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M. R. Burns, S. A. Jenkins, S. J. Wood, K. Miller and S. A. David, “Structure-Activity Relationships in Lipopolysaccharide Neutralizers: Design, Synthesis, and Biological Evaluation of a 540-Membered Amphipathic Bisamide Library,” Journal of Combinatorial Chemistry, Vol. 8, No. 1, 2006, pp. 32-43. doi:10.1021/cc0500755

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• TITLE: A wzt Mutant Burkholderia mallei Is Attenuated and Partially Protects CD1 Mice against Glanders

  AUTHORS: Aloka B. Bandara

  KEYWORDS: Burkholderia mallei; ABC-2 Transporter; wzm Integral Membrane Protein; wzm Hydrophilic ATP-Binding Protein; Glanders; CD1 Mice; Pathogenicity; Protection

  JOURNAL NAME: Advances in Infectious Diseases, Vol.2 No.3, September 27, 2012

  ABSTRACT: Burkholderia mallei is the etiologic agent of glanders in solipeds and humans. Lipopolysaccharide (LPS) is a major component of cell envelop of this pathogen. O-antigen, the most external component of LPS, is a virulence factor and a protective antigen in many pathogenic bacteria. Two putative proteins named Wzm (integral membrane protein) and Wzt (hydrophilic ATP-binding protein) are believed to make up an ABC-2 transporter of B. mallei that facilitates transport of components of O-antigen from cytosol to outer-membrane. We studied the importance of wzt (encoding Wzt) to growth, LPS O-antigen profile, and pathogenicity of B. mallei. A wzt mutant strain was generated by deleting a portion of the wzt in B. mallei wild type strain ATCC 23344 by gene replacement. Compared to the wild type strain, the wzt mutant displayed slower growth in vitro and less lethality in CD1 mice when inoculated intraperitoneally. The 50% lethal doses (LD50) of the wild type and the wzt mutant strains were 5.9 × 105 and 9.1 × 105 cfu, respectively. CD1 mice inoculated with a non-lethal dose of the wzt mutant produced specific serum immunoglobulins IgG1 and IgG2a and were partially protected against challenge with 11.2 times LD50 of the wild type strain. These findings suggest that the wzt is required for optimal in vitro growth and pathogenesis of B. mallei, and a wzt mutant protects CD1 mice against glanders.