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      Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events.

      1 ,   2 , 3 , 3 , 3 , 4 , 5 , 6 , 3 , 7 , 8 , 9 , 3 , 3 , 3 , 3 , 10 , 11 , 3 , 3 , 12 , 13 , 14 , 15 , 16 , 3 , 17 , 18 , 13 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 30 , 31 , 32 , 33 , 26 , 32 , 32 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 39 , 42 , 26 , 43 , 44 , 45 , 45 , 46 , 11 , 47 , 48 , 49 , 49 , 49 , 49 , 26 , 8 , 3
      Nature genetics

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          Abstract

          The emergence of multidrug-resistant (MDR) typhoid is a major global health threat affecting many countries where the disease is endemic. Here whole-genome sequence analysis of 1,832 Salmonella enterica serovar Typhi (S. Typhi) identifies a single dominant MDR lineage, H58, that has emerged and spread throughout Asia and Africa over the last 30 years. Our analysis identifies numerous transmissions of H58, including multiple transfers from Asia to Africa and an ongoing, unrecognized MDR epidemic within Africa itself. Notably, our analysis indicates that H58 lineages are displacing antibiotic-sensitive isolates, transforming the global population structure of this pathogen. H58 isolates can harbor a complex MDR element residing either on transmissible IncHI1 plasmids or within multiple chromosomal integration sites. We also identify new mutations that define the H58 lineage. This phylogeographical analysis provides a framework to facilitate global management of MDR typhoid and is applicable to similar MDR lineages emerging in other bacterial species.

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          Most cited references46

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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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            Is Open Access

            genoPlotR: comparative gene and genome visualization in R

            Summary: The amount of gene and genome data obtained by next-generation sequencing technologies generates a need for comparative visualization tools. Complementing existing software for comparison and exploration of genomics data, genoPlotR automatically creates publication-grade linear maps of gene and genomes, in a highly automatic, flexible and reproducible way. Availability: genoPlotR is a platform-independent R package, available with full source code under a GPL2 license at R-Forge: http://genoplotr.r-forge.r-project.org/ Contact: lionel.guy@ebc.uu.se
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              Is Open Access

              Artemis and ACT: viewing, annotating and comparing sequences stored in a relational database

              Motivation: Artemis and Artemis Comparison Tool (ACT) have become mainstream tools for viewing and annotating sequence data, particularly for microbial genomes. Since its first release, Artemis has been continuously developed and supported with additional functionality for editing and analysing sequences based on feedback from an active user community of laboratory biologists and professional annotators. Nevertheless, its utility has been somewhat restricted by its limitation to reading and writing from flat files. Therefore, a new version of Artemis has been developed, which reads from and writes to a relational database schema, and allows users to annotate more complex, often large and fragmented, genome sequences. Results: Artemis and ACT have now been extended to read and write directly to the Generic Model Organism Database (GMOD, http://www.gmod.org) Chado relational database schema. In addition, a Gene Builder tool has been developed to provide structured forms and tables to edit coordinates of gene models and edit functional annotation, based on standard ontologies, controlled vocabularies and free text. Availability: Artemis and ACT are freely available (under a GPL licence) for download (for MacOSX, UNIX and Windows) at the Wellcome Trust Sanger Institute web sites: http://www.sanger.ac.uk/Software/Artemis/ http://www.sanger.ac.uk/Software/ACT/ Contact: artemis@sanger.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.
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                Author and article information

