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      Enhanced biofilm formation and multi‐host transmission evolve from divergent genetic backgrounds in C ampylobacter jejuni

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          Summary

          Multicellular biofilms are an ancient bacterial adaptation that offers a protective environment for survival in hostile habitats. In microaerophilic organisms such as C ampylobacter, biofilms play a key role in transmission to humans as the bacteria are exposed to atmospheric oxygen concentrations when leaving the reservoir host gut. Genetic determinants of biofilm formation differ between species, but little is known about how strains of the same species achieve the biofilm phenotype with different genetic backgrounds. Our approach combines genome‐wide association studies with traditional microbiology techniques to investigate the genetic basis of biofilm formation in 102  C ampylobacter jejuni isolates. We quantified biofilm formation among the isolates and identified hotspots of genetic variation in homologous sequences that correspond to variation in biofilm phenotypes. Thirteen genes demonstrated a statistically robust association including those involved in adhesion, motility, glycosylation, capsule production and oxidative stress. The genes associated with biofilm formation were different in the host generalist ST‐21 and ST‐45 clonal complexes, which are frequently isolated from multiple host species and clinical samples. This suggests the evolution of enhanced biofilm from different genetic backgrounds and a possible role in colonization of multiple hosts and transmission to humans.

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          The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences.

          Campylobacter jejuni, from the delta-epsilon group of proteobacteria, is a microaerophilic, Gram-negative, flagellate, spiral bacterium-properties it shares with the related gastric pathogen Helicobacter pylori. It is the leading cause of bacterial food-borne diarrhoeal disease throughout the world. In addition, infection with C. jejuni is the most frequent antecedent to a form of neuromuscular paralysis known as Guillain-Barré syndrome. Here we report the genome sequence of C. jejuni NCTC11168. C. jejuni has a circular chromosome of 1,641,481 base pairs (30.6% G+C) which is predicted to encode 1,654 proteins and 54 stable RNA species. The genome is unusual in that there are virtually no insertion sequences or phage-associated sequences and very few repeat sequences. One of the most striking findings in the genome was the presence of hypervariable sequences. These short homopolymeric runs of nucleotides were commonly found in genes encoding the biosynthesis or modification of surface structures, or in closely linked genes of unknown function. The apparently high rate of variation of these homopolymeric tracts may be important in the survival strategy of C. jejuni.
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            Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18.

            Salmonella enterica serovar Typhi (S. typhi) is the aetiological agent of typhoid fever, a serious invasive bacterial disease of humans with an annual global burden of approximately 16 million cases, leading to 600,000 fatalities. Many S. enterica serovars actively invade the mucosal surface of the intestine but are normally contained in healthy individuals by the local immune defence mechanisms. However, S. typhi has evolved the ability to spread to the deeper tissues of humans, including liver, spleen and bone marrow. Here we have sequenced the 4,809,037-base pair (bp) genome of a S. typhi (CT18) that is resistant to multiple drugs, revealing the presence of hundreds of insertions and deletions compared with the Escherichia coli genome, ranging in size from single genes to large islands. Notably, the genome sequence identifies over two hundred pseudogenes, several corresponding to genes that are known to contribute to virulence in Salmonella typhimurium. This genetic degradation may contribute to the human-restricted host range for S. typhi. CT18 harbours a 218,150-bp multiple-drug-resistance incH1 plasmid (pHCM1), and a 106,516-bp cryptic plasmid (pHCM2), which shows recent common ancestry with a virulence plasmid of Yersinia pestis.
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              Genome-wide association study of copy number variation in 16,000 cases of eight common diseases and 3,000 shared controls

              Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to play an important role in genetic susceptibility to common disease. To address this we undertook a large direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed ~19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated ~50% of all common CNVs larger than 500bp. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell-lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease, IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis, and type 1 diabetes, and TSPAN8 for type 2 diabetes, though in each case the locus had previously been identified in SNP-based studies, reflecting our observation that the majority of common CNVs which are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs which can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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                Author and article information

                Journal
                Environ Microbiol
                Environ. Microbiol
                10.1111/(ISSN)1462-2920
                EMI
                Environmental Microbiology
                John Wiley and Sons Inc. (Hoboken )
                1462-2912
                1462-2920
                November 2015
                14 October 2015
                : 17
                : 11 , Pathogen Ecology ( doiID: 10.1111/emi.2015.17.issue-11 )
                : 4779-4789
                Affiliations
                [ 1 ] College of Medicine Institute of Life ScienceSwansea University SwanseaUK
                [ 2 ] MRC CLIMB Consortium Institute of Life ScienceSwansea University SwanseaUK
                [ 3 ] Institute of Medical ScienceUniversity of Tokyo TokyoJapan
                [ 4 ] Division of Biomedical Food ResearchNational Institute of Health Sciences TokyoJapan
                [ 5 ] Department of ZoologyUniversity of Oxford OxfordUK
                [ 6 ]Present address: The Biostatistics CenterKurume University 67 Asahi‐machi Fukuoka 830‐0011Japan
                [ 7 ]Present address: Public Health England, Microbiology Services Porton Down Salisbury Wiltshire SP4 0JGUK
                Author notes
                [*] [* ]For correspondence. E‐mail: s.k.sheppard@ 123456swansea.ac.uk ; Tel. 01792 +44 (0) 1792 606554; Fax +44 (0) 1792 513430.
                Article
                EMI13051
                10.1111/1462-2920.13051
                4862030
                26373338
                b5d90c8e-dc10-4f01-b836-dc087526e44d
                © 2015 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 07 March 2015
                : 07 September 2015
                : 08 September 2015
                Page count
                Pages: 11
                Funding
                Funded by: Medical Research Council
                Award ID: MR/L015080/1
                Funded by: Food Standards Agency
                Award ID: FS246004
                Funded by: Biotechnology and Biological Sciences Research Council
                Award ID: BB/I02464X/1
                Funded by: JSPS Research Fellowships
                Categories
                Research Articles
                Research Article
                Custom metadata
                2.0
                emi13051
                November 2015
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.1 mode:remove_FC converted:23.06.2016

                Microbiology & Virology
                Microbiology & Virology

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