis
- Click Chemistry and Applications
- Identification and Quantification in Food
- Child Nutrition and Water Access
- Bacterial biofilms and quorum sensing
University of Surrey
1976-2024
Frederick National Laboratory for Cancer Research
2023-2024
National Cancer Institute
2023-2024
Center for Cancer Research
2023-2024
National Institutes of Health
2023
Boehringer Ingelheim (United States)
2016
Brigham and Women's Hospital
2007-2014
Harvard University
2007-2013
Howard Hughes Medical Institute
2003-2013
Guildford Hospital
2012
Many bacterial pathogens rely on a conserved membrane histidine sensor kinase, QseC, to respond host adrenergic signaling molecules and signals in order promote the expression of virulence factors. Using high-throughput screen, we identified small molecule, LED209, that inhibits binding preventing its autophosphorylation consequently inhibiting QseC-mediated activation gene expression. LED209 is not toxic does inhibit pathogen growth; however, this compound markedly several vitro vivo...
Vibrio parahaemolyticus is a leading cause of seafood-borne gastroenteritis in many parts the world, but there limited knowledge pathogenesis V. parahaemolyticus-induced diarrhea. The absence an oral infection-based small animal model to study intestinal colonization and disease has constrained analyses course infection factors that mediate it. Here, we demonstrate infant rabbits oro-gastrically inoculated with develop severe diarrhea enteritis, main clinical pathologic manifestations...
ABSTRACT In addition to causing diarrhea, Escherichia coli O157:H7 infection can lead hemolytic-uremic syndrome (HUS), a severe disease characterized by hemolysis and renal failure. Differences in HUS frequency among E. outbreaks have been noted, but our understanding of bacterial factors that promote is incomplete. 2006, an outbreak caused consumption contaminated spinach, there was notably high HUS. We sequenced the genome strain responsible (TW14359) with goal identifying candidate...
Global change has caused a worldwide increase in reports of Vibrio-associated diseases with ecosystem-wide impacts on humans and marine animals. In Europe, higher prevalence human infections followed regional climatic trends outbreaks occurring during episodes unusually warm weather. Similar patterns were also observed affecting organisms such as fish, bivalves corals. Basic knowledge is still lacking the ecology evolutionary biology these bacteria well their virulence mechanisms. Current...
ABSTRACT Enteric pathogens such as enterohemorrhagic Escherichia coli (EHEC) and Citrobacter rodentium , which is largely used a surrogate EHEC model for murine infections, are exposed to several host neurotransmitters in the gut. An important chemical exchange within gut involves epinephrine and/or norepinephrine, extensively reported increase virulence gene expression EHEC, acting through two bacterial adrenergic sensors: QseC QseE. However, unable establish itself cause its hallmark...
Enterohemorrhagic Escherichia coli (EHEC) is a group of food-borne pathogens that can cause diarrhea, colitis, and the hemolytic uremic syndrome (HUS). The importance several proposed EHEC virulence factors lacks experimental verification in animal models. limitations current models led us to reexamine infant rabbit model for study pathogenicity. Here, we report intragastric inoculation Shiga toxin 2 (Stx2)-producing E. O157:H7 clinical isolate into rabbits severe diarrhea intestinal...
ABSTRACT Cholera is a severe diarrheal disease, caused by Vibrio cholerae , for which there has been no reproducible, nonsurgical animal model. Here, we report that orogastric inoculation of V. into 3-day-old rabbits pretreated with cimetidine led to lethal, watery diarrhea in virtually all rabbits. The appearance and chemical composition the rabbit fluid were comparable those “rice-water stool” produced cholera patients. As humans, mutants do not produce toxin (CT) toxin-coregulated pilus...
Vibrio parahaemolyticus type III secretion system 2 (T3SS2) is essential for the organism's virulence, but effectors required intestinal colonization and induction of diarrhea by this pathogen have not been identified. Here, we identify a (T3SS2)-secreted effector, VopZ, that V. pathogenicity. VopZ plays distinct, genetically separable roles in enabling diarrheagenesis. Truncation prevents colonization, whereas deletion amino acids 38-62 abrogates parahaemolyticus-induced pathology does...
ABSTRACT Cholera is a severe diarrheal disease typically caused by O1 serogroup strains of Vibrio cholerae . The pathogenicity all pandemic V. relies on two critical virulence factors: cholera toxin, potent enterotoxin, and toxin coregulated pilus (TCP), an intestinal colonization factor. However, certain non-O1, non-O139 strains, such as AM-19226, do not produce or TCP, yet they still cause diarrhea. molecular basis for the has been extensively characterized, but many these encode related...
