Characterization of a murine model of melioidosis: Comparison of differentstrains of mice

Melioidosis is an infectious disease caused by the saprophytic gram-negativ e rod Burkholderia pseudomallei. The aim of this study was to establish and characterize a murine model of melioidosis to provide a basis for further investigations on the pathogenesis of the disease. After intravenous infect ion with B. pseudomallei, C57BL/6 mice were found to be significantly more resistant than BALB/c mice. There was a marked organotropism of B. pseudoma llei for the spleen and liver in both strains of mice, with the highest bac terial load in the spleen. Electron microscopic investigations of the splee n clearly demonstrated intracellular replication within membrane-bound phag osomes. Electron micrographs of the liver provided evidence that B. pseudom allei-containing phagosomes in hepatocytes fuse with lysosomes, leading to degradation of bacteria. In both strains of mice, the course of infection w as highly dependent on the infective dose and the bacterial strain used, ra nging from death within a few days to death after several weeks. In compari son with BALB/c mice, the bacterial counts in C57BL/6 mice were decreased 1 2 h after infection, which is suggestive of an innate immune mechanism agai nst B. pseudomallei in this early phase of infection contributing to the lo wer susceptibility of C57BL/6 mice. BALB/c mice developed a more pronounced lymphopenia, granulocytosis, and splenomegaly at a lower infective dose co mpared to C57BL/6 mice. Analysis of the antibody response against B. pseudo mallei 11 days after infection revealed a significantly higher immunoglobul in G2A (IgG2a)/IgG1 ratio in C57BL/6 mice than in BALB/c mice, indicating t hat a T helper type 1 immune response is associated with resistance to infe ction with B. pseudomallei.