A5034077662- Clostridium difficile and Clostridium perfringens research
- Antimicrobial Resistance in Staphylococcus
- Bacteriophages and microbial interactions
- Viral gastroenteritis research and epidemiology
- Helicobacter pylori-related gastroenterology studies
- Toxin Mechanisms and Immunotoxins
- Bacterial Genetics and Biotechnology
- Antibiotic Resistance in Bacteria
- Microscopic Colitis
- Botulinum Toxin and Related Neurological Disorders
- Escherichia coli research studies
- Enterobacteriaceae and Cronobacter Research
- Biochemical and Structural Characterization
- Diphtheria, Corynebacterium, and Tetanus
- Bacterial Infections and Vaccines
- Glycosylation and Glycoproteins Research
- Infections and bacterial resistance
- Microbial infections and disease research
- Biofuel production and bioconversion
- Traumatic Brain Injury and Neurovascular Disturbances
- Retinal Development and Disorders
- Rabies epidemiology and control
- Plant Pathogenic Bacteria Studies
- Genomics and Phylogenetic Studies
- Probiotics and Fermented Foods
University of Sheffield
2016-2025
Florey Institute of Neuroscience and Mental Health
2018-2025
Trinity College Dublin
2007-2018
Imperial College London
2007-2012
Czech Academy of Sciences, Biology Centre
2011
St. James's Hospital
2007
University of Connecticut
1981
ABSTRACT Clostridium difficile is a major cause of chronic antibiotic-associated diarrhea and significant health care-associated pathogen that forms highly resistant infectious spores. Spo0A conserved transcriptional regulator plays key role in initiating sporulation Bacillus species. Here, we use murine model to study the C. spo0A gene during infection transmission. We demonstrate mutant derivatives can intestinal disease but are unable persist within effectively transmit between mice....
Protein translocation across the cytoplasmic membrane is an essential process in all bacteria. The Sec system, comprising at its core ATPase, SecA, and a channel, SecYEG, responsible for majority of this protein transport. Recently, second parallel system has been described number Gram-positive species. This accessory characterized by presence copy energizing SecA2; where it studied, SecA2 subset substrates. In common with many pathogenic species, Clostridium difficile possesses two copies...
Clostridium difficile is the most common cause of antibiotic-associated intestinal infections and a significant morbidity mortality. Infection with C. requires disruption microbiota, commonly by antibiotic usage. Therapeutic intervention largely relies on small number broad-spectrum antibiotics, which further exacerbate dysbiosis leave patient acutely sensitive to reinfection. Development novel targeted therapeutic interventions will require detailed knowledge essential cellular processes,...
Clostridium difficile is an anaerobic, Gram-positive bacterium that can reside as a commensal within the intestinal microbiota of healthy individuals or cause life-threatening antibiotic-associated diarrhea in immunocompromised hosts. C. also form highly resistant spores are excreted facilitating host-to-host transmission. The spo0A gene encodes conserved transcriptional regulator sporulation required for relapsing disease and transmission mice. Here we describe genome-wide approach using...
Abstract Many bacteria and archaea possess a two-dimensional protein array, or S-layer, that covers the cell surface plays crucial roles in physiology. Here, we report crystal structure of SlpA, main S-layer bacterial pathogen Clostridioides difficile , use electron microscopy to study organisation assembly. The SlpA lattice mimics assembly cell, through tiling triangular prisms above wall, interlocked by distinct ridges facing environment. Strikingly, array is very compact, with pores only...
Clostridium difficile expresses a surface layer (S-layer) which coats the of bacterium and acts as an adhesin facilitating interaction with host enteric cells. The S-layer contains high-molecular-weight protein (HMW SLP) its low-molecular-weight partner (LMW SLP). We show that these proteins form tightly associated non-covalent complex, H/L we identify regions both responsible for complex formation. 2.4 A X-ray crystal structure truncated derivative LMW SLP reveals two domains. Domain 1 has...
Summary Clostridium difficile is a nosocomial pathogen that can cause severe gastrointestinal infections. C. encodes family of cell wall proteins, some which are implicated in pathogenesis. Here we have characterized CwpV, the largest member this family. CwpV surface expressed and post‐translationally processed manner analogous to major S‐layer protein SlpA. Expression cwpV phase variable, with approximately 5% cells population expressing under standard laboratory growth conditions. Upstream...
