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Heat-Killed Probiotic Bacteria Differentially Regulate Colonic Epithelial Cell Production Of Human Β-Defensin-2: Dependence On Inflammatory Cytokines., N. Habil, W. Abate, J. Beal, A. D. Foey
Heat-Killed Probiotic Bacteria Differentially Regulate Colonic Epithelial Cell Production Of Human Β-Defensin-2: Dependence On Inflammatory Cytokines., N. Habil, W. Abate, J. Beal, A. D. Foey
School of Biomedical Sciences
The inducible antimicrobial peptide human β-defensin-2 (hBD-2) stimulated by pro-inflammatory cytokines and bacterial products is essential to antipathogen responses of gut epithelial cells. Commensal and probiotic bacteria can augment such mucosal defences. Probiotic use in the treatment of inflammatory bowel disease, however, may have adverse effects, boosting inflammatory responses. The aim of this investigation was to determine the effect of selected probiotic strains on hBD-2 production by epithelial cells induced by pathologically relevant pro-inflammatory cytokines and the role of cytokine modulators in controlling hBD-2. Caco-2 colonic intestinal epithelial cells were pre-incubated with heat-killed probiotics, i.e. Lactobacillus casei strain Shirota (LcS) …
Uncoupling Protein-2 Attenuates Palmitoleate Protection Against The Cytotoxic Production Of Mitochondrial Reactive Oxygen Species In Ins-1e Insulinoma Cells., Jonathan Barlow, Jensen V Hirschberg, Charles Affourtit
Uncoupling Protein-2 Attenuates Palmitoleate Protection Against The Cytotoxic Production Of Mitochondrial Reactive Oxygen Species In Ins-1e Insulinoma Cells., Jonathan Barlow, Jensen V Hirschberg, Charles Affourtit
School of Biomedical Sciences
High glucose and fatty acid levels impair pancreatic beta cell function. We have recently shown that palmitate-induced loss of INS-1E insulinoma cells is related to increased reactive oxygen species (ROS) production as both toxic effects are prevented by palmitoleate. Here we show that palmitate-induced ROS are mostly mitochondrial: oxidation of MitoSOX, a mitochondria-targeted superoxide probe, is increased by palmitate, whilst oxidation of the equivalent non-targeted probe is unaffected. Moreover, mitochondrial respiratory inhibition with antimycin A stimulates palmitate-induced MitoSOX oxidation. We also show that palmitate does not change the level of mitochondrial uncoupling protein-2 (UCP2) and that UCP2 knockdown does not …
Human Cytomegalovirus-Encoded Pul7 Is A Novel Ceacam1-Like Molecule Responsible For Promotion Of Angiogenesis., Jason D. Macmaniman, Andrew Meuser, Sara Botto, Patricia P. Smith, Fenyong Liu, Michael A. Jarvis, Jay A. Nelson, Patrizia Caposio
Human Cytomegalovirus-Encoded Pul7 Is A Novel Ceacam1-Like Molecule Responsible For Promotion Of Angiogenesis., Jason D. Macmaniman, Andrew Meuser, Sara Botto, Patricia P. Smith, Fenyong Liu, Michael A. Jarvis, Jay A. Nelson, Patrizia Caposio
School of Biomedical Sciences
UNLABELLED: Persistent human cytomegalovirus (HCMV) infection has been linked to several diseases, including atherosclerosis, transplant vascular sclerosis (TVS), restenosis, and glioblastoma. We have previously shown that factors secreted from HCMV-infected cells induce angiogenesis and that this process is due, at least in part, to increased secretion of interleukin-6 (IL-6). In order to identify the HCMV gene(s) responsible for angiogenesis promotion, we constructed a large panel of replication-competent HCMV recombinants. One HCMV recombinant deleted for UL1 to UL10 was unable to induce secretion of factors necessary for angiogenesis. Fine mapping using additional HCMV recombinants identified UL7 as a viral gene required …
Multiple Metabolomics Of Uropathogenic E. Coli Reveal Different Information Content In Terms Of Metabolic Potential Compared To Virulence Factors., Haitham Alrabiah, Yun Xu, Nicholas J.W. Rattray, Andrew A. Vaughan, Tarek Gibreel, Ali Sayqal, Mathew Upton, J. William Allwood, Royston Goodacre
Multiple Metabolomics Of Uropathogenic E. Coli Reveal Different Information Content In Terms Of Metabolic Potential Compared To Virulence Factors., Haitham Alrabiah, Yun Xu, Nicholas J.W. Rattray, Andrew A. Vaughan, Tarek Gibreel, Ali Sayqal, Mathew Upton, J. William Allwood, Royston Goodacre
School of Biomedical Sciences
