title: SitA contributes to the virulence of Klebsiella pneumoniae in a mouse infection model.
abstract: Klebsiella pneumoniae is an opportunistic pathogen, which causes a wide range of nosocomial infections. Recently, antibiotic resistance makes K. pneumoniae infection difficult to deal with. Investigation on virulence determinants of K. pneumoniae can provide more information about pathogenesis and unveil new targets for treatment or vaccine development. In this study, SitA, a Fur-regulated divalent cation transporter, was found significantly increased when K. pneumoniae was cultured in a nutrient-limited condition. A sitA-deletion strain (ΔsitA) was created to characterize the importance of SitA in virulence. ΔsitA showed higher sensitivity toward hydroperoxide than its parental strain. In a mouse intraperitoneal infection model, the survival rate of mice infected with ΔsitA strain increased greatly when compared with that of mice infected with the parental strain, suggesting that sitA deletion attenuates the bacterial virulence in vivo. To test whether ΔsitA strain is a potential vaccine candidate, mice were immunized with inactivated bacteria and then challenged with the wild-type strain. The results showed that using ΔsitA mutant protected mice better than using the wild-type strain or the capsule-negative congenic bacteria. In summary, SitA was found being important for the growth of K. pneumoniae in vivo and deleting sitA might be a potential approach to generate vaccines against K. pneumoniae.
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, 155 Sec. 2, Linong St., Beitou District, Taipei City 112, Taiwan, ROC; Taiwan International Graduate Program in Molecular Medicine, Academia Sinica, 128 Sec. 2, Academia Rd., Nankang, Taipei City 115, Taiwan, ROC.
authors.forename: Wei-Sheng W
authors.initials: WS
authors.lastname: Sun
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, 155 Sec. 2, Linong St., Beitou District, Taipei City 112, Taiwan, ROC; Taiwan International Graduate Program in Molecular Medicine, Academia Sinica, 128 Sec. 2, Academia Rd., Nankang, Taipei City 115, Taiwan, ROC.
authors.forename: Wan-Jr
authors.initials: WJ
authors.lastname: Syu
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, 155 Sec. 2, Linong St., Beitou District, Taipei City 112, Taiwan, ROC.
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Ho
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, 155 Sec. 2, Linong St., Beitou District, Taipei City 112, Taiwan, ROC.
authors.forename: Ching-Nan
authors.initials: CN
authors.lastname: Lin
authors.affiliation: Institute of Molecular and Genomic Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan, ROC.
authors.forename: Shih-Feng
authors.initials: SF
authors.lastname: Tsai
authors.affiliation: Department of Microbiology, Immunology and Biopharmaceuticals, National Chiayi University, 300 Syuefu Rd., Chiayi City 60004, Taiwan, ROC. Electronic address: shwang@mail.ncyu.edu.tw.
authors.forename: Shao-Hung
authors.initials: SH
authors.lastname: Wang
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D017353:Gene Deletion; D007710:Klebsiella Infections / Q000382:microbiology* / Q000473:pathology*; D007711:Klebsiella pneumoniae / Q000235:genetics / Q000472:pathogenicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D016019:Survival Analysis; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors
keywords: Klebsiella pneumoniae; Mouse intraperitoneal infection; SitA; Vaccination; Virulence determinant