Molecular investigation of an epidemic MRSA: A comparative study of its recognition, introduction and spread in the west of Scotland

The incidence of infections caused by methicillin-resistant Staphylococcus aureus (MRSA) has increased world-wide over the past 30 years. A strain that was introduced into Scotland in 1990 via a patient recently returned from Lisbon, Portugal had an unusually resistant phenotype. Ninety- three isolates were selected and investigated by molecular methods. The principal method chosen was agarose gel electrophoresis following digestion of whole cell genomic DNA with the restriction enzymes HhaI and Sau3AI. These enzymes recognise 4-base DNA sequences and produced an analytical window at the top of an agarose gel, which allowed the recognition of plasmid DNA fragments and partial digest products. The final result of electrophoresis by this method was a considerable improvement over previous methods employing enzymes that are 6-base cutters. The strain was studied in parallel with control groups of Staph, aureus that consisted of methicillin-sensitive Staph, aureus, sporadic isolates of MRSA and the epidemic strains EMRSA-1, EMRSA-15 and EMRSA-16. Analysis of the HhaI restriction enzyme fragmentation patterns (REFP) of the "new" strain and control groups by Dice coefficients of similarity validated the technique with respect to discrimination; it was demonstrated that REFP's of epidemiologically um-elated MSSA isolates had low Dice coefficient values (mean So value = 66%) and that REFP's of known epidemiologically related isolates such as EMRSA-15 had high coefficients of similarity (mean SD value = 99%). The technique showed that all isolates of the new strain were clonal in origin (mean SD value = 95%) and in addition, highlighted the existence of a number of clonal variants (subtypes) to the major REFP type. Sixty-eight isolates (73%) gave a genomic fingerprint identical to the index case and were designated HhaI type H1. Twenty-five isolates were variants of this type and were designated type LH2 (7 isolates), LH3 (6 isolates), LH10 (2 isolates) and fifteen of the twenty-five were unique variants designated LH4 - LH9 and LH11 - LH14. Nine isolates of another strain, imported from France and phenotypically similar to the study strain were shown to be genetically closely related to it. Inter-group matching of REFP's showed each control group to be genetically distinct to each other and to the "new" MRSA strain. In a collaborative study, this new strain which has been trivially termed the "Lisbon strain" was shown to be closely related to the now well characterised Iberian clone MRSA. Variants detected using HhaI/Sau3AI typing also showed parallel variation in PFGE. A small number of genomic variants were also found within the EMRSA-1, 15 and 16 control groups, highlighting the capacity of the technique to detect minor genetic change. Restriction enzyme fingerprinting of whole cell genomic DNA using the restriction enzymes HhaI and Sau3AI proved to be a simple, economic and highly discriminatory method of typing Staph. aureus strains requiring no expensive apparatus

Circulating emm types of Streptococcus pyogenes in Scotland: 2011-2015

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E-Data Quality: How Publishers and Libraries are Working Together to Improve Data Quality

High quality data is essential for discovery and access of e-resources, but in many cases low quality, inaccurate information leads to low usage and a poor return on library investment dollars. In this article, publishers, aggregators, librarians, and knowledge base providers talk about how they are working together to improve access to e-resources

Developmental Regulation of an Adhesin Gene during Cellular Morphogenesis in the Fungal Pathogen Candida albicans

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Defining the pig microglial transcriptome reveals its core signature, regional heterogeneity, and similarity with human and rodent microglia:Pig microglial transcriptome signature

Microglia play key roles in brain homeostasis as well as responses to neurodegeneration and neuroinflammatory processes caused by physical disease and psychosocial stress. The pig is a physiologically relevant model species for studying human neurological disorders, many of which are associated with microglial dysfunction. Furthermore, pigs are an important agricultural species, and there is a need to understand how microglial function affects their welfare. As a basis for improved understanding to enhance biomedical and agricultural research, we sought to characterize pig microglial identity at genome-wide scale and conduct inter-species comparisons. We isolated pig hippocampal tissue and microglia from frontal cortex, hippocampus, and cerebellum, as well as alveolar macrophages from the lungs and conducted RNA-sequencing (RNAseq). By comparing the transcriptomic profiles between microglia, macrophages, and hippocampal tissue, we derived a set of 239 highly enriched genes defining the porcine core microglial signature. We found brain regional heterogeneity based on 150 genes showing significant (adjusted p < 0.01) regional variations and that cerebellar microglia were most distinct. We compared normalized gene expression for microglia from human, mice and pigs using microglia signature gene lists derived from each species and demonstrated that a core microglial marker gene signature is conserved across species, but that species-specific expression subsets also exist. Our data provide a valuable resource defining the pig microglial transcriptome signature that validates and highlights pigs as a useful large animal species bridging between rodents and humans in which to study the role of microglia during homeostasis and disease

