Ulett G C, Currie B J, Clair T W, Mayo M, Ketheesan N, Labrooy J, Gal D, Norton R, Smith C A, Barnes J, Warner J, Hirst R G
Department of Microbiology and Immunology, James Cook University, 4814, Townsville, Queensland, Australia.
Microbes Infect. 2001 Jul;3(8):621-31. doi: 10.1016/s1286-4579(01)01417-4.
Clinical presentations of melioidosis, caused by Burkholderia pseudomallei are protean, but the mechanisms underlying development of the different forms of disease remain poorly understood. In murine melioidosis, the level of virulence of B. pseudomallei is important in disease pathogenesis and progression. In this study, we used B. pseudomallei-susceptible BALB/c mice to determine the virulence of a library of clinical and environmental B. pseudomallei isolates from Australia and Papua New Guinea. Among 42 non-arabinose-assimilating (ara(-)) isolates, LD(50) ranged from 10 to > 10(6) CFU. There were numerous correlations between virulence and disease presentation in patients; however, this was not a consistent observation. Virulence did not correlate with isolate origin (i.e. clinical vs environmental), since numerous ara(-) environmental isolates were highly virulent. The least virulent isolate was a soil isolate from Papua New Guinea, which was arabinose assimilating (ara(+)). Stability of B. pseudomallei virulence was investigated by in vivo passage of isolates through mice and repetitive in vitro subculture. Virulence increased following in vivo exposure in only one of eight isolates tested. In vitro subculture on ferric citrate-containing medium caused attenuation of virulence, and this correlated with changes in colony morphology. Pulsed-field gel electrophoresis and randomly amplified polymorphic DNA typing demonstrated that selected epidemiologically related isolates that had variable clinical outcomes and different in vivo virulence were clonal strains. No molecular changes were observed in isolates after in vivo or in vitro exposure despite changes in virulence. These results indicate that virulence of selected B. pseudomallei isolates is variable, being dependent on factors such as iron bioavailability. They also support the importance of other variables such as inoculum size and host risk factors in determining the clinical severity of melioidosis.
由类鼻疽伯克霍尔德菌引起的类鼻疽临床表现多样，但不同疾病形式发展的潜在机制仍知之甚少。在鼠类类鼻疽中，类鼻疽伯克霍尔德菌的毒力水平在疾病发病机制和进展中很重要。在本研究中，我们使用对类鼻疽伯克霍尔德菌易感的BALB/c小鼠来测定来自澳大利亚和巴布亚新几内亚的临床和环境类鼻疽伯克霍尔德菌分离株文库的毒力。在42株非阿拉伯糖同化（ara(-)）分离株中，半数致死剂量（LD50）范围为10至>10^6 CFU。患者的毒力与疾病表现之间存在许多相关性；然而，这并非一致的观察结果。毒力与分离株来源（即临床分离株与环境分离株）无关，因为许多ara(-)环境分离株具有高毒力。毒力最低的分离株是来自巴布亚新几内亚的一株土壤分离株，它能同化阿拉伯糖（ara(+)）。通过将分离株在小鼠体内传代和重复体外传代培养来研究类鼻疽伯克霍尔德菌毒力的稳定性。在测试的八株分离株中，只有一株在体内暴露后毒力增加。在含柠檬酸铁的培养基上进行体外传代培养导致毒力减弱，这与菌落形态的变化相关。脉冲场凝胶电泳和随机扩增多态性DNA分型表明，选定的具有不同临床结果和不同体内毒力的流行病学相关分离株是克隆菌株。尽管毒力发生了变化，但在体内或体外暴露后分离株未观察到分子变化。这些结果表明，选定的类鼻疽伯克霍尔德菌分离株的毒力是可变的，取决于铁的生物可利用性等因素。它们还支持其他变量如接种量和宿主危险因素在决定类鼻疽临床严重程度方面的重要性。
