- Clostridium difficile and Clostridium perfringens research
- Gut microbiota and health
- Microscopic Colitis
- Viral gastroenteritis research and epidemiology
- Salmonella and Campylobacter epidemiology
- Gastrointestinal motility and disorders
- Antibiotic Resistance in Bacteria
- Helicobacter pylori-related gastroenterology studies
- Nosocomial Infections in ICU
- Antimicrobial Resistance in Staphylococcus
- Dermatology and Skin Diseases
- Vibrio bacteria research studies
- Acne and Rosacea Treatments and Effects
- Periodontal Regeneration and Treatments
- Wound Healing and Treatments
- Diamond and Carbon-based Materials Research
- Antibiotic Use and Resistance
- Bacterial Genetics and Biotechnology
- Bacterial biofilms and quorum sensing
- Crystallography and molecular interactions
- Veterinary medicine and infectious diseases
- Crystallization and Solubility Studies
- Liver Disease Diagnosis and Treatment
- Liver Disease and Transplantation
- Retinoids in leukemia and cellular processes
University of Leeds
1999-2024
Bellevue College
2021
Oxford University Press (United Kingdom)
2021
Sisters of Mercy Health System
2021
Royal Adelaide Hospital
2021
Shanghai Institute of Hematology
2021
University Prep
2021
University of Glasgow
2011-2019
Beaumont Hospital
2018
Institute for Molecular Medicine
2017
The microbiome dysbiosis caused by antibiotic treatment has been associated with both susceptibility to and relapse of Clostridium difficile infection (CDI). Bacteriophage (phage) therapy offers target specificity dose amplification in situ, but few studies have focused on its use CDI treatment. This mainly reflects the lack strictly virulent phages that this pathogen. While it is widely accepted temperate are unsuitable for therapeutic purposes due their transduction potential, analysis...
Epidermal growth factor (EGF) is a potent mitogen in vitro, but its biological role less clear. The vulnerary effects of EGF were evaluated model wound repair, the polyvinyl alcohol sponge implanted subcutaneously rats. was purified to homogeneity by reverse-phase HPLC and quantified receptor binding assay amino acid analysis. Preliminary data showed moderate promotion granulation tissue formation daily injections 10 micrograms EGF. To test hypothesis that long-term exposure required for...
The ability of an isogenic set mutants Salmonella enterica serovar Typhimurium L354 (SL1344) with defined deletions in genes encoding components tripartite efflux pumps, including acrB, acrD, acrF and tolC, to colonize chickens was determined competition L354. In addition, the each mutant adhere to, invade, human embryonic intestine cells mouse monocyte macrophages vitro. tolC acrB knockout were hyper-susceptible a range antibiotics, dyes detergents; also more susceptible acid pH bile grew...
ABSTRACT Salmonella enterica isolates ( n = 182) were examined for mutations in the quinolone resistance-determining region of gyrA , gyrB parC and parE . The frequency, location, type GyrA substitution varied with serovar. Mutations found that encoded Thr57-Ser, Thr66-Ile, Ser80-Arg substitutions. located at codon Tyr420-Cys or Arg437-Leu. Novel also encoding Glu453-Gly, His461-Tyr, Ala498-Thr, Val512-Gly, Ser518-Cys. Although it is counterintuitive, a mutation both more susceptible to...
Cartilage-derived growth factor (CDGF), a cationic polypeptide of approximately 18,000 mol wt, was prepared from bovine articular cartilage; other sources were and human scapular costal cartilage. Previous studies have shown that CDGF stimulates the proliferation cultured mouse fibroblasts as well chondrocytes endothelial cells various sources. In this study, to stimulate dose-dependently accumulation DNA collagen by rat embryo population derived granulation tissue. also stimulated capillary...
Chickens, pigs, and cattle are key reservoirs of Salmonella enterica, a foodborne pathogen worldwide importance. Though decade has elapsed since publication the first genome, thousands genes remain hypothetical or unknown function, basis colonization reservoir hosts is ill-defined. Moreover, previous surveys role in vivo have focused on systemic virulence murine typhoid models, genetic intestinal persistence thus zoonotic transmission received little study. We therefore screened pools random...
Nosocomial infections are increasingly being recognised as a major patient safety issue. The modern hospital environment and associated health care practices have provided niche for the rapid evolution of microbial pathogens that well adapted to surviving proliferating in this setting, after which they can infect susceptible patients. This is clearly case bacterial such Methicillin Resistant Staphylococcus aureus (MRSA) Vancomycin Enterococcus (VRE) species, both acquired resistance...
Keratinocytes produce a molecule, epidermal-derived thymocyte activating factor (ETAF), which is biologically and physiochemically similar to the polypeptide hormone interleukin 1 (IL-1). Because stratum corneum (SC) composed of terminally differentiated keratinocytes, we questioned whether ETAF/IL-1 could be isolated from this tissue. The extraction normal human SC with physiologic saline solution yielded large amount activity, as measured by in vitro co-stimulator assay. SC-derived...
Abstract C. difficile infection (CDI) is a worldwide healthcare problem with ~30% of cases failing primary therapy, placing burden on systems and increasing patient morbidity. We have little understanding why these therapies fail. Here, we use clinically validated in vitro gut model to assess the contribution biofilms towards recurrent disease investigate biofilm microbiota- interactions. Initial experiments show that cells became associated colonic microbiota are not depleted by vancomycin...
