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Infection and Immunity, July 2009, p. 2657-2671, Vol. 77, No. 7
0019-9567/09/$08.00+0 doi:10.1128/IAI.01523-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Genetic Requirements for Klebsiella pneumoniae-Induced Liver Abscess in an Oral Infection Model
Ya-Chun Tu,1,
Min-Chi Lu,2,
Ming-Ko Chiang,3,
Shu-Ping Huang,1
Hwei-Ling Peng,4
Hwan-You Chang,5
Ming-Shiou Jan,1 and
Yi-Chyi Lai1*
Department of Microbiology and Immunology, Chung-Shan Medical University, Taichung,1 Institute of Medicine, Chung-Shan Medical University, Taichung,2 Department of Life Science, National Chung-Cheng University, Chia-Yi,3 Department of Biological Science and Technology, National Chiao-Tung University, Hsinchu,4 Institute of Molecular Medicine, National Tsing-Hua University, Hsinchu, Taiwan, Republic of China5
Received 15 December 2008/ Returned for modification 1 February 2009/ Accepted 28 April 2009
Klebsiella pneumoniae is the predominant pathogen of primary liver abscess. However, our knowledge regarding the molecular basis of how K. pneumoniae causes primary infection in the liver is limited. We established an oral infection model that recapitulated the characteristics of liver abscess and conducted a genetic screen to identify the K. pneumoniae genes required for the development of liver abscess in mice. Twenty-eight mutants with attenuated growth in liver or spleen samples out of 2,880 signature-tagged mutants that produced the wild-type capsule were identified, and genetic loci which were disrupted in these mutants were identified to encode products with roles in cellular metabolism, adhesion, transportation, gene regulation, and unknown functions. We further evaluated the virulence attenuation of these mutants in independent infection experiments and categorized them accordingly into three classes. In particular, the class I and II mutant strains exhibited significantly reduced virulence in mice, and most of these strains were not detected in extraintestinal tissues at 48 h after oral inoculation. Interestingly, the mutated loci of about one-third of the class I and II mutant strains encode proteins with regulatory functions, and the transcript abundances of many other genes identified in the same screen were markedly changed in these regulatory mutant strains, suggesting a requirement for genetic regulatory networks for translocation of K. pneumoniae across the intestinal barrier. Furthermore, our finding that preimmunization with certain class I mutant strains protected mice against challenge with the wild-type strain implied a potential application for these strains in prophylaxis against K. pneumoniae infections.
* Corresponding author. Mailing address: Department of Microbiology and Immunology, Chung-Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, Taichung 402, Taiwan, Republic of China. Phone: 886-4-24730022-11631. Fax: 886-4-24727178. E-mail: yclai{at}csmu.edu.tw
Published ahead of print on 11 May 2009.
These authors contributed equally to this work.
Infection and Immunity, July 2009, p. 2657-2671, Vol. 77, No. 7
0019-9567/09/$08.00+0 doi:10.1128/IAI.01523-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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