Establishment and evaluation of a BALBc mouse model of Burkholderia pseudomallei via nasal infection / 中国热带医学

ABSTRACT

@#Abstract Objective To establish an animal model of BALB/c mice infected with Burkholderia pseudomallei through the nose (inhalation route), provides a reliable animal model for the follow-up studies on the virulence of melioidosis and the pathogenesis of acute melioidosis. Methods　The experiment was carried out through infecting with Burkholderia pseudomallei through the nose (inhalation route). The pathophysiological response, visceral pathological damage and bacterial colonization of the mice infected with Burkholderia pseudomallei were observed by gross anatomy, histopathology and tissue homogenate count, and the biological characteristics of the mouse model of acute melioidosis were analyzed accordingly. Then we compared the physiological responses in BALB/c mice between the Burkholderia pseudomallei and non-pathogenic Burkholderia thailandensis. Results　In the model of acute nasal infection with Burkholderia thailandensis, most death happened between the 3rd to 5th day after infection, 3×105-3×106 CFU was the suitable dose for acute fatal melioidosis model of BALB/c mice, and the medium lethal dose was about 3×104-3×105 CFU. Both gross anatomy and tissue HE staining showed that abscesses or necrosis were found in the lung, spleen and liver, especially in the spleen and lung, which was positively correlated with the challenge dose. Viable bacteria was isolated from the blood, lung, spleen and liver of Burkholderia pseudomallei-infected mice, and the bacteria account colonization was related to tissue specificity. The concentration of live bacteria isolated from in the blood was the highest [Log2 value (10.28±0.34) CFU/mL], and the organ with the maximum quantity of bacteria was the lung [Log2 value (7.54±2.11) CFU/total organ]. It has been reported that the biological effects of Burkholderia pseudomallei and its homologous non-pathogenic Burkholderia thailandensis were similar at the cellular level, like multi-nuclear giant cell formation and active intracellular replication, while it is still unclarrified in the differences of virulence in mice. In this study, it was proved that Burkholderia thailandensis was not fatal to mice even at a high dose (8×107CFU), or detected from mice infected with it via nasal. Conclusion　We successfully established a reliable BALB/c mouse model (acute lethal model) of melioidosis via nasal infection, described its biological characteristics, and identified the different biological responses between Burkholderia pseudomallei and its homologous non-pathogenic Burkholderia thailandensis in mice.