11 results on '"Robins‐Browne, Roy"'
Search Results
2. Phasevarion Mediated Epigenetic Gene Regulation in Helicobacter pylori.
- Author
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Srikhanta, Yogitha N., Gorrell, Rebecca J., Steen, Jason A., Gawthorne, Jayde A., Kwok, Terry, Grimmond, Sean M., Robins-Browne, Roy M., and Jennings, Michael P.
- Subjects
PATHOGENIC microorganisms ,HELICOBACTER pylori ,METHYLTRANSFERASES ,GENETIC regulation ,HAEMOPHILUS influenzae - Abstract
Many host-adapted bacterial pathogens contain DNA methyltransferases (mod genes) that are subject to phase-variable expression (high-frequency reversible ON/OFF switching of gene expression). In Haemophilus influenzae and pathogenic Neisseria, the random switching of the modA gene, associated with a phase-variable type III restriction modification (R-M) system, controls expression of a phase-variable regulon of genes (a "phasevarion"), via differential methylation of the genome in the modA ON and OFF states. Phase-variable type III R-M systems are also found in Helicobacter pylori, suggesting that phasevarions may also exist in this key human pathogen. Phylogenetic studies on the phase-variable type III modH gene revealed that there are 17 distinct alleles in H. pylori, which differ only in their DNA recognition domain. One of the most commonly found alleles was modH5 (16% of isolates). Microarray analysis comparing the wild-type P12modH5 ON strain to a P12ΔmodH5 mutant revealed that six genes were either up- or down-regulated, and some were virulenceassociated. These included flaA, which encodes a flagella protein important in motility and hopG, an outer membrane protein essential for colonization and associated with gastric cancer. This study provides the first evidence of this epigenetic mechanism of gene expression in H. pylori. Characterisation of H. pylori modH phasevarions to define stable immunological targets will be essential for vaccine development and may also contribute to understanding H. pylori pathogenesis. [ABSTRACT FROM AUTHOR]
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- 2011
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3. The Type III Effectors NleE and NleB from Enteropathogenic E. coli and OspZ from Shigella Block Nuclear Translocation of NF-ĸB p65.
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Newton, Hayley J., Pearson, Jaclyn S., Badea, Luminita, Kelly, Michelle, Lucas, Mark, Holloway, Gavan, Wagstaff, Kylie M., Dunstone, Michelle A., Sloan, Joan, Whisstock, James C., Kaper, James B., Robins-Browne, Roy M., Jans, David A., Frankel, Gad, Phillips, Alan D., Coulson, Barbara S., and Hartland, Elizabeth L.
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PATHOGENIC microorganisms ,SECRETION ,PROTEINS ,ESCHERICHIA coli ,SHIGELLA ,CELL nuclei - Abstract
Many bacterial pathogens utilize a type III secretion system to deliver multiple effector proteins into host cells. Here we found that the type III effectors, NleE from enteropathogenic E. coli (EPEC) and OspZ from Shigella, blocked translocation of the p65 subunit of the transcription factor, NF-κB, to the host cell nucleus. NF-κB inhibition by NleE was associated with decreased IL-8 expression in EPEC-infected intestinal epithelial cells. Ectopically expressed NleE also blocked nuclear translocation of p65 and c-Rel, but not p50 or STAT1/2. NleE homologues from other attaching and effacing pathogens as well OspZ from Shigella flexneri 6 and Shigella boydii, also inhibited NF-κB activation and p65 nuclear import; however, a truncated form of OspZ from S. flexneri 2a that carries a 36 amino acid deletion at the C-terminus had no inhibitory activity. We determined that the C-termini of NleE and full length OspZ were functionally interchangeable and identified a six amino acid motif, IDSY(M/I)K, that was important for both NleE- and OspZ-mediated inhibition of NF-κB activity. We also established that NleB, encoded directly upstream from NleE, suppressed NF-κB activation. Whereas NleE inhibited both TNFa and IL-1β stimulated p65 nuclear translocation and IkB degradation, NleB inhibited the TNFa pathway only. Neither NleE nor NleB inhibited AP-1 activation, suggesting that the modulatory activity of the effectors was specific for NF-κB signaling. Overall our data show that EPEC and Shigella have evolved similar T3SS-dependent means to manipulate host inflammatory pathways by interfering with the activation of selected host transcriptional regulators. [ABSTRACT FROM AUTHOR]
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- 2010
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4. Shiga Toxin-producing Escherichia coli Strains Negative for Locus of Enterocyte Effacement.
- Author
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Newton, Hayley J., Sloan, Joan, Bulach, Dieter M., Seemann, Torsten, Allison, Cody C., Tauschek, Marija, Robins-Browne, Roy M., Paton, James C., Whittam, Thomas S., Paton, Adrienne W., and Hartland, Elizabeth L.