It has been proposed that lack of a functional efflux system(s) will lead to lower frequency selection resistance fluoroquinolones and other antibiotics. We constructed five strains Salmonella enterica serovar Typhimurium SL1344 lacked gene components nodulation cell division pumps (acrB, acrD, acrF, acrBacrF, tolC) plus three genes effect expression (marA, soxS, ramA) hypermutable strain (mutS::aph). Strains were exposed ciprofloxacin at 2x the MIC in agar, presence absence...
Rare Clostridium difficile mutants lacking surface-layer protein A escape killing by Avidocin-CDs and display severe phenotypic defects that compromise virulence in animals.
Clostridium difficile is the main cause of antibiotic-associated disease, a disease high socio-economical importance that has recently been compounded by global spread 027 (BI/NAP1/027) ribotype. C. cases attributed to ribotype strains have recurrence rates (up 36 %) and increased severity. The hamster model infection widely accepted as an appropriate for studying aspects host–pathogen interactions. Using this we characterized kinetics UK 2006 outbreak strain, R20291. Hamsters were orally...
Abstract The uses of fluorescent reporters derived from green protein have proved invaluable for the visualisation biological processes in bacteria grown under aerobic conditions. However, their requirement oxygen has limited application obligate anaerobes such as Clostridium difficile . Fluorescent proteins Light, Oxygen or Voltage sensing (LOV) domains been shown to bridge this limitation, but utility translational fusions monitor expression and localisation a strict anaerobic bacterium...
Summary C lostridium difficile is a prominent nosocomial pathogen, proliferating and causing enteric disease in individuals with compromised gut microflora. We characterized the post‐translational modification of flagellin . 630. The structure was solved by nuclear magnetic resonance shown to contain an N ‐acetylglucosamine substituted phosphorylated ‐methyl‐ l ‐threonine. A reverse genetics approach investigated function putative four‐gene locus. All mutants were found have truncated glycan...
BackgroundClostridium difficile ribotype-027, ribotype-078, and ribotype-017 are virulent epidemic lineages. Trehalose metabolism variants in these ribotypes, combined with increased human trehalose consumption, have been hypothesised to contributed their emergence virulence.Methods5232 previously whole-genome sequenced C. isolates were analysed. Clinical used investigate the impact of on mortality. Import data estimate changes dietary trehalose. Ribotype-027 virulence was investigated a...
Treatment for moderate-to-severe acne vulgaris relies on prolonged use of oral tetracycline-class antibiotics; however, these broad-spectrum antibiotics are often associated with off-target effects and negative gastrointestinal sequelae. Sarecycline is a narrow-spectrum antibiotic treatment option. Here, we investigated the effect sarecycline exposure, compared tetracyclines (doxycycline minocycline) upon colonic microbiota. Three in vitro models human colon were instilled either...
Salmonella enterica is a facultative intracellular pathogen of worldwide importance. Over 2,500 serovars exist and infections in humans animals may produce spectrum symptoms from enteritis to typhoid depending on serovar- host-specific factors. S. Enteritidis the most prevalent non-typhoidal serovar isolated with acute diarrhoeal illness many countries. Human are frequently associated direct or indirect contact contaminated poultry meat eggs owing ability organism persist avian intestinal...
Clostridium difficile is a spore-forming bacterium that can reside in animals and humans. C. infection causes variety of clinical symptoms, ranging from diarrhea to fulminant colitis. Disease mediated by TcdA TcdB, two large enterotoxins released during colonization the gut. In this study, we evaluated ability recombinant toxin fragments induce neutralizing antibodies mice. The protective efficacies most promising candidates were then hamster model disease. While limited protection was...
A clinically reflective model of the human colon was used to investigate effects broad-spectrum antibiotic omadacycline on gut microbiome and subsequent potential induce simulated Clostridium difficile infection (CDI). Triple-stage chemostat models were inoculated with pooled fecal slurry from healthy volunteers (age, ≥60 years). Models challenged twice 107 CFU C. spores (PCR ribotype 027). Omadacycline assessed in a single model. Observations confirmed parallel study moxifloxacin....
Within the human intestinal tract, dietary, microbial- and host-derived compounds are used as signals by many pathogenic organisms, including Clostridioides difficile . Trehalose has been reported to enhance virulence of certain C. ribotypes; however, such variants widespread not correlated with clinical outcomes for patients suffering from infection (CDI). Here, we make preliminary observations on how trehalose supplementation affects microbiota in an vitro model show that trehalose-induced...
In vitro models of the human colon have been used extensively in understanding gut microbiome (GM) and evaluating how internal external factors affect residing bacterial populations. Such shown to be highly predictive vivo outcomes a number advantages over animal models. The complexity required by closely mimic physiology poses practical limits on their scalability. scalable Mini Gut (MiGut) platform presented this paper allows considerable expansion model replicates enables complex study...
Clostridium difficile is a major cause of antibiotic associated diarrhea. Recently, we have shown that effective protection can be mediated in hamsters through the inclusion specific recombinant fragments from toxin A and B systemically delivered vaccine. Interestingly while neutralizing antibodies to binding domains both are moderately protective, enhanced survival observed when glucosyltransferase region replace those domain this toxin. In addendum, discuss additional information has been...