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    Genomic evidence for the evolution of Streptococcus equi: host restriction, increased virulence, and genetic exchange with human pathogens.
    Holden, MTG ; Heather, Z ; Paillot, R ; Steward, KF ; Webb, K ; Ainslie, F ; Jourdan, T ; Bason, NC ; Holroyd, NE ; Mungall, K ; Quail, MA ; Sanders, M ; Simmonds, M ; Willey, D ; Brooks, K ; Aanensen, DM ; Spratt, BG ; Jolley, KA ; Maiden, MCJ ; Kehoe, M ; Chanter, N ; Bentley, SD ; Robinson, C ; Maskell, DJ ; Parkhill, J ; Waller, AS ; Wessels, MR (Public Library of Science (PLoS), 2009-03)
    The continued evolution of bacterial pathogens has major implications for both human and animal disease, but the exchange of genetic material between host-restricted pathogens is rarely considered. Streptococcus equi subspecies equi (S. equi) is a host-restricted pathogen of horses that has evolved from the zoonotic pathogen Streptococcus equi subspecies zooepidemicus (S. zooepidemicus). These pathogens share approximately 80% genome sequence identity with the important human pathogen Streptococcus pyogenes. We sequenced and compared the genomes of S. equi 4047 and S. zooepidemicus H70 and screened S. equi and S. zooepidemicus strains from around the world to uncover evidence of the genetic events that have shaped the evolution of the S. equi genome and led to its emergence as a host-restricted pathogen. Our analysis provides evidence of functional loss due to mutation and deletion, coupled with pathogenic specialization through the acquisition of bacteriophage encoding a phospholipase A(2) toxin, and four superantigens, and an integrative conjugative element carrying a novel iron acquisition system with similarity to the high pathogenicity island of Yersinia pestis. We also highlight that S. equi, S. zooepidemicus, and S. pyogenes share a common phage pool that enhances cross-species pathogen evolution. We conclude that the complex interplay of functional loss, pathogenic specialization, and genetic exchange between S. equi, S. zooepidemicus, and S. pyogenes continues to influence the evolution of these important streptococci.
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    Post-assembly modification of Bordetella bronchiseptica O polysaccharide by a novel periplasmic enzyme encoded by wbmE.
    King, JD ; Vinogradov, E ; Preston, A ; Li, J ; Maskell, DJ (Elsevier BV, 2009-01-16)
    Bordetella bronchiseptica is a pathogen of humans and animals that colonizes the respiratory tract. It produces a lipopolysaccharide O antigen that contains a homopolymer of 2,3-dideoxy-2,3-diacetamido-L-galacturonic acid (L-GalNAc3NAcA). Some of these sugars are found in the uronamide form (L-GalNAc3NAcAN), and there is no discernible pattern in the distribution of amides along the chain. A B. bronchiseptica wbmE mutant expresses an O polysaccharide unusually rich in uronamides. The WbmE protein localizes to the periplasm and catalyzes the deamidation of uronamide-rich O chains in lipopolysaccharide purified from the mutant, to attain a wild-type uronamide/uronic acid ratio. WbmE is a member of the papain-like transglutaminase superfamily, and this categorization is consistent with a deamidase role. The periplasmic location of WbmE and its acceptance of complete lipopolysaccharide as substrate indicate that it operates at a late stage in lipopolysaccharide biosynthesis, after polymerization and export of the O chain from the cytoplasm. This is the first report of such a modification of O antigen after assembly. The expression of wbmE is controlled by the Bordetella virulence gene two-component regulatory system, BvgAS, suggesting that this deamidation is a novel mechanism by which these bacteria modify their cell surface charge in response to environmental stimuli.
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    Evidence for niche adaptation in the genome of the bovine pathogen Streptococcus uberis.
