Wiersinga W Joost, de Vos Alex F, de Beer Regina, Wieland Catharina W, Roelofs Joris J T H, Woods Donald E, van der Poll Tom
Center for Infection and Immunity Amsterdam (CINIMA), Amsterdam, The Netherlands.
Cell Microbiol. 2008 Jan;10(1):81-7. doi: 10.1111/j.1462-5822.2007.01016.x. Epub 2007 Jul 20.
Burkholderia pseudomallei, which causes melioidosis, a severe, mainly pulmonary disease endemic in South-East Asia, is considered to be the most pathogenic of the Burkholderia genus. B. thailandensis, however, is considered avirulent. We determined differences in patterns of inflammation of B. pseudomallei 1026b (clinical virulent isolate), B. pseudomallei AJ1D8 (an in vitro invasion-deficient mutant generated from strain 1026b by Tn5-OT182 mutagenesis) and B. thailandensis by intranasally inoculating C57BL/6 mice with each strain. Mice infected with B. thailandensis showed a markedly decreased bacterial outgrowth from lungs, spleen and blood 24 h after inoculation, compared with infection with B. pseudomallei and the invasion mutant AJ1D8. Forty-eight hours after inoculation, B. thailandensis was no longer detectable. This was consistent with elevated pulmonary cytokine and chemokine concentrations after infection with B. pseudomallei 1026b and AJ1D8, and the absence of these mediators 48 h, but not 24 h, after inoculation with B. thailandensis. Histological examination, however, did show marked pulmonary inflammation in the mice infected with B. thailandensis, corresponding with substantial granulocyte influx and raised myeloperoxidase levels. Survival experiments showed that infection with 1 x 10(3) cfu B. thailandensis was not lethal, whereas inoculation with 1 x 10(6) cfu B. thailandensis was equally lethal as 1 x 10(3) cfu B. pseudomallei 1026b or AJ1D8. These data show that B. pseudomallei AJ1D8 is just as lethal as wild-type B. pseudomallei in an in vivo mouse model, and B. thailandensis is perhaps more virulent than is often recognized.
类鼻疽伯克霍尔德菌可引发类鼻疽,这是一种主要在东南亚流行的严重肺部疾病,该菌被认为是伯克霍尔德菌属中致病性最强的。然而,泰国伯克霍尔德菌被认为无致病性。我们通过给C57BL/6小鼠经鼻接种类鼻疽伯克霍尔德菌1026b(临床致病分离株)、类鼻疽伯克霍尔德菌AJ1D8(由1026b菌株经Tn5 - OT182诱变产生的体外侵袭缺陷型突变体)和泰国伯克霍尔德菌,来确定这三种菌株在炎症模式上的差异。与感染类鼻疽伯克霍尔德菌和侵袭突变体AJ1D8相比,感染泰国伯克霍尔德菌的小鼠在接种后24小时,肺、脾和血液中的细菌生长显著减少。接种48小时后,已检测不到泰国伯克霍尔德菌。这与感染类鼻疽伯克霍尔德菌1026b和AJ1D8后肺细胞因子和趋化因子浓度升高一致,而接种泰国伯克霍尔德菌48小时后(而非24小时后)则没有这些介质。然而,组织学检查确实显示感染泰国伯克霍尔德菌的小鼠肺部有明显炎症,伴有大量粒细胞流入和髓过氧化物酶水平升高。生存实验表明,感染1×10³ cfu泰国伯克霍尔德菌不会致死,而接种1×10⁶ cfu泰国伯克霍尔德菌的致死率与接种1×10³ cfu类鼻疽伯克霍尔德菌1026b或AJ1D8相同。这些数据表明,在体内小鼠模型中,类鼻疽伯克霍尔德菌AJ1D8与野生型类鼻疽伯克霍尔德菌一样具有致死性,并且泰国伯克霍尔德菌的毒性可能比通常认为的更强。