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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in <italic>Klebsiella pneumoniae</italic>
, an urgent threat to public health</title>
<author><name sortKey="Holt, Kathryn E" sort="Holt, Kathryn E" uniqKey="Holt K" first="Kathryn E." last="Holt">Kathryn E. Holt</name>
<affiliation><nlm:aff id="aff1">Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute,<institution>The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wertheim, Heiman" sort="Wertheim, Heiman" uniqKey="Wertheim H" first="Heiman" last="Wertheim">Heiman Wertheim</name>
<affiliation><nlm:aff id="aff3">Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme,<institution>National Hospital for Tropical Diseases</institution>
, Hanoi,<institution>Vietnam</institution>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff4">Nuffield Department of Clinical Medicine, Centre for Tropical Medicine,<institution>University of Oxford</institution>
, OX3 7BN Oxford,<country>United Kingdom</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zadoks, Ruth N" sort="Zadoks, Ruth N" uniqKey="Zadoks R" first="Ruth N." last="Zadoks">Ruth N. Zadoks</name>
<affiliation><nlm:aff id="aff5">Quality Milk Production Services,<institution>Cornell University</institution>
, Ithaca,<addr-line>NY</addr-line>
14853;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff6">Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences,<institution>University of Glasgow</institution>
, G12 8QQ Glasgow,<country>United Kingdom</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Baker, Stephen" sort="Baker, Stephen" uniqKey="Baker S" first="Stephen" last="Baker">Stephen Baker</name>
<affiliation><nlm:aff id="aff7">The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme,<institution>Oxford University Clinical Research Unit</institution>
, Ho Chi Minh City,<country>Vietnam</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Whitehouse, Chris A" sort="Whitehouse, Chris A" uniqKey="Whitehouse C" first="Chris A." last="Whitehouse">Chris A. Whitehouse</name>
<affiliation><nlm:aff id="aff8"><institution>United States Army Medical Research Institute of Infectious Diseases</institution>
, Fort Detrick,<addr-line>MD</addr-line>
21702;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Dance, David" sort="Dance, David" uniqKey="Dance D" first="David" last="Dance">David Dance</name>
<affiliation><nlm:aff id="aff4">Nuffield Department of Clinical Medicine, Centre for Tropical Medicine,<institution>University of Oxford</institution>
, OX3 7BN Oxford,<country>United Kingdom</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff9">Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit, Microbiology Laboratory,<institution>Mahosot Hospital</institution>
, Vientiane,<country>Lao People’s Democratic Republic</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jenney, Adam" sort="Jenney, Adam" uniqKey="Jenney A" first="Adam" last="Jenney">Adam Jenney</name>
<affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff10">Departmemt Infectious Diseases and Microbiology Unit,<institution>The Alfred Hospital</institution>
, Melbourne, VIC 3004, Australia;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Connor, Thomas R" sort="Connor, Thomas R" uniqKey="Connor T" first="Thomas R." last="Connor">Thomas R. Connor</name>
<affiliation><nlm:aff id="aff11">Pathogen Genomics,<institution>Wellcome Trust Sanger Centre</institution>
, CB10 1SA Cambridge,<country>United Kingdom</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff12">Cardiff University School of Biosciences,<institution>Cardiff University</institution>
, Cardiff, Wales, CF10 3AX,<country>United Kingdom</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hsu, Li Yang" sort="Hsu, Li Yang" uniqKey="Hsu L" first="Li Yang" last="Hsu">Li Yang Hsu</name>
<affiliation><nlm:aff id="aff13">Department of Medicine,<institution>National University Health System</institution>
,<country>Singapore</country>
119228;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Severin, Juliette" sort="Severin, Juliette" uniqKey="Severin J" first="Juliëtte" last="Severin">Juliëtte Severin</name>
<affiliation><nlm:aff id="aff14">Department of Medical Microbiology and Infectious Diseases,<institution>Erasmus University Medical Center</institution>
, 3015 CE Rotterdam,<country>The Netherlands</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Brisse, Sylvain" sort="Brisse, Sylvain" uniqKey="Brisse S" first="Sylvain" last="Brisse">Sylvain Brisse</name>
<affiliation><nlm:aff id="aff15">Microbial Evolutionary Genomics,<institution>Institut Pasteur</institution>
, CNRS, UMR3525, Paris,<country>France</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cao, Hanwei" sort="Cao, Hanwei" uniqKey="Cao H" first="Hanwei" last="Cao">Hanwei Cao</name>
<affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff16"><institution>Peter Doherty Institute, The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wilksch, Jonathan" sort="Wilksch, Jonathan" uniqKey="Wilksch J" first="Jonathan" last="Wilksch">Jonathan Wilksch</name>
<affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff16"><institution>Peter Doherty Institute, The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gorrie, Claire" sort="Gorrie, Claire" uniqKey="Gorrie C" first="Claire" last="Gorrie">Claire Gorrie</name>
<affiliation><nlm:aff id="aff1">Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute,<institution>The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff16"><institution>Peter Doherty Institute, The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Schultz, Mark B" sort="Schultz, Mark B" uniqKey="Schultz M" first="Mark B." last="Schultz">Mark B. Schultz</name>
<affiliation><nlm:aff id="aff1">Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute,<institution>The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Edwards, David J" sort="Edwards, David J" uniqKey="Edwards D" first="David J." last="Edwards">David J. Edwards</name>
<affiliation><nlm:aff id="aff1">Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute,<institution>The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nguyen, Kinh Van" sort="Nguyen, Kinh Van" uniqKey="Nguyen K" first="Kinh Van" last="Nguyen">Kinh Van Nguyen</name>
<affiliation><nlm:aff id="aff17"><institution>National Hospital for Tropical Diseases</institution>
, Hanoi,<country>Vietnam</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nguyen, Trung Vu" sort="Nguyen, Trung Vu" uniqKey="Nguyen T" first="Trung Vu" last="Nguyen">Trung Vu Nguyen</name>
<affiliation><nlm:aff id="aff17"><institution>National Hospital for Tropical Diseases</institution>
, Hanoi,<country>Vietnam</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Dao, Trinh Tuyet" sort="Dao, Trinh Tuyet" uniqKey="Dao T" first="Trinh Tuyet" last="Dao">Trinh Tuyet Dao</name>
<affiliation><nlm:aff id="aff17"><institution>National Hospital for Tropical Diseases</institution>
, Hanoi,<country>Vietnam</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mensink, Martijn" sort="Mensink, Martijn" uniqKey="Mensink M" first="Martijn" last="Mensink">Martijn Mensink</name>
<affiliation><nlm:aff id="aff5">Quality Milk Production Services,<institution>Cornell University</institution>
, Ithaca,<addr-line>NY</addr-line>
14853;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Minh, Vien Le" sort="Minh, Vien Le" uniqKey="Minh V" first="Vien Le" last="Minh">Vien Le Minh</name>
<affiliation><nlm:aff id="aff7">The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme,<institution>Oxford University Clinical Research Unit</institution>
, Ho Chi Minh City,<country>Vietnam</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff18">Division of Infectious Diseases, Department of Medicine,<institution>University of California, San Francisco</institution>
,<addr-line>CA 94118-6215</addr-line>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nhu, Nguyen Thi Khanh" sort="Nhu, Nguyen Thi Khanh" uniqKey="Nhu N" first="Nguyen Thi Khanh" last="Nhu">Nguyen Thi Khanh Nhu</name>
<affiliation><nlm:aff id="aff7">The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme,<institution>Oxford University Clinical Research Unit</institution>
, Ho Chi Minh City,<country>Vietnam</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff19">School of Chemistry and Molecular Biosciences,<institution>The University of Queensland</institution>
, Brisbane, QLD 4072,<country>Australia</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Schultsz, Constance" sort="Schultsz, Constance" uniqKey="Schultsz C" first="Constance" last="Schultsz">Constance Schultsz</name>
<affiliation><nlm:aff id="aff7">The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme,<institution>Oxford University Clinical Research Unit</institution>
, Ho Chi Minh City,<country>Vietnam</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff24">Academic Medical Center,<institution>University of Amsterdam</institution>
, 1012 WX Amsterdam,<country>The Netherlands</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kuntaman, Kuntaman" sort="Kuntaman, Kuntaman" uniqKey="Kuntaman K" first="Kuntaman" last="Kuntaman">Kuntaman Kuntaman</name>
<affiliation><nlm:aff id="aff21">Department of Clinical Microbiology, Dr. Soetomo Academic Hospital – School of Medicine,<institution>Airlangga University</institution>
, Surabaya, Jawa Timur,<country>Indonesia</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Newton, Paul N" sort="Newton, Paul N" uniqKey="Newton P" first="Paul N." last="Newton">Paul N. Newton</name>
<affiliation><nlm:aff id="aff4">Nuffield Department of Clinical Medicine, Centre for Tropical Medicine,<institution>University of Oxford</institution>
, OX3 7BN Oxford,<country>United Kingdom</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff9">Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit, Microbiology Laboratory,<institution>Mahosot Hospital</institution>
, Vientiane,<country>Lao People’s Democratic Republic</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Moore, Catrin E" sort="Moore, Catrin E" uniqKey="Moore C" first="Catrin E." last="Moore">Catrin E. Moore</name>