No single analytical method can cover the whole metabolome and the choice of which platform to use may inadvertently introduce chemical selectivity. In order to investigate this we analysed a collection of uropathogenic Escherichia coli. The selected strains had previously undergone extensive characterisation using classical microbiological methods for a variety of metabolic tests and virulence factors. These bacteria were analysed using Fourier transform infrared (FT-IR) spectroscopy; gas chromatography mass spectrometry (GC-MS) after derivatisation of polar non-volatile analytes; as well as reversed-phase liquid chromatography mass spectrometry in both positive (LC-MS(+ve)) and negative (LC-MS(-ve)) electrospray ionisation modes. A comparison of the discriminatory …
The Bacterial Skin Microbiome In Psoriatic Arthritis, An Unexplored Link In Pathogenesis: Challenges And Opportunities Offered By Recent Technological Advances., Madhura Castelino, Stephen Eyre, Mathew Upton, Pauline Ho, Anne Barton
The Bacterial Skin Microbiome In Psoriatic Arthritis, An Unexplored Link In Pathogenesis: Challenges And Opportunities Offered By Recent Technological Advances., Madhura Castelino, Stephen Eyre, Mathew Upton, Pauline Ho, Anne Barton
School of Biomedical Sciences
The resident microbial community, harboured by humans in sites such as the skin and gastrointestinal tract, is enormous, representing a candidate environmental factor affecting susceptibility to complex diseases, where both genetic and environmental risk factors are important. The potential of microorganisms to influence the human immune system is considerable, given their ubiquity. The impact of the host-gene-microbe interaction on the maintenance of health and the development of disease has not yet been assessed robustly in chronic inflammatory conditions. PsA represents a model inflammatory disease to explore the role of the microbiome because skin involvement and overlap with IBD implicates both …
The Complete Genome Sequence Of Escherichia Coli Ec958: A High Quality Reference Sequence For The Globally Disseminated Multidrug Resistant E. Coli O25b:H4-St131 Clone., Brian M. Forde, Zakour Nl Ben, Mitchell Stanton-Cook, Minh Duy Phan, Makrina Totsika, Kate M. Peters, Kok Gan Chan, Mark A. Schembri, Mathew Upton, Scott A. Beatson
The Complete Genome Sequence Of Escherichia Coli Ec958: A High Quality Reference Sequence For The Globally Disseminated Multidrug Resistant E. Coli O25b:H4-St131 Clone., Brian M. Forde, Zakour Nl Ben, Mitchell Stanton-Cook, Minh Duy Phan, Makrina Totsika, Kate M. Peters, Kok Gan Chan, Mark A. Schembri, Mathew Upton, Scott A. Beatson
School of Biomedical Sciences
Escherichia coli ST131 is now recognised as a leading contributor to urinary tract and bloodstream infections in both community and clinical settings. Here we present the complete, annotated genome of E. coli EC958, which was isolated from the urine of a patient presenting with a urinary tract infection in the Northwest region of England and represents the most well characterised ST131 strain. Sequencing was carried out using the Pacific Biosciences platform, which provided sufficient depth and read-length to produce a complete genome without the need for other technologies. The discovery of spurious contigs within the assembly that correspond to site-specific …
Galleria Mellonella Infection Model Demonstrates High Lethality Of St69 And St127 Uropathogenic E. Coli., Majed F. Alghoribi, Tarek M. Gibreel, Andrew R. Dodgson, Scott A. Beatson, Mathew Upton
Galleria Mellonella Infection Model Demonstrates High Lethality Of St69 And St127 Uropathogenic E. Coli., Majed F. Alghoribi, Tarek M. Gibreel, Andrew R. Dodgson, Scott A. Beatson, Mathew Upton
School of Biomedical Sciences
Galleria mellonella larvae are an alternative in vivo model for investigating bacterial pathogenicity. Here, we examined the pathogenicity of 71 isolates from five leading uropathogenic E. coli (UPEC) lineages using G. mellonella larvae. Larvae were challenged with a range of inoculum doses to determine the 50% lethal dose (LD50) and for analysis of survival outcome using Kaplan-Meier plots. Virulence was correlated with carriage of a panel of 29 virulence factors (VF). Larvae inoculated with ST69 and ST127 isolates (10(4) colony-forming units/larvae) showed significantly higher mortality rates than those infected with ST73, ST95 and ST131 isolates, killing 50% of the larvae …