Pathogenesis of Burkholderia mallei and pseudomallei

类鼻疽伯克霍尔德氏菌是一种革兰氏阴性、兼性厌氧、运动杆菌，可在人类和动物中观察到广泛的疾病。虽然流行病学调查表明，假鼻疽是赤道附近地区的地方病，但东南亚和澳大利亚北部的发病率尤其高。仅在泰国东北部，估计有20%的社区获得性败血症和大约40%的与细菌败血症相关的并发症死亡可归因于这种微生物。类鼻疽的表现通常表现为急性、亚急性和慢性病，临床表现常被误认为疟疾、鼠疫、肺炎和粟粒结核病。感染通常是通过吸入或吸入、摄入或通过受损表面组织与受污染的水或土壤直接接触而获得的。 马耳伯克霍尔德氏菌是一种革兰氏阴性细菌，是一种引起驴子、骡子、马，偶尔也会引起人类疾病的革兰氏阴性细菌。然而，与环境腐生假马利氏杆菌不同的是，马利氏杆菌在其单独寄主之外的自然界中并不存在。虽然马来杆菌和假鼻疽杆菌在基因上是相似的，但这两个致病物种之间确实存在显著的表型差异。虽然扁桃体是人类已知的最古老的疾病之一，但对由马来杆菌引起的疾病的发病机制知之甚少。这种现象主要是由于北美没有疾病，而且即使在受控的实验室环境中，研究马来杆菌也可能是一种特别危险的有机体。 众所周知，假鼻疽杆菌能抵抗活性氧和氮中间体的杀菌活性，并能在几种鼠和人巨噬细胞系中存活和繁殖(见电子显微镜)。为了确定与这些毒力表型相关的遗传位点，特别是那些在细胞内环境中上调或下调的基因，我们使用标准的巨噬细胞摄取实验，回收细胞内的细菌，并分离细菌的mRNA来探测DNA微阵列。从这些研究中获得的数据集被用来识别细胞内生存所需的基因。感兴趣的基因被等位基因交换打乱，其功能(S)通过两种活体模型系统(小鼠巨噬细胞侵袭，仓鼠感染性等)来定义。

Burkholderia pseudomallei, the etiological agent of melioidosis, is a Gram-negative, facultatively anaerobic, motile bacillus that is responsible for a broad spectrum of illnesses observed in both humans and animals. While epidemiological surveys have demonstrated that B. pseudomallei is endemic to regions that typically border the equator, the incidence of disease is particularly high in South-East Asia and Northern Australia. In north eastern Thailand alone, an estimated 20% of community acquired septicaemias and approximately 40% of deaths due to complications associated with bacterial sepsis can be attributed to this organism. The manifestations of melioidosis are commonly represented by acute, sub-acute and chronic illnesses, with the clinical manifestations often being mistaken for malaria, plague, pneumonia and miliary tuberculosis. Infections are typically acquired via inhalation or aspiration, ingestion or via the direct contact of damaged surface tissues with contaminated waters or soils. Burkholderia mallei, the etiological agent of glanders, is a Gram-negative bacterium that is responsible for disease in donkeys, mules, horses and occasionally humans. Unlike the environmental saprophyte B. pseudomallei, however, B. mallei does not persist in nature outside of its soliped hosts. While B. mallei and B. pseudomallei are genotypically similar, significant phenotypic differences do exist between the two pathogenic species. Although glanders is one of the oldest diseases known to man, relatively little is known about the pathogenesis of disease caused by B. mallei. This phenomenon is due primarily to the lack of disease in North America along with the fact that B. mallei can be a particularly dangerous organism to study even in a controlled laboratory environment. B. pseudomallei is known to resist the bactericidal activity of both reactive oxygen and nitrogen intermediates as well as to survive and multiply within several mouse and human macrophage cell lines (see electronmicrograph). In order to identify genetic loci associated with these virulence phenotypes, specifically those genes that are up or down-regulated in an intracellular environment, we use standard macrophage uptake assays, recover the intracellular bacteria and isolate bacterial mRNA to probe DNA micro-arrays. The data sets obtained from these studies are used to identify genes required for intracellular survival. Genes of interest are disrupted by allelic exchange and their function(s) are defined using both in vivo model systems (mouse macrophage invasion, infectivity in hamsters etc).