Haraga Andrea, West T Eoin, Brittnacher Mitchell J, Skerrett Shawn J, Miller Samuel I
Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Infect Immun. 2008 Nov;76(11):5402-11. doi: 10.1128/IAI.00626-08. Epub 2008 Sep 8.
Burkholderia pseudomallei is a bacterial pathogen that causes a broad spectrum of clinical symptoms collectively known as melioidosis. Since it can be acquired by inhalation and is difficult to eradicate due to its resistance to a wide group of antibiotics and capacity for latency, work with B. pseudomallei requires a biosafety level 3 (BSL-3) containment facility. The bsa (Burkholderia secretion apparatus)-encoded type III secretion system (TTSS) has been shown to be required for its full virulence in a number of animal models. TTSSs are export devices found in a variety of gram-negative bacteria that translocate bacterial effector proteins across host cell membranes into the cytoplasm of host cells. Although the Bsa TTSS has been shown to play an important role in the ability of B. pseudomallei to survive and replicate in mammalian cells, escape from the endocytic vacuole, and spread from cell to cell, little is known about its effectors mediating these functions. Using bioinformatics, we identified homologs of several known TTSS effectors from other bacteria in the B. pseudomallei genome. In addition, we show that orthologs of these putative effectors exist in the genome of B. thailandensis, a closely related bacterium that is rarely pathogenic to humans. By generating a Bsa TTSS mutant B. thailandensis strain, we also demonstrated that the Bsa TTSS has similar functions in the two species. Therefore, we propose B. thailandensis as a useful BSL-1 model system to study the role of the Bsa TTSS during Burkholderia infection of mammalian cells and animals.
类鼻疽伯克霍尔德菌是一种细菌病原体，可引发一系列统称为类鼻疽的临床症状。由于它可通过吸入感染，且对多种抗生素具有抗性并具备潜伏能力，难以根除，因此处理类鼻疽伯克霍尔德菌需要生物安全3级（BSL-3）防护设施。已证明由bsa（伯克霍尔德菌分泌装置）编码的III型分泌系统（TTSS）在多种动物模型中对其完全毒力是必需的。TTSS是在多种革兰氏阴性细菌中发现的输出装置，可将细菌效应蛋白穿过宿主细胞膜转运到宿主细胞的细胞质中。尽管已证明Bsa TTSS在类鼻疽伯克霍尔德菌在哺乳动物细胞中存活和复制、从内吞泡逃逸以及在细胞间传播的能力中发挥重要作用，但其介导这些功能的效应蛋白却知之甚少。利用生物信息学，我们在类鼻疽伯克霍尔德菌基因组中鉴定出了几种来自其他细菌的已知TTSS效应蛋白的同源物。此外，我们表明这些假定效应蛋白的直系同源物存在于泰国伯克霍尔德菌的基因组中，泰国伯克霍尔德菌是一种与类鼻疽伯克霍尔德菌密切相关但很少对人类致病的细菌。通过构建一株Bsa TTSS突变的泰国伯克霍尔德菌菌株，我们还证明了Bsa TTSS在这两个物种中具有相似的功能。因此，我们提出将泰国伯克霍尔德菌作为一种有用的BSL-1模型系统，用于研究Bsa TTSS在伯克霍尔德菌感染哺乳动物细胞和动物过程中的作用。