<affiliation><nlm:aff id="aff4">Nuffield Department of Clinical Medicine, Centre for Tropical Medicine,<institution>University of Oxford</institution>
, OX3 7BN Oxford,<country>United Kingdom</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff9">Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit, Microbiology Laboratory,<institution>Mahosot Hospital</institution>
, Vientiane,<country>Lao People’s Democratic Republic</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Strugnell, Richard A" sort="Strugnell, Richard A" uniqKey="Strugnell R" first="Richard A." last="Strugnell">Richard A. Strugnell</name>
<affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff16"><institution>Peter Doherty Institute, The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Thomson, Nicholas R" sort="Thomson, Nicholas R" uniqKey="Thomson N" first="Nicholas R." last="Thomson">Nicholas R. Thomson</name>
<affiliation><nlm:aff id="aff11">Pathogen Genomics,<institution>Wellcome Trust Sanger Centre</institution>
, CB10 1SA Cambridge,<country>United Kingdom</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff25">Department of Pathogen Molecular Biology,<institution>The London School of Hygiene and Tropical Medicine</institution>
, WC1E 7HT London,<country>United Kingdom</country>
</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">26100894</idno>
<idno type="pmc">4500264</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500264</idno>
<idno type="RBID">PMC:4500264</idno>
<idno type="doi">10.1073/pnas.1501049112</idno>
<date when="2015">2015</date>
<idno type="wicri:Area/Pmc/Corpus">000227</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000227</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in <italic>Klebsiella pneumoniae</italic>
, an urgent threat to public health</title>
<author><name sortKey="Holt, Kathryn E" sort="Holt, Kathryn E" uniqKey="Holt K" first="Kathryn E." last="Holt">Kathryn E. Holt</name>
<affiliation><nlm:aff id="aff1">Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute,<institution>The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wertheim, Heiman" sort="Wertheim, Heiman" uniqKey="Wertheim H" first="Heiman" last="Wertheim">Heiman Wertheim</name>
<affiliation><nlm:aff id="aff3">Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme,<institution>National Hospital for Tropical Diseases</institution>
, Hanoi,<institution>Vietnam</institution>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff4">Nuffield Department of Clinical Medicine, Centre for Tropical Medicine,<institution>University of Oxford</institution>
, OX3 7BN Oxford,<country>United Kingdom</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zadoks, Ruth N" sort="Zadoks, Ruth N" uniqKey="Zadoks R" first="Ruth N." last="Zadoks">Ruth N. Zadoks</name>
<affiliation><nlm:aff id="aff5">Quality Milk Production Services,<institution>Cornell University</institution>
, Ithaca,<addr-line>NY</addr-line>
14853;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff6">Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences,<institution>University of Glasgow</institution>
, G12 8QQ Glasgow,<country>United Kingdom</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Baker, Stephen" sort="Baker, Stephen" uniqKey="Baker S" first="Stephen" last="Baker">Stephen Baker</name>
<affiliation><nlm:aff id="aff7">The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme,<institution>Oxford University Clinical Research Unit</institution>
, Ho Chi Minh City,<country>Vietnam</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Whitehouse, Chris A" sort="Whitehouse, Chris A" uniqKey="Whitehouse C" first="Chris A." last="Whitehouse">Chris A. Whitehouse</name>
<affiliation><nlm:aff id="aff8"><institution>United States Army Medical Research Institute of Infectious Diseases</institution>
, Fort Detrick,<addr-line>MD</addr-line>
21702;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Dance, David" sort="Dance, David" uniqKey="Dance D" first="David" last="Dance">David Dance</name>
<affiliation><nlm:aff id="aff4">Nuffield Department of Clinical Medicine, Centre for Tropical Medicine,<institution>University of Oxford</institution>
, OX3 7BN Oxford,<country>United Kingdom</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff9">Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit, Microbiology Laboratory,<institution>Mahosot Hospital</institution>
, Vientiane,<country>Lao People’s Democratic Republic</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Jenney, Adam" sort="Jenney, Adam" uniqKey="Jenney A" first="Adam" last="Jenney">Adam Jenney</name>
<affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff10">Departmemt Infectious Diseases and Microbiology Unit,<institution>The Alfred Hospital</institution>
, Melbourne, VIC 3004, Australia;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Connor, Thomas R" sort="Connor, Thomas R" uniqKey="Connor T" first="Thomas R." last="Connor">Thomas R. Connor</name>
<affiliation><nlm:aff id="aff11">Pathogen Genomics,<institution>Wellcome Trust Sanger Centre</institution>
