A5005042071- Pneumonia and Respiratory Infections
- Bacterial Infections and Vaccines
- Pneumocystis jirovecii pneumonia detection and treatment
- Streptococcal Infections and Treatments
- Inflammasome and immune disorders
- Antimicrobial Resistance in Staphylococcus
- Respiratory viral infections research
- Blood disorders and treatments
- Neonatal Health and Biochemistry
- Hemoglobinopathies and Related Disorders
- T-cell and Retrovirus Studies
- Antibiotics Pharmacokinetics and Efficacy
- Legume Nitrogen Fixing Symbiosis
- Immune Cell Function and Interaction
- Renal Diseases and Glomerulopathies
- Viral-associated cancers and disorders
- Mitochondrial Function and Pathology
- Calcium signaling and nucleotide metabolism
- Immune Response and Inflammation
- Hematopoietic Stem Cell Transplantation
- Genetic Neurodegenerative Diseases
- Coenzyme Q10 studies and effects
- Immunotherapy and Immune Responses
- Tuberculosis Research and Epidemiology
- Lymphoma Diagnosis and Treatment
University of Birmingham
2012-2020
University of Glasgow
2008-2018
MRC University of Glasgow Centre for Virus Research
2011
Institute of Cancer Research
2011
Baylor College of Medicine
2000
Myotonic dystrophy (DM; OMIM 160900, also known as dystrophia myotonica, myotonia atrophica and Steinert disease) is an autosomal dominant myotonic myopathy associated with abnormalities of other organs, including eyes, heart, endocrine system, central peripheral nervous systems, gastrointestinal bone, skin.1 The mutation underlying DM expansion unstable cytosine-thymine-guanine (CTG) trinucleotide repeat in the 3' untranslated region protein kinase (DMPK) gene chromosome 19q13.3.2-4 In...
ABSTRACT Streptococcus pneumoniae is a human commensal and pathogen able to cause variety of diseases that annually result in over million deaths worldwide. The S. Spain23F sequence type 81 lineage was among the first recognized pandemic clones responsible for almost 40% penicillin-resistant pneumococcal infections United States late 1990s. Analysis chromosome representative strain, comparison with other available genomes, indicates roles integrative conjugative elements evolution...
Thrombosis is a common, life-threatening consequence of systemic infection; however, the underlying mechanisms that drive formation infection-associated thrombi are poorly understood. Here, using mouse model Salmonella Typhimurium infection, we determined inflammation in tissues triggers thrombosis within vessels via ligation C-type lectin-like receptor-2 (CLEC-2) on platelets by podoplanin exposed to vasculature following breaching vessel wall. During mice developed persisted for weeks...
Streptococcus pneumoniae of serotype 3 possess a mucoid capsule and cause disease associated with high mortality rates relative to other pneumococci. Phylogenetic analysis complete reference genome 81 draft sequences from clonal complex 180, the predominant clone in much world, found most sampled isolates belonged clade affected by few diversifying recombinations. However, indicate significant genetic variation has accumulated over complex's entire history. Two closely related genomes, one...
ABSTRACT Intracellular killing of Streptococcus pneumoniae is complemented by induction macrophage apoptosis. Here, we show that the toxin pneumolysin (PLY) contributes both to lysosomal/phagolysosomal membrane permeabilization (LMP), an upstream event programing susceptibility apoptosis, and apoptosis execution via a mitochondrial pathway, through distinct mechanisms. PLY necessary but not sufficient for maximal LMP PLY’s ability induce independent its form cytolytic pores requires only...
Streptococcus pneumoniae is a major cause of pneumonia, sepsis and meningitis. The pore-forming toxin pneumolysin key virulence factor S. pneumoniae, which can be sensed by the NLRP3 inflammasome. Among over 90 serotypes, serotype 1 pneumococci (particularly MLST306) have emerged across globe as invasive disease. for its particularity is, however, incompletely understood. We therefore examined pneumococcal infection in human cells lung organ culture system mimicking lower respiratory tract....
The initial event in disease caused by S. pneumoniae is adhesion of the bacterium to respiratory epithelial cells, mediated surface expressed molecules including cell-wall proteins. NADH oxidase (NOX), which reduces free oxygen water cytoplasm, was identified a non-lectin enriched pneumococcal fraction. Recombinant NOX (rNOX) screened with sera obtained longitudinally from children and demonstrated age-dependent immunogenicity. ablation significantly reduced bacterial A549 cells vitro their...
Monocytes and T-cells are critical to the host response acute bacterial infection but monocytes primarily viewed as amplifying inflammatory signal. The mechanisms of cell death regulating T-cell numbers at sites incompletely characterized. in cultures peripheral blood mononuclear cells (PBMC) showed 'classic' features apoptosis following exposure pneumococci. Conversely, purified CD3+ cultured with pneumococci demonstrated necrosis membrane permeabilization. was not inhibited by necrostatin,...