- Subjects
ESCHERICHIA coli diseases ,HEMOLYTIC-uremic syndrome ,PATHOGENIC microorganisms ,MICROBIAL virulence ,NUCLEOTIDE sequence ,GENES - Abstract
Most Shiga toxin-producing Escherichia coli (STEC) infections that are associated with severe sequelae such as hemolytic uremic syndrome (HUS) are caused by attaching and effacing pathogens that carry the locus of enterocyte effacement (LEE). However, a proportion of STEC isolates that do not carry LEE have been associated with HUS. To clarify the emergence of LEE-negative STEC, we compared the genetic composition of the virulence plasmids pO113 and pO157 from LEE-negative and LEE-positive STEC, respectively. The complete nucleotide sequence of pO113 showed that several plasmid genes were shared by STEC O157:H7. In addition, allelic profi ling of the ehxA gene demonstrated that pO113 belongs to a different evolutionary lineage than pO157 and that the virulence plasmids of LEE-negative STEC strains were highly related. In contrast, multilocus sequence typing of 17 LEE-negative STEC isolates showed several clonal groups, suggesting that pathogenic LEE-negative STEC has emerged several times throughout its evolution. [ABSTRACT FROM AUTHOR]
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- 2009
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5. Atypical Enteropathogenic Escherichia coli Infection and Prolonged Diarrhea in Children.
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Nguyen, Rang N., Taylor, Louise S., Tauschek, Marija, and Robins-Browne, Roy M.
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ESCHERICHIA coli ,DIARRHEA ,ADENOVIRUSES ,ROTAVIRUSES ,PATHOGENIC microorganisms - Abstract
Some clinical isolates of enteropathogenic Escherichia coli (EPEC) lack bundle-forming pili and are termed atypical EPEC. The aim of this study was to determine if atypical EPEC are pathogens by comparing the clinical features of patients infected with atypical EPEC with those of children infected with other causative agents of diarrhea. Fecal samples obtained from children attending the Royal Children's Hospital in Melbourne for investigation of diarrhea were examined for adenovirus, rotavirus, Campylobacter spp., Salmonella spp., protozoa, and pathogenic E. coli. Clinical data were obtained by using a standardized pro forma and analyzed separately. Patients infected with atypical EPEC experienced mild, nondehydrating, and noninflammatory diarrhea that was not particularly associated with fever, vomiting, or abdominal pain. However, the duration of diarrhea in patients infected with atypical EPEC was significantly longer than that caused by the other species or where no pathogens were identified. Infection with atypical EPEC is associated with prolonged diarrhea. [ABSTRACT FROM AUTHOR]
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- 2006
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6. The Relentless Evolution of Pathogenic Escherichia coli.
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Robins-Browne, Roy M.
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ESCHERICHIA coli , *TOXINS , *INTESTINAL diseases , *PATHOGENIC microorganisms , *FUNGUS-bacterium relationships , *ENTEROBACTERIACEAE - Abstract
The article cites a research study on the relentless evolution of pathogenic escherichia coli. Shiga toxin producing strains of Escherichia coli are important emerging pathogens. Unknown before the late 1970s, these bacteria are now recognized as a leading cause of sporadic cases and outbreaks of afebrile bloody diarrhea in industrialized countries and are the major cause of diarrhea- associated hemolytic uremic syndrome (HUS) worldwide. The damage these toxins inflict on these cells triggers intravascular coagulation, which leads to the major manifestations of HUS.
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- 2005
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7. Factors That Explain Excretion of Enteric Pathogens by Persons Without Diarrhea.
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Levine, Myron M. and Robins-Browne, Roy M.
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EXCRETION , *INTESTINAL infections , *PATHOGENIC microorganisms , *ETIOLOGY of diseases , *DIARRHEA , *FECAL analysis - Abstract
Excretion of enteropathogens by subjects without diarrhea influences our appreciation of the role of these pathogens as etiologic agents. Characteristics of the pathogens and host and environmental factors help explain asymptomatic excretion of diarrheal pathogens by persons without diarrhea. After causing acute diarrhea followed by clinical recovery, some enteropathogens are excreted asymptomatically for many weeks. Thus, in a prevalence survey of persons without diarrhea, some may be excreting pathogens from diarrheal episodes experienced many weeks earlier. Volunteer challenges with Vibrio cholerae O1, enterotoxigenic Escherichia coli (ETEC), enteropathogenic E. coli, Campylobacter jejuni, and Giardia lamblia document heterogeneity among enteropathogen strains, with some inexplicably not eliciting diarrhea. The immune host may not manifest diarrhea following ingestion of a pathogen but may nevertheless asymptomatically excrete. Some human genotypes render them less susceptible to symptomatic or severe diarrheal infection with certain pathogens such as Vibrio cholerae O1 and norovirus. Pathogens in stools of individuals without diarrhea may reflect recent ingestion of inocula too small to cause disease in otherwise susceptible hosts or of animal pathogens (eg, bovine or porcine ETEC) that do not cause human illness. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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8. Laboratory Diagnostic Challenges in Case/Control Studies of Diarrhea in Developing Countries.