, CB10 1SA Cambridge,<country>United Kingdom</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff12">Cardiff University School of Biosciences,<institution>Cardiff University</institution>
, Cardiff, Wales, CF10 3AX,<country>United Kingdom</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hsu, Li Yang" sort="Hsu, Li Yang" uniqKey="Hsu L" first="Li Yang" last="Hsu">Li Yang Hsu</name>
<affiliation><nlm:aff id="aff13">Department of Medicine,<institution>National University Health System</institution>
,<country>Singapore</country>
119228;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Severin, Juliette" sort="Severin, Juliette" uniqKey="Severin J" first="Juliëtte" last="Severin">Juliëtte Severin</name>
<affiliation><nlm:aff id="aff14">Department of Medical Microbiology and Infectious Diseases,<institution>Erasmus University Medical Center</institution>
, 3015 CE Rotterdam,<country>The Netherlands</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Brisse, Sylvain" sort="Brisse, Sylvain" uniqKey="Brisse S" first="Sylvain" last="Brisse">Sylvain Brisse</name>
<affiliation><nlm:aff id="aff15">Microbial Evolutionary Genomics,<institution>Institut Pasteur</institution>
, CNRS, UMR3525, Paris,<country>France</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Cao, Hanwei" sort="Cao, Hanwei" uniqKey="Cao H" first="Hanwei" last="Cao">Hanwei Cao</name>
<affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff16"><institution>Peter Doherty Institute, The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wilksch, Jonathan" sort="Wilksch, Jonathan" uniqKey="Wilksch J" first="Jonathan" last="Wilksch">Jonathan Wilksch</name>
<affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff16"><institution>Peter Doherty Institute, The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Gorrie, Claire" sort="Gorrie, Claire" uniqKey="Gorrie C" first="Claire" last="Gorrie">Claire Gorrie</name>
<affiliation><nlm:aff id="aff1">Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute,<institution>The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff16"><institution>Peter Doherty Institute, The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Schultz, Mark B" sort="Schultz, Mark B" uniqKey="Schultz M" first="Mark B." last="Schultz">Mark B. Schultz</name>
<affiliation><nlm:aff id="aff1">Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute,<institution>The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Edwards, David J" sort="Edwards, David J" uniqKey="Edwards D" first="David J." last="Edwards">David J. Edwards</name>
<affiliation><nlm:aff id="aff1">Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute,<institution>The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nguyen, Kinh Van" sort="Nguyen, Kinh Van" uniqKey="Nguyen K" first="Kinh Van" last="Nguyen">Kinh Van Nguyen</name>
<affiliation><nlm:aff id="aff17"><institution>National Hospital for Tropical Diseases</institution>
, Hanoi,<country>Vietnam</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nguyen, Trung Vu" sort="Nguyen, Trung Vu" uniqKey="Nguyen T" first="Trung Vu" last="Nguyen">Trung Vu Nguyen</name>
<affiliation><nlm:aff id="aff17"><institution>National Hospital for Tropical Diseases</institution>
, Hanoi,<country>Vietnam</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Dao, Trinh Tuyet" sort="Dao, Trinh Tuyet" uniqKey="Dao T" first="Trinh Tuyet" last="Dao">Trinh Tuyet Dao</name>
<affiliation><nlm:aff id="aff17"><institution>National Hospital for Tropical Diseases</institution>
, Hanoi,<country>Vietnam</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mensink, Martijn" sort="Mensink, Martijn" uniqKey="Mensink M" first="Martijn" last="Mensink">Martijn Mensink</name>
<affiliation><nlm:aff id="aff5">Quality Milk Production Services,<institution>Cornell University</institution>
, Ithaca,<addr-line>NY</addr-line>
14853;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Minh, Vien Le" sort="Minh, Vien Le" uniqKey="Minh V" first="Vien Le" last="Minh">Vien Le Minh</name>
<affiliation><nlm:aff id="aff7">The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme,<institution>Oxford University Clinical Research Unit</institution>
, Ho Chi Minh City,<country>Vietnam</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff18">Division of Infectious Diseases, Department of Medicine,<institution>University of California, San Francisco</institution>
,<addr-line>CA 94118-6215</addr-line>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Nhu, Nguyen Thi Khanh" sort="Nhu, Nguyen Thi Khanh" uniqKey="Nhu N" first="Nguyen Thi Khanh" last="Nhu">Nguyen Thi Khanh Nhu</name>
<affiliation><nlm:aff id="aff7">The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme,<institution>Oxford University Clinical Research Unit</institution>
, Ho Chi Minh City,<country>Vietnam</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff19">School of Chemistry and Molecular Biosciences,<institution>The University of Queensland</institution>
