Bacteriology at #UniBirmingham
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Bacteriology at #UniBirmingham
Bacteriology at the University of Birmingham
Curated by Mark Pallen
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PLoS ONE: Calculating Orthologs in Bacteria and Archaea: A Divide and Conquer Approach

PLoS ONE: Calculating Orthologs in Bacteria and Archaea: A Divide and Conquer Approach | Bacteriology at #UniBirmingham | Scoop.it

Among proteins, orthologs are defined as those that are derived by vertical descent from a single progenitor in the last common ancestor of their host organisms. Our goal is to compute a complete set of protein orthologs derived from all currently available complete bacterial and archaeal genomes. Traditional approaches typically rely on all-against-all BLAST searching which is prohibitively expensive in terms of hardware requirements or computational time (requiring an estimated 18 months or more on a typical server). Here, we present xBASE-Orth, a system for ongoing ortholog annotation, which applies a “divide and conquer” approach and adopts a pragmatic scheme that trades accuracy for speed. Starting at species level, xBASE-Orth carefully constructs and uses pan-genomes as proxies for the full collections of coding sequences at each level as it progressively climbs the taxonomic tree using the previously computed data. This leads to a significant decrease in the number of alignments that need to be performed, which translates into faster computation, making ortholog computation possible on a global scale. Using xBASE-Orth, we analyzed an NCBI collection of 1,288 bacterial and 94 archaeal complete genomes with more than 4 million coding sequences in 5 weeks and predicted more than 700 million ortholog pairs, clustered in 175,531 orthologous groups. We have also identified sets of highly conserved bacterial and archaeal orthologs and in so doing have highlighted anomalies in genome annotation and in the proposed composition of the minimal bacterial genome. In summary, our approach allows for scalable and efficient computation of the bacterial and archaeal ortholog annotations. In addition, due to its hierarchical nature, it is suitable for incorporating novel complete genomes and alternative genome annotations. The computed ortholog data and a continuously evolving set of applications based on it are integrated in the xBASE database, available at http://www.xbase.ac.uk/.

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Bio303 Module Applied & Environmental Microbiology

Bio303 Module Applied & Environmental Microbiology | Bacteriology at #UniBirmingham | Scoop.it

Pallen's lectures on Global Health and Diagnostic Microbiology

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SadA, a trimeric autotransporter from Salmonella enterica serovar Typhimurium, can promote biofilm formation and provides limited protection against infection. -- Raghunathan et al., 10.1128/IAI.05...

SadA, a trimeric autotransporter from Salmonella enterica serovar Typhimurium, can promote biofilm formation and provides limited protection against infection. -- Raghunathan et al., 10.1128/IAI.05... | Bacteriology at #UniBirmingham | Scoop.it

Salmonella enterica is a major cause of morbidity worldwide and mortality in children and immunocompromised individuals in sub-Saharan Africa. Outer membrane proteins of Salmonella are of significance because they are at the interface between the pathogen and the host, they can contribute to adherence, colonization and virulence and are frequently targets of antibody-mediated immunity. In this study the properties of SadA, a purported trimeric autotransporter adhesin of Salmonella enterica serovar Typhimurium, was examined. We demonstrated that SadA is exposed on the Salmonella cell surface in vitro and in vivo during infection of mice. Expression of SadA resulted in cell aggregation, biofilm formation and increased adhesion to human intestinal Caco-2 epithelial cells. Immunisation of mice with folded, full-length, purified SadA elicited an IgG response which provided limited protection against bacterial challenge. When anti-SadA IgG titres were enhanced by administering alum-precipitated protein a modest additional protection was afforded. Therefore, despite SadA having pleiotropic functions it is not a dominant, protective antigen for antibody-mediated protection against Salmonella.

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The Birmingham Fellowships - Research opportunities at The University of Birmingham

Over the next 18 months the University of Birmingham is starting a global search for rising star researchers with an eye on employing up to 50 Birmingham Fel...
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A genomic storm in critically injured humans. [J Exp Med. 2011] - PubMed - NCBI

Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and burn injury, as well as in healthy subjects receiving low-dose bacterial endotoxin, and show that these severe stresses produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected "genomic storm." In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously increased expression of genes involved in the systemic inflammatory, innate immune, and compensatory antiinflammatory responses, as well as in the suppression of genes involved in adaptive immunity. Furthermore, complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hit and differ only in the magnitude and duration of this genomic reprioritization. The similarities in gene expression patterns between different injuries reveal an apparently fundamental human response to severe inflammatory stress, with genomic signatures that are surprisingly far more common than different. Based on these transcriptional data, we propose a new paradigm for the human immunological response to severe injury.

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Structure and function of BamE within the outer mem... [EMBO Rep. 2011] - PubMed - NCBI

Structure and function of BamE within the outer mem... [EMBO Rep. 2011] - PubMed - NCBI | Bacteriology at #UniBirmingham | Scoop.it

Insertion of folded proteins into the outer membrane of Gram-negative bacteria is mediated by the essential β-barrel assembly machine (Bam). Here, we report the native structure and mechanism of a core component of this complex, BamE, and show that it is exclusively monomeric in its native environment of the periplasm, but is able to adopt a distinct dimeric conformation in the cytoplasm. BamE is shown to bind specifically to phosphatidylglycerol, and comprehensive mutagenesis and interaction studies have mapped key determinants for complex binding, outer membrane integrity and cell viability, as well as revealing the role of BamE within the Bam complex.

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Open-Source Genomic Analysis of Shiga-Toxin–Producing E. coli O104:H4 — NEJM

Open-Source Genomic Analysis of Shiga-Toxin–Producing E. coli O104:H4 — NEJM | Bacteriology at #UniBirmingham | Scoop.it
Open-Source Genomic Analysis of Shiga-Toxin–Producing E. coli O104:H4
An outbreak caused by Shiga-toxin–producing Escherichia coli O104:H4 occurred in Germany in May and June of 2011, with more than 3000 persons infected. Here, we report a cluster of cases associated with a single family and describe an open-source genomic analysis of an isolate from one member of the family. This analysis involved the use of rapid, bench-top DNA sequencing technology, open-source data release, and prompt crowd-sourced analyses. In less than a week, these studies revealed that the outbreak strain belonged to an enteroaggregative E. coli lineage that had acquired genes for Shiga toxin 2 and for antibiotic resistance.
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All the tweets from ABPH11

The tweets from Applied Bioinformatics & Public Health 2011- preserved for posterity.
pathogenomenick: Started on my train journey through the bucolic scenery of middle England to Hinxton, nr.
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