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      Population genomics of hypervirulent Klebsiella pneumoniae clonal-group 23 reveals early emergence and rapid global dissemination

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          Abstract

          Severe liver abscess infections caused by hypervirulent clonal-group CG23 Klebsiella pneumoniae have been increasingly reported since the mid-1980s. Strains typically possess several virulence factors including an integrative, conjugative element ICE Kp encoding the siderophore yersiniabactin and genotoxin colibactin. Here we investigate CG23’s evolutionary history, showing several deep-branching sublineages associated with distinct ICE Kp acquisitions. Over 80% of liver abscess isolates belong to sublineage CG23-I, which emerged in ~1928 following acquisition of ICE Kp10 (encoding yersiniabactin and colibactin), and then disseminated globally within the human population. CG23-I’s distinguishing feature is the colibactin synthesis locus, which reportedly promotes gut colonisation and metastatic infection in murine models. These data show circulation of CG23 K. pneumoniae decades before the liver abscess epidemic was first recognised, and provide a framework for future epidemiological and experimental studies of hypervirulent K. pneumoniae. To support such studies we present an open access, completely sequenced CG23-I human liver abscess isolate, SGH10.

          Abstract

          Since the 1980s, hypervirulent clonal-group CG23 serotype K1 Klebsiella pneumoniae has been recognised as a prominent cause of community-acquired liver abscess and other severe infections. Here, the authors investigate the genomic evolutionary history of CG23 and suggest a new reference strain for CG23.

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          Most cited references53

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          Hypervirulent (hypermucoviscous) Klebsiella pneumoniae

          A new hypervirulent (hypermucoviscous) variant of Klebsiella pneumoniae has emerged. First described in the Asian Pacific Rim, it now increasingly recognized in Western countries. Defining clinical features are the ability to cause serious, life-threatening community-acquired infection in younger healthy hosts, including liver abscess, pneumonia, meningitis and endophthalmitis and the ability to metastatically spread, an unusual feature for enteric Gram-negative bacilli in the non-immunocompromised. Despite infecting a healthier population, significant morbidity and mortality occurs. Although epidemiologic features are still being defined, colonization, particularly intestinal colonization, appears to be a critical step leading to infection. However the route of entry remains unclear. The majority of cases described to date are in Asians, raising the issue of a genetic predisposition vs. geospecific strain acquisition. The traits that enhance its virulence when compared with “classical” K. pneumoniae are the ability to more efficiently acquire iron and perhaps an increase in capsule production, which confers the hypermucoviscous phenotype. An objective diagnostic test suitable for routine use in the clinical microbiology laboratory is needed. If/when these strains become increasingly resistant to antimicrobials, we will be faced with a frightening clinical scenario.
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            Artemis: sequence visualization and annotation

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              Klebsiella pneumoniae liver abscess: a new invasive syndrome.

              Klebsiella pneumoniae is a well known human nosocomial pathogen. Most community-acquired K pneumoniae infections cause pneumonia or urinary tract infections. During the past two decades, however, a distinct invasive syndrome that causes liver abscesses has been increasingly reported in Asia, and this syndrome is emerging as a global disease. In this Review, we summarise the clinical presentation and management as well the microbiological aspects of this invasive disease. Diabetes mellitus and two specific capsular types in the bacterium predispose a patient to the development of liver abscesses and the following metastatic complications: bacteraemia, meningitis, endophthalmitis, and necrotising fasciitis. For patients with this invasive syndrome, appropriate antimicrobial treatment combined with percutaneous drainage of liver abscesses increases their chances of survival. Rapid detection of the hypervirulent strain that causes this syndrome allows earlier diagnosis and treatment, thus minimising the occurrence of sequelae and improving clinical outcomes. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                kholt@unimelb.edu.au
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                13 July 2018
                13 July 2018
                2018
                : 9
                : 2703
                Affiliations
                [1 ]ISNI 0000 0001 2179 088X, GRID grid.1008.9, Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, , University of Melbourne, ; Parkville, Victoria 3010 Australia
                [2 ]ISNI 0000 0001 2180 6431, GRID grid.4280.e, Department of Biochemistry, Yong Loo Lin School of Medicine, , National University of Singapore, ; Singapore, 119228 Singapore
                [3 ]ISNI 0000 0001 2180 6431, GRID grid.4280.e, Department of Medicine, Yong Loo Lin School of Medicine, , National University of Singapore, ; Singapore, 119228 Singapore
                [4 ]ISNI 0000 0000 9486 5048, GRID grid.163555.1, Department of Infectious Diseases, , Singapore General Hospital, ; Singapore, 169608 Singapore
                [5 ]ISNI 0000 0000 9486 5048, GRID grid.163555.1, Department of Microbiology, , Singapore General Hospital, ; Singapore, 169608 Singapore
                [6 ]Institut Pasteur, Biodiversity and Epidemiology of Bacterial Pathogens, 75015 Paris, France
                [7 ]ISNI 0000 0004 0425 469X, GRID grid.8991.9, The London School of Hygiene and Tropical Medicine, ; London, WC1E 7HT United Kingdom
                Author information
                http://orcid.org/0000-0002-2916-2818
                http://orcid.org/0000-0003-3949-2471
                Article
                5114
                10.1038/s41467-018-05114-7
                6045662
                30006589
                43432d51-5b8e-4560-ab98-2baf492a9e4b
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 25 January 2018
                : 31 May 2018
                Funding
                Funded by: FundRef https://doi.org/10.13039/100000865, Bill and Melinda Gates Foundation;
                Award ID: OPP1175797
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100000925, Department of Health | National Health and Medical Research Council (NHMRC);
                Award ID: 1061409
                Award Recipient :
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