, Brisbane, QLD 4072,<country>Australia</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Schultsz, Constance" sort="Schultsz, Constance" uniqKey="Schultsz C" first="Constance" last="Schultsz">Constance Schultsz</name>
<affiliation><nlm:aff id="aff7">The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme,<institution>Oxford University Clinical Research Unit</institution>
, Ho Chi Minh City,<country>Vietnam</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff24">Academic Medical Center,<institution>University of Amsterdam</institution>
, 1012 WX Amsterdam,<country>The Netherlands</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Kuntaman, Kuntaman" sort="Kuntaman, Kuntaman" uniqKey="Kuntaman K" first="Kuntaman" last="Kuntaman">Kuntaman Kuntaman</name>
<affiliation><nlm:aff id="aff21">Department of Clinical Microbiology, Dr. Soetomo Academic Hospital – School of Medicine,<institution>Airlangga University</institution>
, Surabaya, Jawa Timur,<country>Indonesia</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Newton, Paul N" sort="Newton, Paul N" uniqKey="Newton P" first="Paul N." last="Newton">Paul N. Newton</name>
<affiliation><nlm:aff id="aff4">Nuffield Department of Clinical Medicine, Centre for Tropical Medicine,<institution>University of Oxford</institution>
, OX3 7BN Oxford,<country>United Kingdom</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff9">Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit, Microbiology Laboratory,<institution>Mahosot Hospital</institution>
, Vientiane,<country>Lao People’s Democratic Republic</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Moore, Catrin E" sort="Moore, Catrin E" uniqKey="Moore C" first="Catrin E." last="Moore">Catrin E. Moore</name>
<affiliation><nlm:aff id="aff4">Nuffield Department of Clinical Medicine, Centre for Tropical Medicine,<institution>University of Oxford</institution>
, OX3 7BN Oxford,<country>United Kingdom</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff9">Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit, Microbiology Laboratory,<institution>Mahosot Hospital</institution>
, Vientiane,<country>Lao People’s Democratic Republic</country>
;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Strugnell, Richard A" sort="Strugnell, Richard A" uniqKey="Strugnell R" first="Richard A." last="Strugnell">Richard A. Strugnell</name>
<affiliation><nlm:aff id="aff2">Department of Microbiology and Immunology,<institution>The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff16"><institution>Peter Doherty Institute, The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Thomson, Nicholas R" sort="Thomson, Nicholas R" uniqKey="Thomson N" first="Nicholas R." last="Thomson">Nicholas R. Thomson</name>
<affiliation><nlm:aff id="aff11">Pathogen Genomics,<institution>Wellcome Trust Sanger Centre</institution>
, CB10 1SA Cambridge,<country>United Kingdom</country>
;</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff25">Department of Pathogen Molecular Biology,<institution>The London School of Hygiene and Tropical Medicine</institution>
, WC1E 7HT London,<country>United Kingdom</country>
</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title>
<idno type="ISSN">0027-8424</idno>
<idno type="eISSN">1091-6490</idno>
<imprint><date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><title>Significance</title>
<p><italic>Klebsiella pneumoniae</italic>
is rapidly becoming untreatable using last-line antibiotics. It is especially problematic in hospitals, where it causes a range of acute infections. To approach controlling such a bacterium, we first must define what it is and how it varies genetically. Here we have determined the DNA sequence of <italic>K</italic>
. <italic>pneumoniae</italic>
isolates from around the world and present a detailed analysis of these data. We show that there is a wide spectrum of diversity, including variation within shared sequences and gain and loss of whole genes. Using this detailed blueprint, we show that there is an unrecognized association between the possession of specific gene profiles associated with virulence and antibiotic resistance and the differing disease outcomes seen for <italic>K</italic>
. <italic>pneumoniae</italic>
.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Proc Natl Acad Sci U S A</journal-id>
<journal-id journal-id-type="iso-abbrev">Proc. Natl. Acad. Sci. U.S.A</journal-id>
<journal-id journal-id-type="hwp">pnas</journal-id>
<journal-id journal-id-type="pmc">pnas</journal-id>
<journal-id journal-id-type="publisher-id">PNAS</journal-id>
<journal-title-group><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title>
</journal-title-group>
<issn pub-type="ppub">0027-8424</issn>
<issn pub-type="epub">1091-6490</issn>
<publisher><publisher-name>National Academy of Sciences</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">26100894</article-id>
<article-id pub-id-type="pmc">4500264</article-id>
<article-id pub-id-type="publisher-id">201501049</article-id>
<article-id pub-id-type="doi">10.1073/pnas.1501049112</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>PNAS Plus</subject>