The environmental stress sensitivities of pathogenic Candida species, including Candida auris, and implications for their spread in the hospital setting

We are grateful to Dr. David Stead, Evelyn Argo and Craig Pattison (Aberdeen Proteomics Core Facility) for their expert identification of Candida isolates by MALDI ToF MS, and to Dr Jill King and our colleagues in the Aberdeen Fungal Group for their helpful advice. AJPB and NARG were supported by a programme grant from the Medical Research Council [www.mrc.ac.uk] (grant number MR/M026663/1) and by the Medical Research Council Centre for Medical Mycology and the University of Aberdeen (grant number MR/N006364/1). AJPB was also supported by the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk] (grant numbers BB/F00513X/1, BB/P020119/1), and AWW by the Scottish Government’s Rural and Environment Science and Analytical Services (RESAS) division. NARG was also supported by grants from the Wellcome Trust [www.wellcome.ac.uk] (grant numbers 075470, 086827, 093378, 097377, 099197, 101873, 102705, 200208). DMM was supported by National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [www.nc3rs.org.uk] (grant numbers NC/S001557/1 and NC/N002482/1) and the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk] (grant number BB/P02050X/1). HH was supported by the John Duthie Scholarship from the University of Aberdeen’s Development Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Little evidence for association between the TGFBR1*6A variant and colorectal cancer: a family-based association study on non-syndromic family members from Australia and Spain

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Genome-wide linkage studies have identified the 9q22 chromosomal region as linked with colorectal cancer (CRC) predisposition. A candidate gene in this region is transforming growth factor β receptor 1 (TGFBR1). Investigation of TGFBR1 has focused on the common genetic variant rs11466445, a short exonic deletion of nine base pairs which results in truncation of a stretch of nine alanine residues to six alanine residues in the gene product. While the six alanine (*6A) allele has been reported to be associated with increased risk of CRC in some population based study groups this association remains the subject of robust debate. To date, reports have been limited to population-based case–control association studies, or case–control studies of CRC families selecting one affected individual per family. No study has yet taken advantage of all the genetic information provided by multiplex CRC families

Impact of changes at the Candida albicans cell surface upon immunogenicity and colonisation in the gastrointestinal tract

Acknowledgements This work was supported by a programme grant from the UK Medical Research Council (MR/M026663/1; MR/M026663/2) and by the Medical Research Council Centre for Medical Mycology (MR/N006364/1; MR/N006364/2). NARG acknowledges Wellcome support for a Senior Investigator (101873/Z/13/Z), Collaborative (200208/A/15/Z; 215599/Z/19/Z) and Strategic Awards (097377/Z11/Z). LR, SHD and AWW received core funding support from the Scottish Government’s Rural and Environment Science and Analytical Services (RESAS) division. MGN was supported by an ERC Advanced Grant (833247) and a Spinoza Grant of the Netherlands Organization for Scientific Research.Peer reviewedPublisher PD

Accessing bacterial dark matter for improved enzyme discovery and engineering

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Cellular responses of Candida albicans to phagocytosis and the extracellular activities of neutrophils are critical to counteract carbohydrate starvation, oxidative and nitrosative stress

Acknowledgments We thank Alexander Johnson (yhb1D/D), Karl Kuchler (sodD/D mutants), Janet Quinn (hog1D/D, hog1/cap1D/D, trx1D/D) and Peter Staib (ssu1D/D) for providing mutant strains. We acknowledge helpful discussions with our colleagues from the Microbial Pathogenicity Mechanisms Department, Fungal Septomics and the Microbial Biochemistry and Physiology Research Group at the Hans Kno¨ll Institute (HKI), specially Ilse D. Jacobsen, Duncan Wilson, Sascha Brunke, Lydia Kasper, Franziska Gerwien, Sea´na Duggan, Katrin Haupt, Kerstin Hu¨nniger, and Matthias Brock, as well as from our partners in the FINSysB Network. Author Contributions Conceived and designed the experiments: PM HW IMB AJPB OK BH. Performed the experiments: PM CD HW. Analyzed the data: PM HW IMB AJPB OK BH. Wrote the paper: PM HW OK AJPB BH.Peer reviewedPublisher PD