The human pathogen Pseudomonas aeruginosa utilizes conserved virulence pathways to infect the social amoeba Dictyostelium discoideum
The human pathogen Pseudomonas aeruginosa utilizes conserved virulence pathways to infect the social amoeba Dictyostelium discoideum
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DOI：
10.1073/pnas.052704399
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发表时间：
2002-03-05
影响因子：
11.1
通讯作者：
Mekalanos, JJ
中科院分区：
文献类型：
--
作者：
Pukatzki, S;Kessin, RH;Mekalanos, JJ
遗传可及宿主模型对于研究微生物发病机制是有用的，因为它们提供了确定病原体用来逃避免疫机制、引起细胞损伤和诱发疾病的新策略的手段。我们已经开发条件下，人类病原体铜绿假单胞菌感染盘状盘基钢，一种遗传易感真核生物。当盘状假单胞菌被镀在不同铜绿假单胞菌菌株的营养琼脂板上时，细菌在这些板上形成草坪，其中嵌入变形虫。毒力强的铜绿假单胞菌菌株杀死这些变形虫，留下完整的细菌草坪。许多铜绿假单胞菌突变体已经确定，在这个试验是无毒的。变形虫以这些细菌为食，在它们的细菌草坪上形成斑块。一种无毒突变株携带lasR基因的插入突变。LasR是一种转录因子，以密度依赖的方式控制许多毒力基因。另一类无毒的铜绿假单胞菌突变体在III型分泌上有缺陷。其中一个突变体缺乏分泌器官的结构成分PscJ蛋白，这表明细胞毒素被注射到盘状蝶细胞中。其中一种细胞毒素是ExoU，而ExoU突变体对盘状棘球蚴是无毒的。IasR和exoU突变的互补恢复了毒力。因此，铜绿假单胞菌使用保守的毒力途径杀死盘状假单胞菌。
Genetically accessible host models are useful for studying microbial pathogenesis because they offer the means to identify novel strategies that pathogens use to evade immune mechanisms, cause cellular injury, and induce disease. We have developed conditions under which the human pathogen Pseudomonas aeruginosa infects Dictyostelium discoideum, a genetically tractable eukaryotic organism. When D. discoideum is plated on nutrient agar plates with different P. aeruginosa strains, the bacteria form lawns on these plates with amoebae embedded in them. Virulent P. aeruginosa strains kill these amoebae and leave an intact bacterial lawn. A number of P. aeruginosa mutants have been identified that are avirulent in this assay. Amoebae feed on these bacteria and form plaques in their bacterial lawns. One avirulent mutant strain carries an insertional mutation in the lasR gene. LasR is a transcription factor that controls a, number of virulence genes in a density dependent fashion. Another class of avirulent P. aeruginosa mutants is defective in type III secretion. One mutant lacks the PscJ protein, a structural component of the secretion apparatus, suggesting that cytotoxins are injected into the D. discoideum cell. One of these cytotoxins is ExoU, and exoU mutants are avirulent toward D. discoideum. Complementation of the IasR and exoU mutations restores virulence. Therefore, A aeruginosa uses conserved virulence pathways to kill D. discoideum.