Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in <i>Klebsiella pneumoniae</i> , an urgent threat to public health

Proceedings of the National Academy of Sciences of the United States of America - Tập 112 Số 27 - 2015
Kathryn E. Holt1,2, Heiman Wertheim3,4, Ruth N. Zadoks5,6, Stephen Baker7, Chris A. Whitehouse8, David A. B. Dance9,3, Adam Jenney10,11, Thomas R. Connor12,13, Li Yang Hsu14, Juliëtte A. Severin15, Sylvain Brisse16, Hanwei Cao17,18, Jonathan J. Wilksch2,18, Claire L. Gorrie1,2,18, Mark B. Schultz1, David J. Edwards19, Kinh Van Nguyen20, Trung Vu Nguyen21, Trinh Tuyet Dao21, Martijn Mensink22, Vien Le Minh23,7, Nguyen Thi Khanh Nhu24,7, Constance Schultsz25,26, Kuntaman Kuntaman27, Paul N. Newton9,28, Catrin E. Moore9,28, Richard A. Strugnell2,18, Nicholas R. Thomson29,30
1Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3010, Australia
2Department of Microbiology and Immunology, The University of Melbourne, Parkville, VIC, 3010, Australia
3Nuffield Department of Clinical Medicine, Centre for Tropical Medicine, University of Oxford, OX3 7BN Oxford, United Kingdom;
4Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, National Hospital for Tropical Diseases, Hanoi, Vietnam;
5Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, G12 8QQ Glasgow, United Kingdom;
6Quality Milk Production Services, Cornell University, Ithaca, NY 14853; Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, G12 8QQ Glasgow, United Kingdom;
7The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University, Clinical Research Unit, Ho Chi Minh City, Vietnam
8United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702;
9Lao-Oxford-Mahosot Hospital Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao People’s Democratic Republic;
10Departmemt Infectious Diseases and Microbiology Unit, The Alfred Hospital, Melbourne, VIC 3004, Australia;
11Department of Microbiology and Immunology, The University of Melbourne, Parkville, VIC 3010, Australia; Departmemt Infectious Diseases and Microbiology Unit, The Alfred Hospital, Melbourne, VIC 3004, Australia;
12Cardiff University School of Biosciences, Cardiff University, Cardiff, Wales, CF10 3AX, United Kingdom;
13Pathogen Genomics, Wellcome Trust Sanger Centre, CB10 1SA Cambridge, United Kingdom; Cardiff University School of Biosciences, Cardiff University, Cardiff, Wales, CF10 3AX, United Kingdom;
14Department of Medicine, National University Health System, Singapore 119228;
15Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, 3015 CE Rotterdam, The Netherlands;
16Microbial Evolutionary Genomics, Institut Pasteur, CNRS, UMR3525, Paris, France
17Department of Microbiology and Immunology, The University of Melbourne, Parkville, VIC 3010, Australia; Peter Doherty Institute, The University of Melbourne, Parkville, VIC 3010, Australia;
18Peter Doherty Institute, The University of Melbourne, Parkville, VIC 3010, Australia;
19aDepartment of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3010, Australia;
20National Hospital for Tropical Diseases, Hanoi, Vietnam
21qNational Hospital for Tropical Diseases, Hanoi, Vietnam;
22Quality Milk Production Services, Cornell University, Ithaca, NY 14853
23Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, CA 94118-6215;
24School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia
25Academic Medical Center, University of Amsterdam, 1012 WX Amsterdam, The Netherlands;
26The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam; Academic Medical Center, University of Amsterdam, 1012 WX Amsterdam, The Netherlands;
27Department of Clinical Microbiology, Dr. Soetomo Academic Hospital - School of Medicine, Airlangga University, Surabaya, Jawa Timur, Indonesia;
28dNuffield Department of Clinical Medicine, Centre for Tropical Medicine, University of Oxford, OX3 7BN Oxford, United Kingdom;
29kPathogen Genomics, Wellcome Trust Sanger Centre, CB10 1SA Cambridge, United Kingdom;
30vDepartment of Pathogen Molecular Biology, The London School of Hygiene and Tropical Medicine, WC1E 7HT London, United Kingdom

Tóm tắt

Significance Klebsiella pneumoniae 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 K . pneumoniae 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 K . pneumoniae .

Từ khóa


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Proceedings of the National Academy of Sciences of the United States of America

Tập 112 Số 27

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