Abstract Background Escherichia coli is an opportunistic pathogen which colonizes various host species. However, to what extent genetic lineages of E. are adapted or restricted specific hosts and the genomic determinants such adaptation restriction poorly understood. Results We randomly sampled isolates from four countries (Germany, UK, Spain, Vietnam), obtained five species (human, pig, cattle, chicken, wild boar) over 16 years, both healthy diseased hosts, construct a collection 1198...
Strategies to target specific protein cysteines are critical covalent probe and drug discovery. 3-Bromo-4,5-dihydroisoxazole (BDHI) is a natural product-inspired, synthetically accessible electrophilic moiety that has previously been shown react with nucleophilic in the active site of purified enzymes. Here, we define global cysteine reactivity selectivity set BDHI-functionalized chemical fragments using competitive chemoproteomic profiling methods. Our study demonstrates BDHIs capably...
ABSTRACT The genes encoding the enterohemorrhagic Escherichia coli (EHEC) type III secretion system (TTSS) and five effector proteins secreted by TTSS are located on locus of enterocyte effacement (LEE) pathogenicity island. Deletion tir , which encodes one these proteins, results in a profound reduction (∼10,000-fold) EHEC colonization infant rabbit intestine, but vivo phenotypes other LEE unknown. Here, we constructed in-frame deletions escN putative ATPase component TTSS, four LEE-encoded...
ABSTRACT AvR2-V10.3 is an engineered R-type pyocin that specifically kills Escherichia coli O157, enteric pathogen a major cause of food-borne diarrheal disease. New therapeutics to counteract E. O157 are needed, as currently available antibiotics can exacerbate the consequences infection. We show here orogastric administration prevent or ameliorate O157:H7-induced diarrhea and intestinal inflammation in infant rabbit model infection when compound administered either postexposure...
Classical studies have focused on the role that individual regulators play in controlling virulence gene expression. An emerging theme, however, is bacterial metabolism also plays a key this process. Our previous work identified series of proteins were implicated regulation virulence. One these was AdhE, bi-functional acetaldehyde-CoA dehydrogenase and alcohol dehydrogenase. Deletion its (adhE) resulted elevated levels extracellular acetate stark pleiotropic phenotype: strong suppression...
Cholera remains a major risk in developing countries, particularly after natural or man-made disasters. Vibrio cholerae El Tor is the most important cause of these outbreaks, and becoming increasingly resistant to antibiotics, so alternative therapies are urgently needed. In this study, single bacteriophage, Phi_1, was used control cholera prophylactically therapeutically an infant rabbit model. both cases, phage-treated animals showed no clinical signs disease, compared with 69% untreated...
ABSTRACT There is considerable diversity among Shiga toxin (Stx)-producing Escherichia coli (STEC) bacteria, and only a subset of these organisms are thought to be human pathogens. The characteristics that distinguish STEC bacteria give rise disease not well understood. Stxs, the principal virulence determinants STEC, account for hemolytic-uremic syndrome (HUS), severe clinical consequence infection. Stxs typically bacteriophage encoded, their production has been shown enhanced by...
Enterohemorrhagic Escherichia coli (EHEC) is a noninvasive food-borne pathogen that colonizes the distal ileum and colon. Proteins encoded in EHEC locus of enterocyte effacement (LEE) pathogenicity island are known to contribute this pathogen's adherence epithelial cells intestinal colonization. The role non-LEE-encoded proteins these processes not as clear. We found Z2053 gene (designated adfO here), located cryptic prophage, exhibits similarity and/or colonization factor genes several...
Cholera is a severe diarrheal disease caused by the motile Gram-negative rod Vibrio cholerae. Live-attenuated V. cholerae vaccines harboring deletions of genes encoding cholera toxin have great promise for reducing global burden cholera. However, development live has been hampered tendency such strains to induce noncholeric reactogenic diarrhea in human subjects. The molecular bases reactogenicity are unknown, but it speculated that response cholerae's flagellum and/or motility enables....
ABSTRACT A chromosomally lux- marked (Tn 5 luxCDABE ) strain of nontoxigenic Escherichia coli O157:H7 was constructed by transposon mutagenesis and shown to have retained the O157, H7, intimin phenotypes . The survival characteristics this in experiments performed (soil at −5, −100, −1,500 kPa matric potential artificial groundwater) were indistinguishable from wild-type strain. Evaluation luminescence found be a rapid, cheap, quantitative measure viable E. Tn populations environmental...
ABSTRACT We assessed the ability of a kanamycin-marked Stx phage to move into commensal, ovine Escherichia coli strain in ruminant gastrointestinal tract. Transduction was detected 19/24 sheep tested, resulting recovery 47 transductants. Subtherapeutic doses quinolone antibiotic enrofloxacin did not increase rate transduction.