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Journal of Bacteriology, July 2009, p. 4492-4501, Vol. 191, No. 14
0021-9193/09/$08.00+0     doi:10.1128/JB.00315-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Genome Sequencing and Comparative Analysis of Klebsiella pneumoniae NTUH-K2044, a Strain Causing Liver Abscess and Meningitis {triangledown} ,{dagger}

Keh-Ming Wu,1,2 Ling-Hui Li,2,{ddagger} Jing-Jou Yan,3 Nina Tsao,4,5 Tsai-Lien Liao,2 Hui-Chi Tsai,6,§ Chang-Phone Fung,7 Hsiang-Ju Chen,2 Yen-Ming Liu,2 Jin-Tung Wang,8 Chi-Tai Fang,8 Shan-Chwen Chang,8 Hung-Yu Shu,6,¶ Tze-Tze Liu,6 Ying-Tsong Chen,2 Yih-Ru Shiau,4 Tsai-Ling Lauderdale,4 Ih-Jen Su,4 Ralph Kirby,9* and Shih-Feng Tsai1,2,6,9*

Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan,1 Division of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Miaoli, Taiwan,2 Department of Pathology, National Cheng Kung University Hospital, Tainan, Taiwan,3 Division of Clinical Research, National Health Research Institutes, Zhunan, Miaoli, Taiwan,4 Department of Biological Science and Technology, I-Shou University, Kaohsiung County, Taiwan,5 Genome Research Center, National Yang-Ming University, Taipei, Taiwan,6 Faculty of Medicine, School of Medicine, National Yang-Ming University and Taipei Veterans General Hospital, Taipei, Taiwan,7 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan,8 Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan9

Received 8 March 2009/ Accepted 6 May 2009

Nosocomial infections caused by antibiotic-resistant Klebsiella pneumoniae are emerging as a major health problem worldwide, while community-acquired K. pneumoniae infections present with a range of diverse clinical pictures in different geographic areas. In particular, an invasive form of K. pneumoniae that causes liver abscesses was first observed in Asia and then was found worldwide. We are interested in how differences in gene content of the same species result in different diseases. Thus, we sequenced the whole genome of K. pneumoniae NTUH-K2044, which was isolated from a patient with liver abscess and meningitis, and analyzed differences compared to strain MGH 78578, which was isolated from a patient with pneumonia. Six major types of differences were found in gene clusters that included an integrative and conjugative element, clusters involved in citrate fermentation, lipopolysaccharide synthesis, and capsular polysaccharide synthesis, phage-related insertions, and a cluster containing fimbria-related genes. We also conducted comparative genomic hybridization with 15 K. pneumoniae isolates obtained from community-acquired or nosocomial infections using tiling probes for the NTUH-K2044 genome. Hierarchical clustering revealed three major groups of genomic insertion-deletion patterns that correlate with the strains' clinical features, antimicrobial susceptibilities, and virulence phenotypes with mice. Here we report the whole-genome sequence of K. pneumoniae NTUH-K2044 and describe evidence showing significant genomic diversity and sequence acquisition among K. pneumoniae pathogenic strains. Our findings support the hypothesis that these factors are responsible for the changes that have occurred in the disease profile over time.

* Corresponding author. Mailing address for Ralph Kirby: Department of Life Sciences & Institute of Genome Sciences, National Yang-Ming University, 155 Li-Nong St., Section 2, Bei-Tou, Taipei 112, Taiwan. Phone: 886-2-28267323. Fax: 886-2-28202449. E-mail: rkirby{at}ym.edu.tw. Mailing address for Shih-Feng Tsai: Division of Molecular and Genomic Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli 350, Taiwan. Phone: 886-37-246166, ext. 35300. Fax: 886-37-586459. E-mail: petsai{at}nhri.org.tw

{triangledown} Published ahead of print on 15 May 2009.

{dagger} Supplemental material for this article may be found at http://jb.asm.org/.

{ddagger} Present address: National Genotyping Center at Academia Sinica, Institute of Biomedical Sciences, 128 Academia Road, Section 2, Nangang District, Taipei 115, Taiwan.

§ Present address: UC Davis Cancer Center Basic Science, UC Davis Medical Center, Research III, 4645 2nd Avenue, Sacramento, CA 95817.

Present address: Department of BioScience Technology, Chang Jung Christian University, Kway Jen, Tainan 71101, Taiwan.

Journal of Bacteriology, July 2009, p. 4492-4501, Vol. 191, No. 14
0021-9193/09/$08.00+0     doi:10.1128/JB.00315-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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