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      Rapid Evolution of Virulence and Drug Resistance in the Emerging Zoonotic Pathogen Streptococcus suis

      research-article
      1 , * , 1 , 1 , 2 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 1 , 2 , 3 , 3 , 3 , 4 , 5 , 6 , 7 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 14 , 1 , 1 , 2 , 15 , 16 , 1
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          Abstract

          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, ∼40% of the ∼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 ∼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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          Most cited references89

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          Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial "pan-genome".

          The development of efficient and inexpensive genome sequencing methods has revolutionized the study of human bacterial pathogens and improved vaccine design. Unfortunately, the sequence of a single genome does not reflect how genetic variability drives pathogenesis within a bacterial species and also limits genome-wide screens for vaccine candidates or for antimicrobial targets. We have generated the genomic sequence of six strains representing the five major disease-causing serotypes of Streptococcus agalactiae, the main cause of neonatal infection in humans. Analysis of these genomes and those available in databases showed that the S. agalactiae species can be described by a pan-genome consisting of a core genome shared by all isolates, accounting for approximately 80% of any single genome, plus a dispensable genome consisting of partially shared and strain-specific genes. Mathematical extrapolation of the data suggests that the gene reservoir available for inclusion in the S. agalactiae pan-genome is vast and that unique genes will continue to be identified even after sequencing hundreds of genomes.
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            Improved tools for biological sequence comparison.

            We have developed three computer programs for comparisons of protein and DNA sequences. They can be used to search sequence data bases, evaluate similarity scores, and identify periodic structures based on local sequence similarity. The FASTA program is a more sensitive derivative of the FASTP program, which can be used to search protein or DNA sequence data bases and can compare a protein sequence to a DNA sequence data base by translating the DNA data base as it is searched. FASTA includes an additional step in the calculation of the initial pairwise similarity score that allows multiple regions of similarity to be joined to increase the score of related sequences. The RDF2 program can be used to evaluate the significance of similarity scores using a shuffling method that preserves local sequence composition. The LFASTA program can display all the regions of local similarity between two sequences with scores greater than a threshold, using the same scoring parameters and a similar alignment algorithm; these local similarities can be displayed as a "graphic matrix" plot or as individual alignments. In addition, these programs have been generalized to allow comparison of DNA or protein sequences based on a variety of alternative scoring matrices.
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              Rfam: an RNA family database.

              Rfam is a collection of multiple sequence alignments and covariance models representing non-coding RNA families. Rfam is available on the web in the UK at http://www.sanger.ac.uk/Software/Rfam/ and in the US at http://rfam.wustl.edu/. These websites allow the user to search a query sequence against a library of covariance models, and view multiple sequence alignments and family annotation. The database can also be downloaded in flatfile form and searched locally using the INFERNAL package (http://infernal.wustl.edu/). The first release of Rfam (1.0) contains 25 families, which annotate over 50 000 non-coding RNA genes in the taxonomic divisions of the EMBL nucleotide database.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2009
                15 July 2009
                : 4
                : 7
                : e6072
                Affiliations
                [1 ]The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom
                [2 ]Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam
                [3 ]Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam
                [4 ]Institute for Cell and Molecular Biosciences, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
                [5 ]The School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington Campus, Sutton Bonington, United Kingdom
                [6 ]Nuffield Department of Clinical Laboratory Sciences, Oxford University, John Radcliffe Hospital, Headington, United Kingdom
                [7 ]Department of Biological Sciences, University of Warwick, Coventry, United Kingdom
                [8 ]Centre for Preventative Medicine, Animal Health Trust, Newmarket, United Kingdom
                [9 ]Department of Biology, University of Copenhagen, Copenhagen, Denmark
                [10 ]Groupe de recherche sur les maladies infectieuses du porc (GREMIP), Université de Montréal, Montréal, Québec, Canada
                [11 ]Royal Veterinary College, Hatfield, United Kingdom
                [12 ]Animal Sciences Group (ASG), Wageningen UR, UR, Lelystad, The Netherlands
                [13 ]Department of Infectious Disease Epidemiology, Imperial College, London, United Kingdom
                [14 ]State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, China CDC, Beijing, China
                [15 ]Academic Medical Center-Center for Poverty-Related Communicable Diseases, University of Amsterdam, Amsterdam, The Netherlands
                [16 ]Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
                Columbia University, United States of America
                Author notes

                Conceived and designed the experiments: MTGH MK JAL PNW CGD AMW NC MG JDS HS BGS JX CY SDB BB CS DJM JP. Performed the experiments: MTGH HH MS THN IC AC IG KM MAQ CP ER SS TBC. Analyzed the data: MTGH HH MS NJC PI CS. Contributed reagents/materials/analysis tools: THN TBC NTHM TSD NTC JX CY. Wrote the paper: MTGH HH MS NJC JAL MG HS BGS SDB CS DJM JP.

                [¤a]

                Current address: School of Biological Sciences, University of Liverpool, Liverpool, United Kingdom

                [¤b]

                Current address: Veterinary Laboratories Agency, Weybridge, United Kingdom

                Article
                09-PONE-RA-09391
                10.1371/journal.pone.0006072
                2705793
                19603075
                5bd4d35e-d1e0-466f-8b2d-b8a25bdcbd15
                Holden et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 11 March 2009
                : 22 April 2009
                Page count
                Pages: 17
                Categories
                Research Article
                Microbiology/Medical Microbiology
                Microbiology/Microbial Evolution and Genomics
                Infectious Diseases/Antimicrobials and Drug Resistance

                Uncategorized
                Uncategorized

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