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Robins-Browne, Roy M. and Levine, Myron M.
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CASE-control method , *DIAGNOSIS of diarrhea , *CLINICAL pathology , *DIAGNOSTIC microbiology , *PATHOGENIC microorganisms , *FECAL analysis ,DEVELOPING countries - Abstract
Case/control studies of acute infectious diarrhea require accurate and dependable laboratory tests to detect pathogens in samples from both symptomatic patients and healthy control subjects. The methods used to detect these pathogens have usually been evaluated on patient samples only, and their performance on samples from control subjects is mostly unknown. Because many pathogens occur at a high overall frequency in developing countries and thus may be present in a notable proportion of control subjects as well as patients, the relative ability of a diagnostic test to detect these pathogens in diarrheic and normal stools can have a profound effect on the interpretation of case/control data. [ABSTRACT FROM AUTHOR]
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- 2012
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9. Nasopharyngeal microbial interactions in the era of pneumococcal conjugate vaccination.
- Author
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Dunne, Eileen M., Smith-Vaughan, Heidi C., Robins-Browne, Roy M., Mulholland, E. Kim, and Satzke, Catherine
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NASOPHARYNX diseases , *PNEUMOCOCCAL vaccines , *PATHOGENIC microorganisms , *COLONIZATION , *ETIOLOGY of diseases , *VACCINATION of children - Abstract
Highlights: [•] Clinically important pathogens often colonise the nasopharynx of children. [•] Vaccination may alter colonisation dynamics and impact disease aetiology. [•] We review co-colonisation of pathogens and the impact of pneumococcal vaccination. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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10. Chips with everything: DNA microarrays in infectious diseases
- Author
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Bryant, Penelope A, Venter, Deon, Robins-Browne, Roy, and Curtis, Nigel
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COMMUNICABLE diseases , *HUMAN genome , *DNA microarrays , *PATHOGENIC microorganisms , *IMMOBILIZED nucleic acids , *BIOCHIPS - Abstract
Two developments are set to revolutionise research in and clinical management of infectious diseases. First, the completion of the human genome project together with the sequencing of many pathogen genomes, and second, the development of microarray technology. This review explains the principles underlying DNA microarrays and highlights the uses to which they are being put to investigate the molecular basis of infectious diseases. Pathogen studies enable identification of both known and novel organisms, understanding of genetic evolution, and investigation of determinants of pathogenicity. Host studies show the complexities of development and activation of both innate and adaptive immunity. Host-pathogen studies allow global analysis of gene expression during pathogenesis. Microarray technology will accelerate our understanding of the complex genetic processes underlying the interaction between microorganisms and the host, with consequent improvements in the diagnosis, treatment, and prevention of infectious diseases. [Copyright &y& Elsevier]
- Published
- 2004
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11. Rabbit-specific fimbriae, Ral, alter the patterns of in vitro adherence and intestinal colonisation of rabbits by human-specific enteropathogenic E. coli
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Hart, Emily, Tauschek, Marija, Bennett-Wood, Vicki, Hartland, Elizabeth L., and Robins-Browne, Roy M.
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PILI (Microbiology) , *LABORATORY rabbits , *PATHOGENIC microorganisms , *ESCHERICHIA coli , *DIARRHEA in children , *INFANT mortality , *CELL membranes ,DEVELOPING countries - Abstract
Abstract: Enteropathogenic Escherichia coli (EPEC) poses a significant threat to human health, causing diarrhoea in children worldwide, and is a leading cause of infant mortality in developing countries. The pathogenic effects of EPEC and other attaching-effacing (A/E) bacteria result from adhesion to the intestinal mucosa by a variety of mechanisms, including fimbrial adhesins, which are believed to contribute to the host and tissue specificity of EPEC by their interaction with specific receptors on cell surfaces. In this study we investigated the contribution of a fimbrial adhesin, Ral, of rabbit-specific EPEC (REPEC) to host specificity by introducing Ral into derivatives of human-specific EPEC (hEPEC) strain, E2348/69, in which expression of the fimbrial adhesin, Bfp, had been interrupted. Although unable to cause diarrhoeal disease in rabbits, Ral-bearing hEPEC strains colonised rabbit intestine more efficiently and showed altered intestinal localisation when compared to an isogenic Ral-negative strain. These findings suggest that Ral enhances the initial interaction between a ΔbfpA mutant of hEPEC and rabbit intestine and may influence tissue specificity, but is not sufficient on its own to transform hEPEC into a rabbit pathogen. This study affords new insights into the complex mechanisms which determine the host range of bacterial pathogens. [Copyright &y& Elsevier]
- Published
- 2009
- Full Text
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