Clostridium difficile is the main cause of antibiotic-associated diarrhea, leading to significant morbidity and mortality putting considerable economic pressure on healthcare systems. Current knowledge molecular basis pathogenesis limited primarily activities regulation two major toxins. In contrast, little known mechanisms used in colonization enteric system. C. expresses a proteinaceous array its cell surface as S-layer, consisting S-layer protein SlpA family homologues, wall (CWP) family....
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 infection has increased in incidence and severity over the past decade, poses a unique threat to human health. However, genetic manipulation of C. remains its infancy bacterium relatively poorly characterised. Low-efficiency conjugation is currently only available method for transfer plasmid DNA into difficile. This practically limiting slowed progress understanding this important pathogen. Conjugation efficiency varies widely between strains, with clinically relevant...
Significance Clostridioides difficile is the leading cause of healthcare-associated diarrhea worldwide following antibiotic treatment. Consequently, there medical need for novel antibacterial agents acting against C. that leave resident microbiota unharmed. The development such narrow-spectrum antibiotics requires precise knowledge mechanisms fine-tune gene expression to orchestrate genomic output at each locus in genome. We address this issue by defining global transcriptome architecture...
Summary Gram‐positive surface proteins can be covalently or non‐covalently anchored to the cell wall and impart important properties on bacterium in respect of envelope organisation interaction with environment. We describe here a mechanism protein anchoring involving tandem CWB 2 motifs found large number Firmicutes. In Clostridium difficile family, we show three repeats CWB2 motif are essential for correct wall. non‐identical cannot substitute each other, as shown by secretion into culture...
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...
The molecular details of phage tail contraction and bacterial cell envelope penetration remain poorly understood are completely unknown for phages infecting bacteria enveloped by proteinaceous S-layers. Here, we reveal the extended contracted atomic structures an intact contractile-tailed (φCD508) that binds to penetrates protective S-layer Gram-positive human pathogen Clostridioides difficile . is unusually long (225 nm), it also notable contracts less than those studied in related...
Clostridium difficile, a leading cause of hospital-acquired infection, possesses dense surface layer (S-layer) that mediates host–pathogen interactions. The key structural components the S-layer result from proteolytic cleavage precursor protein, SlpA, into high- and low-molecular-weight components. Here we report discovery optimization first inhibitors this process in live bacteria their application for probing processing. We also describe design vivo activity-based probes identify protein...
Strains of Clostridium difficile produce a number surface-localized proteins, including the S-layer proteins (SLPs) and other that have suspected roles in pathogenesis. During Third International C. Symposium (Bled, Slovenia, September 2010) discussions were held on standardization nomenclature. Gene designations proposed for large family cell wall are paralogues SLP contain putative binding motifs. This paper summarizes agreed nomenclature, which we hope will be used by research groups...
Endolysin is a phage-encoded cell-wall hydrolase which degrades the peptidoglycan layer of bacterial cell wall. The enzyme often expressed at late stage phage lytic cycle and required for progeny escape. Endolysins bacteriophage that infect Gram-positive bacteria comprises two domains: binding domain (CBD). Although catalytic endolysin relatively well-studied, precise role CBD ambiguous remains controversial. Here, we focus on function from recently isolated Clostridioides difficile phage....
Escherichia coli is the principal gram-negative causative agent of sepsis and meningitis in neonates. The pathogenesis due to E. K1 involves mucosal colonization, transcytosis epithelial cells, survival bloodstream, eventually invasion meninges. last two aspects have been well characterized at a molecular level. Less known about early stages pathogenesis, i.e., adhesion cells. We previously reported that Hek protein causes autoaggregation can mediate adherence Here, we report Hek-mediated...
Escherichia coli is the principal gram-negative causative agent of sepsis and meningitis in neonates. The pathogenesis due to E. K1 involves mucosal colonization, transcytosis epithelial cells, survival blood stream eventually invasion meninges. latter two aspects have been well characterized at a molecular level last decade. Less known about early stages pathogenesis, i.e. adhesion gastrointestinal cells. Here, characterization Hek protein reported, which expressed by neonatal meningitic...
The vascular endothelium is a major target of sepsis-induced events, and endothelial activation accounts for much the pathology sepsis. Urinary tract infections pneumonia caused by Escherichia coli are among most common causing sepsis in both community hospital settings. Currently, there no approved drugs on market to treat underlying pathophysiology aim this study elucidate molecular mechanism which E. induces injury as result attachment.Laboratory research using hemodynamic perfusion ex...