Genotoxic Klebsiella pneumoniae in Taiwan.
BACKGROUND
Colibactin is a nonribosomal peptide-polyketide synthesized by multi-enzyme complexes encoded by the pks gene cluster. Colibactin-producing Escherichia coli have been demonstrated to induce host DNA damage and promote colorectal cancer (CRC) development. In Taiwan, the occurrence of pyogenic liver abscess (PLA) has been suggested to correlate with an increasing risk of CRC, and Klebsiella pneumoniae is the predominant PLA pathogen in Taiwan.


RESULTS
At the asn tRNA loci of the newly sequenced K. pneumoniae 1084 genome, we identified a 208-kb genomic island, KPHPI208, of which a module identical to the E. coli pks colibactin gene cluster was recognized. KPHPI208 consists of eight modules, including the colibactin module and the modules predicted to be involved in integration, conjugation, yersiniabactin production, microcin production, and unknown functions. Transient infection of BALB/c normal liver cells with K. pneumoniae 1084 increased the phosphorylation of histone H2AX, indicating the induction of host DNA damage. Colibactin was required for the genotoxicity of K. pneumoniae 1084, as it was diminished by deletion of clbA gene and restored to the wild type level by trans-complementation with a clbA coding plasmid. Besides, BALB/c mice infected with K. pneumoniae 1084 exhibited enhanced DNA damage in the liver parenchymal cells when compared to the isogenic clbA deletion mutant. By PCR detection, the prevalence of pks-positive K. pneumoniae in Taiwan is 25.6%, which is higher than that reported in Europe (3.5%), and is significantly correlated with K1 type, which predominantly accounted for PLA in Taiwan.


CONCLUSIONS
Our knowledge regarding how bacteria contribute to carcinogenesis has just begun. The identification of genotoxic K. pneumoniae and its genetic components will facilitate future studies to elucidate the molecular basis underlying the link between K. pneumoniae, PLA, and CRC.
Department of Microbiology and Immunology, Chung-Shan Medical University, Taichung City, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, Chung-Shan Medical University Hospital, Taichung City, Taiwan; Institute of Microbiology and Immunology, Chung-Shan Medical University, Taichung City, Taiwan.
Yi-Chyi
YC
Lai
Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli County, Taiwan.
Ann-Chi
AC
Lin
Department of Life Science, National Chung Cheng University, Chia-Yi County, Taiwan.
Ming-Ko
MK
Chiang
Institute of Microbiology and Immunology, Chung-Shan Medical University, Taichung City, Taiwan.
Yu-Han
YH
Dai
Institute of Microbiology and Immunology, Chung-Shan Medical University, Taichung City, Taiwan.
Chih-Chieh
CC
Hsu
Department of Microbiology and Immunology, Chung-Shan Medical University, Taichung City, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, Chung-Shan Medical University Hospital, Taichung City, Taiwan; Institute of Microbiology and Immunology, Chung-Shan Medical University, Taichung City, Taiwan.
Min-Chi
MC
Lu
Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung City, Taiwan.
Chun-Yi
CY
Liau
Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli County, Taiwan; Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung City, Taiwan; Biotechnology Center, National Chung Hsing University, Taichung City, Taiwan.
Ying-Tsong
YT
Chen
D000818:Animals; D002460:Cell Line; D004249:DNA Damage; D017353:Gene Deletion; D005798:Genes, Bacterial; D006801:Humans; D007710:Klebsiella Infections / Q000150:complications* / Q000453:epidemiology / Q000235:genetics / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000235:genetics* / Q000502:physiology; D008099:Liver / Q000382:microbiology; D046290:Liver Abscess, Pyogenic / Q000209:etiology / Q000235:genetics / Q000382:microbiology; D008807:Mice, Inbred BALB C; D005810:Multigene Family; D009153:Mutagens / Q000378:metabolism*; D010455:Peptides / Q000235:genetics*; D061065:Polyketides; D013624:Taiwan / Q000453:epidemiology
D009153:Mutagens; D010455:Peptides; D061065:Polyketides; C569566:colibactin