The Sinorhizobium meliloti BacA ABC transporter protein plays an important role in its nodulating symbiosis with the legume alfalfa (Medicago sativa). Mycobacterium tuberculosis homolog was found to be for maintenance of chronic murine infections, yet vivo function is unknown. In plant as well mammalian host, bacteria encounter host antimicrobial peptides (AMPs). We that M. able partially complement symbiotic defect S. BacA-deficient mutant on plants and protect this vitro from activity a...
In Streptococcus pneumonia, phosphoenolpyruvate protein phosphotransferase (PtsA) is an intracellular of the monosaccharide systems. Biochemical and immunostaining methods were applied to show that PtsA also localizes bacterial cell-wall. Thus, it was suspected has functions other than its main cytoplasmic enzymatic role. Indeed, recombinant anti-rPtsA antiserum shown inhibit adhesion S. pneumoniae cultured human lung adenocarcinoma A549 cells. Screening a combinatorial peptide library...
The opportunistic pathogen Streptococcus pneumoniae has dual lifestyles: one of an asymptomatic colonizer in the human nasopharynx and other a deadly invading sterile host compartments. latter triggers overwhelming inflammatory response, partly driven via pore forming activity cholesterol dependent cytolysin (CDC), pneumolysin. Although pneumolysin-induced inflammation drives person-to-person transmission from nasopharynx, primary reservoir for pneumococcus, it also contributes to high...
The pneumococcal serine threonine protein kinase (StkP) acts as a global regulator in the pneumococcus. Bacterial mutants deficient StkP are less virulent animal models of infection. gene for this is located adjacent to its cognate phosphatase genome. dephosphorylates proteins phosphorylated by and has been shown regulate number key virulence factors modulate adherence eukaryotic cells. role pneumococci human cells not previously reported. In study we show represses pilus, factor known be...
The generation of immune cells from BM precursors is a carefully regulated process. This essential to limit the potential for oncogenesis and autoimmunity yet protect against infection. How infection modulates this unclear. Salmonella can colonize systemic sites including spleen. resolving has multiple IFN-γ-mediated acute chronic effects on progenitors, during first week IFN-γ produced by myeloid, NK, NKT, CD4(+) T cells, some lineage-negative cells. After infection, phenotype progenitors...
Streptococcus pneumoniae (S. pneumoniae), otherwise known as 'the pneumococcus', is a fascinating microbe that continues to pose significant problem public health. Currently there are no specific National Institute for Clinical Excellence (NICE) or British Thoracic Society (BTS) clinical guidelines referring the treatment of invasive pneumococcal infection. NICE suggest use lytic β-lactam antibiotic regimens management community-acquired pneumonia and bacterial meningitis; infections which...
Abstract Background: A novel retrovirus, xenotropic murine leukemia virus-related virus (XMRV), has been detected in prostate cancer samples and peripheral blood mononuclear cells (PBMC) from patients with chronic fatigue syndrome. In addition, the identified PBMCs healthy controls. These data suggest that XMRV is circulating human population. closely related to viruses, which cause lymphoid malignancies mice. The aim of this study was determine whether directly associated common forms...
Pneumococcal flavin reductase (FlaR) is known to be cell-wall associated and possess age dependent antigenicity in children. This study aimed at characterizing FlaR elucidating its involvement pneumococcal physiology virulence. Bioinformatic analysis of sequence identified three-conserved cysteine residues, suggesting a transition metal-binding capacity. Recombinant (rFlaR) bound Fe2+ exhibited FAD-dependent NADP-reductase activity, which increased the presence or excess inhibited by...
The initial event in disease caused by S. pneumoniae is adhesion of the bacterium to respiratory epithelial cells, mediated surface expressed molecules including cell-wall proteins.NADH oxidase (NOX), which reduces free oxygen water cytoplasm, was identified a non-lectin enriched pneumococcal fraction.Recombinant NOX (rNOX) screened with sera obtained longitudinally from children and demonstrated age-dependent immunogenicity.NOX ablation significantly reduced bacterial A549 cells vitro their...
Bioluminescence has been harnessed for use in bacterial reporter systems and vivo imaging of infection animal models. Strain Xen35, a bioluminescent derivative Streptococcus pneumoniae serotype 4 strain TIGR4 was previously constructed infections We have shown that Xen35 is less virulent than its parent this associated with the expression genes bioluminescence. The luxA-E pneumococcus reduces virulence down regulates pneumococcal pilus.
ABSTRACT The opportunistic pathogen Streptococcus pneumoniae has dual lifestyles: one of an asymptomatic colonizer in the human nasopharynx and other a deadly invading sterile host compartments. latter triggers overwhelming inflammatory response, partly driven via pore forming activity cholesterol dependent cytolysin (CDC), pneumolysin. Although pneumolysin-induced inflammation drives person-to-person transmission from nasopharynx, primary reservoir for pneumococcus, it also contributes to...