BALB/c and C57Bl/6 mice infected with virulent Burkholderia pseudomallei provide contrasting animal models for the acute and chronic forms of human melioidosis.
Burkholderia pseudomallei is the aetiological agent of melioidosis, a life-threatening bacterial disease occurring in many species of animals, including man. Infection in humans commonly manifests as one of three clinical presentations: acute, subacute or chronic disease. Investigations were undertaken to assess the suitability of BALB/c and C57Bl/6 mice as animal models for the different forms of human melioidosis. The course of infection in BALB/c mice was similar to that which occurs in acute human infection. By contrast, infection of C57Bl/6 mice appeared to mimic chronic human melioidosis. While BALB/c mice suffered a rapidly-progressive bacteraemia which resulted in host death by 96 h, C57Bl/6 mice were able to prevent this, and typically remained asymptomatic for up to 6 weeks. LD50 values of 4 cells and 2.5 x 10(4) cells for BALB/c and C57Bl/6 mice, respectively, reflect these observations. The heightened level of resistance to B. pseudomallei observed in C57Bl/6 mice was suggested to have a genetic basis, when the susceptibilities of first filial and reciprocal backcross generations were examined. Growth kinetics of B. pseudomallei within BALB/c and C57Bl/6 peritoneal exudate cell (PEC) cultures were examined to investigate PEC microbicidal efficiency as a determinant of host susceptibility. C57Bl/6 PEC cultures exhibited greater microbicidal efficiency towards B. pseudomallei when compared to BALB/c cells, indicating that susceptibility may be determined by non-specific, cellular mechanisms. Collectively, these results suggest that the BALB/c and C57Bl/6 strains of mice may provide excellent models for acute and chronic human melioidosis, respectively.
Leakey
A K
AK
Department of Microbiology and Immunology, James Cook University, Townsville, Australia.
Ulett
G C
GC
Hirst
R G
RG
D000818:Animals; D016957:Burkholderia pseudomallei / Q000472:pathogenicity*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007928:Lethal Dose 50; D008297:Male; D008554:Melioidosis / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C / Q000382:microbiology*; D008810:Mice, Inbred C57BL / Q000382:microbiology*