                Journal
                Nat. Genet.
                Nature genetics
                1546-1718
                1061-4036
                Jun 2015
                : 47
                : 6
                Affiliations
                [1 ] 1] Wellcome Trust Sanger Institute, Hinxton, UK. [2] Department of Microbiology, Addenbrooke's Hospital, Cambridge University Hospitals National Health Service (NHS) Foundation Trust, Cambridge, UK.
                [2 ] 1] Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. [2] Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK. [3] Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
                [3 ] Wellcome Trust Sanger Institute, Hinxton, UK.
                [4 ] Liverpool School of Tropical Medicine, Liverpool, UK.
                [5 ] 1] Wellcome Trust Sanger Institute, Hinxton, UK. [2] Institute of Food Research, Norwich Research Park, Norwich, UK.
                [6 ] 1] Wellcome Trust Sanger Institute, Hinxton, UK. [2] Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
                [7 ] Institut Pasteur, Unité des Bactéries Pathogènes Entériques, Paris, France.
                [8 ] Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Victoria, Australia.
                [9 ] 1] Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Victoria, Australia. [2] Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Melbourne, Victoria, Australia.
                [10 ] Institute of Biomedical Research, School of Immunity and Infection, College of Medicine and Dental Sciences, University of Birmingham, Birmingham, UK.
                [11 ] Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
                [12 ] 1] Kenya Medical Research Institute (KEMRI), Nairobi, Kenya. [2] Centers for Disease Control and Prevention, Atlanta, Georgia, USA. [3] Emory Global Health Institute, Atlanta, Georgia, USA.
                [13 ] Centre for the Mathematical Modelling of Infectious Diseases, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
                [14 ] 1] Wellcome Trust Sanger Institute, Hinxton, UK. [2] Kenya Medical Research Institute (KEMRI), Nairobi, Kenya.
                [15 ] Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
                [16 ] Malawi-Liverpool Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi.
                [17 ] 1] Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. [2] Department of Microbiology and Immunology, Katholieke Universiteit (KU) Leuven, University of Leuven, Leuven, Belgium.
                [18 ] 1] National Institute for Biomedical Research, Kinshasa, Democratic Republic of the Congo. [2] University Hospital of Kinshasa, Kinshasa, Democratic Republic of the Congo.
                [19 ] 1] Malawi-Liverpool Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi. [2] Microbiology Department, College of Medicine, University of Malawi, Blantyre, Malawi.
                [20 ] Departamento de Desarrollo Biotecnológico, Instituto de Higiene, Facultad de Medicina, Montevideo, Uruguay.
                [21 ] Ministry of Health, Suva, Fiji.
                [22 ] Fiji Health Sector Support Program, Suva, Fiji.
                [23 ] National Institute of Cholera and Enteric Diseases, Kolkata, India.
                [24 ] International Vaccine Institute, Department of Epidemiology, Seoul, Republic of Korea.
                [25 ] Enteropathogen Division, Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) Carlos G. Malbran Institute, Buenos Aires, Argentina.
                [26 ] 1] Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. [2] Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK.
                [27 ] 1] Division of Pediatric Infectious Diseases, University of Nebraska Medical Center, Omaha, Nebraska, USA. [2] University of Abuja Teaching Hospital, Abuja, Nigeria. [3] Bingham University, Karu, Nigeria.
                [28 ] 1] Wellcome Trust Sanger Institute, Hinxton, UK. [2] Institute of Biomedical Research, School of Immunity and Infection, College of Medicine and Dental Sciences, University of Birmingham, Birmingham, UK. [3] Novartis Vaccines Institute for Global Health, Siena, Italy.
                [29 ] Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK.
                [30 ] Centre for Enteric Diseases, National Institute for Communicable Diseases, Division in the National Health Laboratory Service, University of the Witwatersrand, Johannesburg, South Africa.
                [31 ] 1] Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, UK. [2] Graduate School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan.
                [32 ] Patan Academy of Health Sciences, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Kathmandu, Nepal.
                [33 ] 1] Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. [2] Murdoch Childrens Research Institute, Melbourne, Victoria, Australia.
                [34 ] Enteric and Leptospira Reference Laboratory, Institute of Environmental Science and Research, Ltd. (ESR), Porirua, New Zealand.
                [35 ] National Centre for Biosecurity and Infectious Disease, Institute of Environmental Science and Research, Porirua, New Zealand.
                [36 ] Samoa Ministry of Health, Apia, Samoa.
                [37 ] National Influenza Center, World Health Organization, Center for Communicable Disease Control, Suva, Fiji.
                [38 ] Department of Microbiology, Hasanuddin University, Makassar, Indonesia.
                [39 ] 1] Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK. [2] Lao Oxford Mahosot Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos.
                [40 ] Kenya Medical Research Institute (KEMRI), Nairobi, Kenya.
                [41 ] National Health Services, Tupua Tamasese Meaole Hospital, Apia, Samoa.
                [42 ] Lao Oxford Mahosot Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Laos.
                [43 ] 1] Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. [2] Paediatric Emergency Medicine, Chelsea and Westminster Hospital, London, UK.
                [44 ] Centre for International Health and Otago International Health Research Network, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
                [45 ] Salmonella Reference Service, Public Health England, Colindale, London, UK.
                [46 ] Emerging Disease Surveillance and Response, Division of Pacific Technical Support, World Health Organization, Suva, Fiji.
                [47 ] 1] Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK. [2] Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. [3] Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia.
                [48 ] Cambodia-Oxford Medical Research Unit, Angkor Hospital for Children, Siem Reap, Cambodia.
                [49 ] Microbiological Diagnostic Unit-Public Health Laboratory, Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
                Article
                ng.3281 NIHMS793848
                10.1038/ng.3281
                25961941
                bd9800e4-f6b1-42e0-b417-60ef1401bc14
                History

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