Genetic requirements for Klebsiella pneumoniae-induced liver abscess in an oral infection model.
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.
Department of Microbiology and Immunology, Chung-Shan Medical University, Taichung 402, Taiwan, Republic of China.
Ya-Chun
YC
Tu
Min-Chi
MC
Lu
Ming-Ko
MK
Chiang
Shu-Ping
SP
Huang
Hwei-Ling
HL
Peng
Hwan-You
HY
Chang
Ming-Shiou
MS
Jan
Yi-Chyi
YC
Lai
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D001428:Bacterial Vaccines / Q000276:immunology; D004251:DNA Transposable Elements; D020869:Gene Expression Profiling; D055786:Gene Knockout Techniques; D006801:Humans; D007710:Klebsiella Infections / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000235:genetics* / Q000472:pathogenicity*; D008100:Liver Abscess / Q000382:microbiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016254:Mutagenesis, Insertional; D014613:Vaccines, Attenuated / Q000276:immunology; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics
D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D004251:DNA Transposable Elements; D014613:Vaccines, Attenuated; D037521:Virulence Factors