    Ward, PN ; Holden, MTG ; Leigh, JA ; Lennard, N ; Bignell, A ; Barron, A ; Clark, L ; Quail, MA ; Woodward, J ; Barrell, BG ; Egan, SA ; Field, TR ; Maskell, D ; Kehoe, M ; Dowson, CG ; Chanter, N ; Whatmore, AM ; Bentley, SD ; Parkhill, J (Springer Science and Business Media LLC, 2009-01-28)
    BACKGROUND: Streptococcus uberis, a Gram positive bacterial pathogen responsible for a significant proportion of bovine mastitis in commercial dairy herds, colonises multiple body sites of the cow including the gut, genital tract and mammary gland. Comparative analysis of the complete genome sequence of S. uberis strain 0140J was undertaken to help elucidate the biology of this effective bovine pathogen. RESULTS: The genome revealed 1,825 predicted coding sequences (CDSs) of which 62 were identified as pseudogenes or gene fragments. Comparisons with related pyogenic streptococci identified a conserved core (40%) of orthologous CDSs. Intriguingly, S. uberis 0140J displayed a lower number of mobile genetic elements when compared with other pyogenic streptococci, however bacteriophage-derived islands and a putative genomic island were identified. Comparative genomics analysis revealed most similarity to the genomes of Streptococcus agalactiae and Streptococcus equi subsp. zooepidemicus. In contrast, streptococcal orthologs were not identified for 11% of the CDSs, indicating either unique retention of ancestral sequence, or acquisition of sequence from alternative sources. Functions including transport, catabolism, regulation and CDSs encoding cell envelope proteins were over-represented in this unique gene set; a limited array of putative virulence CDSs were identified. CONCLUSION: S. uberis utilises nutritional flexibility derived from a diversity of metabolic options to successfully occupy a discrete ecological niche. The features observed in S. uberis are strongly suggestive of an opportunistic pathogen adapted to challenging and changing environmental parameters.
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    Rapid evolution of virulence and drug resistance in the emerging zoonotic pathogen Streptococcus suis.
    Holden, MTG ; Hauser, H ; Sanders, M ; Ngo, TH ; Cherevach, I ; Cronin, A ; Goodhead, I ; Mungall, K ; Quail, MA ; Price, C ; Rabbinowitsch, E ; Sharp, S ; Croucher, NJ ; Chieu, TB ; Mai, NTH ; Diep, TS ; Chinh, NT ; Kehoe, M ; Leigh, JA ; Ward, PN ; Dowson, CG ; Whatmore, AM ; Chanter, N ; Iversen, P ; Gottschalk, M ; Slater, JD ; Smith, HE ; Spratt, BG ; Xu, J ; Ye, C ; Bentley, S ; Barrell, BG ; Schultsz, C ; Maskell, DJ ; Parkhill, J ; Ratner, AJ (Public Library of Science (PLoS), 2009-07-15)
    BACKGROUND: Streptococcus suis is a zoonotic pathogen that infects pigs and can occasionally cause serious infections in humans. S. suis infections occur sporadically in human Europe and North America, but a recent major outbreak has been described in China with high levels of mortality. The mechanisms of S. suis pathogenesis in humans and pigs are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: The sequencing of whole genomes of S. suis isolates provides opportunities to investigate the genetic basis of infection. Here we describe whole genome sequences of three S. suis strains from the same lineage: one from European pigs, and two from human cases from China and Vietnam. Comparative genomic analysis was used to investigate the variability of these strains. S. suis is phylogenetically distinct from other Streptococcus species for which genome sequences are currently available. Accordingly, approximately 40% of the approximately 2 Mb genome is unique in comparison to other Streptococcus species. Finer genomic comparisons within the species showed a high level of sequence conservation; virtually all of the genome is common to the S. suis strains. The only exceptions are three approximately 90 kb regions, present in the two isolates from humans, composed of integrative conjugative elements and transposons. Carried in these regions are coding sequences associated with drug resistance. In addition, small-scale sequence variation has generated pseudogenes in putative virulence and colonization factors. CONCLUSIONS/SIGNIFICANCE: The genomic inventories of genetically related S. suis strains, isolated from distinct hosts and diseases, exhibit high levels of conservation. However, the genomes provide evidence that horizontal gene transfer has contributed to the evolution of drug resistance.
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    Fall of the Berlin Wall: A Victory for Europe
    SUDER, G (Bloomberg, 2009-11-05)
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    International Business
    Suder, GS (Sage Publications, 2009)
    The Sage Course Companion in International Business is an easy-to-navigate support guide to the International Business curriculum. It allows readers to extend their understanding of key concepts and enhance their thinking skills in line with course requirements. This book also provides guidance on essential study skills and advice on developing critical thinking about international business.
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    Complexity, Error and Failure: Reconceptualising the Epistemological Foundations of Contemporary Liberal Democratic Politics
    LITTLE, A (Macquarie University Faculty of Arts Politics and International Relations, 2009)