</subj-group>
<subj-group subj-group-type="heading"><subject>Biological Sciences</subject>
<subj-group><subject>Microbiology</subject>
</subj-group>
</subj-group>
<series-title>PNAS Plus</series-title>
</article-categories>
<title-group><article-title>Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in <italic>Klebsiella pneumoniae</italic>
, an urgent threat to public health</article-title>
<alt-title alt-title-type="short"><italic>Klebsiella pneumoniae</italic>
, an urgent threat</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Holt</surname>
<given-names>Kathryn E.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wertheim</surname>
<given-names>Heiman</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>c</sup>
</xref>
<xref ref-type="aff" rid="aff4"><sup>d</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zadoks</surname>
<given-names>Ruth N.</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>e</sup>
</xref>
<xref ref-type="aff" rid="aff6"><sup>f</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Baker</surname>
<given-names>Stephen</given-names>
</name>
<xref ref-type="aff" rid="aff7"><sup>g</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Whitehouse</surname>
<given-names>Chris A.</given-names>
</name>
<xref ref-type="aff" rid="aff8"><sup>h</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Dance</surname>
<given-names>David</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>d</sup>
</xref>
<xref ref-type="aff" rid="aff9"><sup>i</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jenney</surname>
<given-names>Adam</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
<xref ref-type="aff" rid="aff10"><sup>j</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Connor</surname>
<given-names>Thomas R.</given-names>
</name>
<xref ref-type="aff" rid="aff11"><sup>k</sup>
</xref>
<xref ref-type="aff" rid="aff12"><sup>l</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hsu</surname>
<given-names>Li Yang</given-names>
</name>
<xref ref-type="aff" rid="aff13"><sup>m</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Severin</surname>
<given-names>Juliëtte</given-names>
</name>
<xref ref-type="aff" rid="aff14"><sup>n</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Brisse</surname>
<given-names>Sylvain</given-names>
</name>
<xref ref-type="aff" rid="aff15"><sup>o</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cao</surname>
<given-names>Hanwei</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
<xref ref-type="aff" rid="aff16"><sup>p</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wilksch</surname>
<given-names>Jonathan</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
<xref ref-type="aff" rid="aff16"><sup>p</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gorrie</surname>
<given-names>Claire</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
<xref ref-type="aff" rid="aff16"><sup>p</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Schultz</surname>
<given-names>Mark B.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Edwards</surname>
<given-names>David J.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Nguyen</surname>
<given-names>Kinh Van</given-names>
</name>
<xref ref-type="aff" rid="aff17"><sup>q</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Nguyen</surname>
<given-names>Trung Vu</given-names>
</name>
<xref ref-type="aff" rid="aff17"><sup>q</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Dao</surname>
<given-names>Trinh Tuyet</given-names>
</name>
<xref ref-type="aff" rid="aff17"><sup>q</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mensink</surname>
<given-names>Martijn</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>e</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Minh</surname>
<given-names>Vien Le</given-names>
</name>
<xref ref-type="aff" rid="aff7"><sup>g</sup>
</xref>
<xref ref-type="aff" rid="aff18"><sup>r</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Nhu</surname>
<given-names>Nguyen Thi Khanh</given-names>
</name>
<xref ref-type="aff" rid="aff7"><sup>g</sup>
</xref>
<xref ref-type="aff" rid="aff19"><sup>s</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Schultsz</surname>
<given-names>Constance</given-names>
</name>
<xref ref-type="aff" rid="aff7"><sup>g</sup>
</xref>
<xref ref-type="aff" rid="aff24"><sup>t</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kuntaman</surname>
<given-names>Kuntaman</given-names>
</name>
<xref ref-type="aff" rid="aff21"><sup>u</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Newton</surname>
<given-names>Paul N.</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>d</sup>
</xref>
<xref ref-type="aff" rid="aff9"><sup>i</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Moore</surname>
<given-names>Catrin E.</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>d</sup>
</xref>
<xref ref-type="aff" rid="aff9"><sup>i</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Strugnell</surname>
<given-names>Richard A.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
