Alan R Brown

University of Exeter | UoE · Department of Biosciences

The genotyping of pathogens within cystic fibrosis cohorts is an important process, enabling the detection of transmissible and clinically-important strains. Traditionally this has been via culture-dependent processes. However, culture-independent investigation of respiratory samples is becoming more common, with such approaches highlighting the li...

While Pseudomonas aeruginosa (PA) cross-infection is well documented among patients with cystic fibrosis (CF), the equivalent risk among patients with non-CF bronchiectasis (NCFB) is unclear, particularly those managed alongside patients with CF. We performed analysis of PA within a single centre that manages an unsegregated NCFB cohort alongside a...

Sphingolipids (SLs) are ubiquitous elements in eukaryotic membranes and are also found in some bacterial and viral species. As well as playing an integral structural role, SLs also act as potent signalling molecules involved in numerous cellular pathways and have been linked to many human diseases. A central SL signalling molecule is sphingosine-1-...

Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, plays a critical role in the orchestration of immune responses. S1P levels within the mammalian host are tightly regulated, in part through the activity of S1P lyase (S1PL) which catalyses its irreversible degradation. Herein we describe the identification and characterization of s...

Introduction and objectives Pseudomonas aeruginosa (Pa) is a significant respiratory pathogen. Research in Cystic Fibrosis cohorts has revealed transmissible strains, leading to heightened infection control protocols due to concerns of cross-infection. In patients with Non-Cystic Fibrosis Bronchiectasis (NCFB), the research is more limited. Our obj...

Objectives We aimed to define the phenotypic and genotypic adaptations that occur in the Burkholderia cepacia complex (BCC) during chronic infection of the cystic fibrosis (CF) lung. Methods We studied a total of 57 BCC isolates from 15 CF patients (2–6 isolates per patient), spanning infection periods ranging from 3 to 14 years. We assessed virul...

In common with other members of the Burkholderia cepacia complex (BCC), Burkholderia multivorans is capable of producing exopolysaccharide (EPS) when grown on certain mannitol-rich media. The significance of the resulting mucoid phenotype and the genome-wide response to mannitol has never been characterized despite its clinical relevance following...

Burkholderia multivorans, a member of the Burkholderia cepacia complex (Bcc), is an important pathogen of the cystic fibrosis (CF) lung. Mannitol, approved as an inhaled osmolyte therapy for use in CF patients, promotes exopolysaccharide (EPS) production by the Bcc. In the present study, we investigated the role of mannitol-induced EPS in the adher...

Peroxiredoxins are ubiquitous proteins that catalyze the reduction of hydroperoxides, thus conferring resistance to oxidative stress. Using high-resolution mass spectrometry, we recently reclassified one such peroxiredoxin, bacterioferritin comigratory protein (BCP) of Escherichia coli, as an atypical 2-Cys peroxiredoxin that functions through the...

Bacterioferritin comigratory protein (BCP) is a bacterial thioredoxin-dependent thiol peroxidase that reduces a variety of peroxide substrates. Using high-resolution Fourier transform ion cyclotron resonance mass spectrometry coupled with top-down fragmentation techniques, we have analyzed the mechanistic details of hydrogen peroxide reduction by E...

The species that presently constitute the Burkholderia cepacia complex (Bcc) have multiple roles; they include soil and water saprophytes, bioremediators, and plant, animal and human pathogens. Since the first description of pathogenicity in the Bcc was based on sour skin rot of onion bulbs, this study returned to this plant host to investigate the...

We previously reported reduced expression of erythroid-associated factor (ERAF) within haematopoietic tissues of rodent scrapie models, suggesting an unrecognized role for the erythroid lineage in prion disease. In the present study, we compared the expression of a panel of erythroid genes within four murine scrapie models and five virus infection...

The morbidity and mortality of patients with cystic fibrosis (CF) is primarily determined by chronic and debilitating lung infections caused by a surprisingly narrow spectrum of bacterial pathogens. Pseudomonas aeruginosa is by far the most prevalent life-threatening CF pathogen. In the absence of aggressive early therapy, it infects the majority o...

Several species within the Burkholderia cepacia complex (BCC) have emerged as significant opportunistic pathogens of patients with cystic fibrosis (CF). BCC infection is typically associated with a poor clinical prognosis and decreased survival. These factors, combined with the existence of highly transmissible epidemic strains, have resulted in st...

Using a conditional mutagenesis strategy we demonstrate here that a gene cluster encoding putative aminoarabinose (Ara4N) biosynthesis enzymes is essential for the viability of Burkholderia cenocepacia. Loss of viability is associated with dramatic changes in bacterial cell morphology and ultrastructure, increased permeability to propidium iodide,...

The molecular events that underlie prion disease neuropathology remain poorly defined. Within the hippocampus of the ME7/CV mouse scrapie model, profound CA1 neuronal loss occurs between 160 and 180 days post-infection (dpi). To elucidate the molecular events that may contribute to this neuronal loss, we have applied Affymetrix high-density oligonu...

The major neuropathological features of the transmissible spongiform encephalopathies (TSEs) are well documented, however, the underlying molecular events are poorly defined. We have applied cDNA expression arrays and quantitative RT-PCR to the study of gene expression in the brain, and more specifically in the hippocampus, of the well-characterize...

The temporal course of cerebral cytokine gene expression was investigated in the ME7/CV murine scrapie model to determine any association with neuropathological events. Analysis by RNase protection assay (RPA) demonstrated no transcripts for ILs 2, 3, 4, 5, 6, 7, 10, 12p40 and 13, granulocyte macrophage colony-stimulating factor, IFN-gamma or lymph...

The temporal course of cerebral cytokine gene expression was investigated in the ME7/CV murine scrapie model to determine any association with neuropathological events. Analysis by RNase protection assay (RPA) demonstrated no transcripts for ILs 2, 3, 4, 5, 6, 7, 10, 12p40 and 13, granulocyte macrophage colony-stimulating factor, IFN-γ or lymphotox...

The Tn1546-related elements of 48 Van glycopetide-resistant enterococci were compared. Ten distinct Tn1546 types were identified with variation primarily due to IS1542 and IS1216V-like insertions. Clonal isolates frequently differed in their Tn1546 type, indicating instability of Tn1546-related elements. A putative hybrid promoter was identified, g...

In February 1996, a Hospital Infection Control Practices Advisory Committee-style screening program was commenced to isolate and subsequently characterize glycopeptide-resistant enterococci (GRE) from patients at a hospital trust in Glasgow, Scotland. Over the next 30 months, GRE were isolated from 154 patients. GRE were isolated from patients in t...

This study reports an outbreak of infection and colonization caused by vancomycin-resistant enterococci (VRE) in the renal service of a large teaching hospital. The polymerase chain reaction and pulsed-field gel electrophoresis were used to study the epidemiology of 26/34 strains of vancomycin-resistant Enterococcus faecalis and Enterococcus faeciu...