title: Mutation in fucose synthesis gene of Klebsiella pneumoniae affects capsule composition and virulence in mice.
abstract: The emerging pathogenicity of Klebsiella pneumoniae (KP) is evident by the increasing number of clinical cases of liver abscess (LA) due to KP infection. A unique property of KP is its thick mucoid capsule. The bacterial capsule has been found to contain fucose in KP strains causing LA but not in those causing urinary tract infections. The products of the gmd and wcaG genes are responsible for converting mannose to fucose in KP. A KP strain, KpL1, which is known to have a high death rate in infected mice, was mutated by inserting an apramycin-resistance gene into the gmd. The mutant expressed genes upstream and downstream of gmd, but not gmd itself, as determined by reverse transcriptase polymerase chain reaction. The DNA mapping confirmed the disruption of the gmd gene. This mutant decreased its ability to kill infected mice and showed decreased virulence in infected HepG2 cells. Compared with wild-type KpL1, the gmd mutant lost fucose in capsular polysaccharides, increased biofilm formation and interacted more readily with macrophages. The mutant displayed morphological changes with long filament forms and less uniform sizes. The mutation also converted the serotype from K1 of wild-type to K2 and weak K3. The results indicate that disruption of the fucose synthesis gene affected the pathophysiology of this bacterium and may be related to the virulence of this KpL1 strain.
authors.affiliation: Department of Microbiology and Immunology and Institute of Biomedical Sciences, Chang Gung University, 259 Wen Hua 1st Road, Kwei San, Tao Yuan 333, Taiwan.
authors.forename: Po-Chang
authors.initials: PC
authors.lastname: Pan
authors.forename: Hui-Wen
authors.initials: HW
authors.lastname: Chen
authors.forename: Po-Kuan
authors.initials: PK
authors.lastname: Wu
authors.forename: Yu-Yang
authors.initials: YY
authors.lastname: Wu
authors.forename: Chun-Hung
authors.initials: CH
authors.lastname: Lin
authors.forename: June H
authors.initials: JH
authors.lastname: Wu
mesh_terms: D000818:Animals; D016667:Bacterial Capsules / Q000378:metabolism*; D053898:Biosynthetic Pathways / Q000235:genetics*; D002460:Cell Line; D004195:Disease Models, Animal; D005643:Fucose / Q000096:biosynthesis*; D055786:Gene Knockout Techniques; D022781:Hepatocytes / Q000382:microbiology; D006801:Humans; D006836:Hydro-Lyases / Q000235:genetics*; D007710:Klebsiella Infections / Q000382:microbiology / Q000473:pathology*; D007711:Klebsiella pneumoniae / Q000378:metabolism / Q000472:pathogenicity*; D008358:Mannose / Q000378:metabolism; D051379:Mice; D016254:Mutagenesis, Insertional; D017384:Sequence Deletion; D016019:Survival Analysis; D014774:Virulence
chemical_list: D005643:Fucose; C422948:GDP-D-mannose dehydratase, bacteria; D006836:Hydro-Lyases; D008358:Mannose