<xref ref-type="aff" rid="aff16"><sup>p</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Thomson</surname>
<given-names>Nicholas R.</given-names>
</name>
<xref ref-type="aff" rid="aff11"><sup>k</sup>
</xref>
<xref ref-type="aff" rid="aff25"><sup>v</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>1</sup>
</xref>
</contrib>
<aff id="aff1"><sup>a</sup>
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute,<institution>The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</aff>
<aff id="aff2"><sup>b</sup>
Department of Microbiology and Immunology,<institution>The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</aff>
<aff id="aff3"><sup>c</sup>
Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme,<institution>National Hospital for Tropical Diseases</institution>
, Hanoi,<institution>Vietnam</institution>
;</aff>
<aff id="aff4"><sup>d</sup>
Nuffield Department of Clinical Medicine, Centre for Tropical Medicine,<institution>University of Oxford</institution>
, OX3 7BN Oxford,<country>United Kingdom</country>
;</aff>
<aff id="aff5"><sup>e</sup>
Quality Milk Production Services,<institution>Cornell University</institution>
, Ithaca,<addr-line>NY</addr-line>
14853;</aff>
<aff id="aff6"><sup>f</sup>
Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences,<institution>University of Glasgow</institution>
, G12 8QQ Glasgow,<country>United Kingdom</country>
;</aff>
<aff id="aff7"><sup>g</sup>
The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme,<institution>Oxford University Clinical Research Unit</institution>
, Ho Chi Minh City,<country>Vietnam</country>
;</aff>
<aff id="aff8"><sup>h</sup>
<institution>United States Army Medical Research Institute of Infectious Diseases</institution>
, Fort Detrick,<addr-line>MD</addr-line>
21702;</aff>
<aff id="aff9"><sup>i</sup>
Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit, Microbiology Laboratory,<institution>Mahosot Hospital</institution>
, Vientiane,<country>Lao People’s Democratic Republic</country>
;</aff>
<aff id="aff10"><sup>j</sup>
Departmemt Infectious Diseases and Microbiology Unit,<institution>The Alfred Hospital</institution>
, Melbourne, VIC 3004, Australia;</aff>
<aff id="aff11"><sup>k</sup>
Pathogen Genomics,<institution>Wellcome Trust Sanger Centre</institution>
, CB10 1SA Cambridge,<country>United Kingdom</country>
;</aff>
<aff id="aff12"><sup>l</sup>
Cardiff University School of Biosciences,<institution>Cardiff University</institution>
, Cardiff, Wales, CF10 3AX,<country>United Kingdom</country>
;</aff>
<aff id="aff13"><sup>m</sup>
Department of Medicine,<institution>National University Health System</institution>
,<country>Singapore</country>
119228;</aff>
<aff id="aff14"><sup>n</sup>
Department of Medical Microbiology and Infectious Diseases,<institution>Erasmus University Medical Center</institution>
, 3015 CE Rotterdam,<country>The Netherlands</country>
;</aff>
<aff id="aff15"><sup>o</sup>
Microbial Evolutionary Genomics,<institution>Institut Pasteur</institution>
, CNRS, UMR3525, Paris,<country>France</country>
;</aff>
<aff id="aff16"><sup>p</sup>
<institution>Peter Doherty Institute, The University of Melbourne</institution>
, Parkville, VIC 3010, Australia;</aff>
<aff id="aff17"><sup>q</sup>
<institution>National Hospital for Tropical Diseases</institution>
, Hanoi,<country>Vietnam</country>
;</aff>
<aff id="aff18"><sup>r</sup>
Division of Infectious Diseases, Department of Medicine,<institution>University of California, San Francisco</institution>
,<addr-line>CA 94118-6215</addr-line>
;</aff>
<aff id="aff19"><sup>s</sup>
School of Chemistry and Molecular Biosciences,<institution>The University of Queensland</institution>
, Brisbane, QLD 4072,<country>Australia</country>
;</aff>
<aff id="aff24"><sup>t</sup>
Academic Medical Center,<institution>University of Amsterdam</institution>
, 1012 WX Amsterdam,<country>The Netherlands</country>
;</aff>
<aff id="aff21"><sup>u</sup>
Department of Clinical Microbiology, Dr. Soetomo Academic Hospital – School of Medicine,<institution>Airlangga University</institution>
, Surabaya, Jawa Timur,<country>Indonesia</country>
;</aff>
<aff id="aff25"><sup>v</sup>
Department of Pathogen Molecular Biology,<institution>The London School of Hygiene and Tropical Medicine</institution>
, WC1E 7HT London,<country>United Kingdom</country>
</aff>
</contrib-group>
<author-notes><corresp id="cor1"><sup>1</sup>
To whom correspondence may be addressed. Email: <email>nrt@sanger.ac.uk</email>
or <email>kholt@unimelb.edu.au</email>
.</corresp>
<fn fn-type="edited-by"><p>Edited by Simon A. Levin, Princeton University, Princeton, NJ, and approved May 11, 2015 (received for review January 16, 2015)</p>
</fn>
<fn fn-type="con"><p>Author contributions: K.E.H., H.W., R.A.S., and N.R.T. designed research; K.E.H. performed research; H.W., R.N.Z., S. Baker, C.A.W., D.D., A.J., L.Y.H., J.S., S. Brisse, H.C., J.W., K.V.N., T.V.N., T.T.D., M.M., V.L.M., N.T.K.N., C.S., K.K., P.N.N., and C.E.M. contributed new reagents/analytic tools; K.E.H., T.R.C., C.G., M.B.S., D.J.E., and N.R.T. analyzed data; and K.E.H. and N.R.T. wrote the paper.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><day>7</day>
