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.
Highlights
Burkholderia mallei, the causative agent of glanders, is a Gram-negative, aerobic bacillus
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
Chemical composition of O-antigens varies among different bacterial species, as a result of the genetic variation in the genes involved in O-antigen biosynthesis, designated the wb cluster
Summary
Burkholderia mallei, the causative agent of glanders, is a Gram-negative, aerobic bacillus. This bacterium is primarily responsible for disease in horses, mules, donkeys and occasionally humans [1,2,3]. In gram-negative bacteria, lipopolysaccharides (LPS), commonly referred to as endotoxins, are a major component of cell envelopes [6,7]. Chemical composition of O-antigens varies among different bacterial species, as a result of the genetic variation in the genes involved in O-antigen biosynthesis, designated the wb cluster. Burtnick et al [12] identified the gene cluster responsible for O-antigen biosynthesis in B. mallei ATCC 23344, and determined the physical structure of the B. mallei ATCC 23344 O-antigen
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