<month>7</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="epub"><day>22</day>
<month>6</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>22</day>
<month>6</month>
<year>2015</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
. </pmc-comment>
<volume>112</volume>
<issue>27</issue>
<fpage>E3574</fpage>
<lpage>E3581</lpage>
<permissions><license license-type="open-access"><license-p>Freely available online through the PNAS open access option.</license-p>
</license>
</permissions>
<self-uri xlink:title="pdf" xlink:href="pnas.201501049.pdf"></self-uri>
<abstract abstract-type="executive-summary"><title>Significance</title>
<p><italic>Klebsiella pneumoniae</italic>
is rapidly becoming untreatable using last-line antibiotics. It is especially problematic in hospitals, where it causes a range of acute infections. To approach controlling such a bacterium, we first must define what it is and how it varies genetically. Here we have determined the DNA sequence of <italic>K</italic>
. <italic>pneumoniae</italic>
isolates from around the world and present a detailed analysis of these data. We show that there is a wide spectrum of diversity, including variation within shared sequences and gain and loss of whole genes. Using this detailed blueprint, we show that there is an unrecognized association between the possession of specific gene profiles associated with virulence and antibiotic resistance and the differing disease outcomes seen for <italic>K</italic>
. <italic>pneumoniae</italic>
.</p>
</abstract>
<abstract><p><italic>Klebsiella pneumoniae</italic>
is now recognized as an urgent threat to human health because of the emergence of multidrug-resistant strains associated with hospital outbreaks and hypervirulent strains associated with severe community-acquired infections. <italic>K</italic>
. <italic>pneumoniae</italic>
is ubiquitous in the environment and can colonize and infect both plants and animals. However, little is known about the population structure of <italic>K</italic>
. <italic>pneumoniae</italic>
, so it is difficult to recognize or understand the emergence of clinically important clones within this highly genetically diverse species. Here we present a detailed genomic framework for <italic>K</italic>
. <italic>pneumoniae</italic>
based on whole-genome sequencing of more than 300 human and animal isolates spanning four continents. Our data provide genome-wide support for the splitting of <italic>K</italic>
. <italic>pneumoniae</italic>
into three distinct species, KpI (<italic>K</italic>
. <italic>pneumoniae</italic>
), KpII (<italic>K</italic>
. <italic>quasipneumoniae</italic>
), and KpIII (<italic>K</italic>
. <italic>variicola</italic>
). Further, for <italic>K</italic>
. <italic>pneumoniae</italic>
(KpI), the entity most frequently associated with human infection, we show the existence of >150 deeply branching lineages including numerous multidrug-resistant or hypervirulent clones. We show <italic>K</italic>
. <italic>pneumoniae</italic>
has a large accessory genome approaching 30,000 protein-coding genes, including a number of virulence functions that are significantly associated with invasive community-acquired disease in humans. In our dataset, antimicrobial resistance genes were common among human carriage isolates and hospital-acquired infections, which generally lacked the genes associated with invasive disease. The convergence of virulence and resistance genes potentially could lead to the emergence of untreatable invasive <italic>K</italic>
. <italic>pneumoniae</italic>
infections; our data provide the whole-genome framework against which to track the emergence of such threats.</p>
</abstract>
<kwd-group><kwd><italic>Klebsiella pneumoniae</italic>
</kwd>
<kwd>genomics</kwd>
<kwd>virulence</kwd>
<kwd>antimicrobial resistance</kwd>
<kwd>population structure</kwd>
</kwd-group>
<funding-group><award-group id="gs1"><funding-source id="sp1">Department of Health, Australian Government | National Health and Medical Research Council (NHMRC)</funding-source>
<award-id rid="sp1">#628930</award-id>
</award-group>
<award-group id="gs2"><funding-source id="sp2">Department of Health, Australian Government | National Health and Medical Research Council (NHMRC)<named-content content-type="funder-id">501100000925</named-content>
</funding-source>
<award-id rid="sp2">#606788</award-id>
</award-group>
<award-group id="gs3"><funding-source id="sp3">Wellcome Trust<named-content content-type="funder-id">100004440</named-content>
</funding-source>
<award-id rid="sp3">#098051</award-id>
</award-group>
<award-group id="gs4"><funding-source id="sp4">Wellcome Trust<named-content content-type="funder-id">100004440</named-content>
</funding-source>
<award-id rid="sp4">#089275/H/09/Z</award-id>
</award-group>
<award-group id="gs5"><funding-source id="sp5">Victorian Life Sciences Computational Initiative</funding-source>
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