Genome-wide analysis reveals loci encoding anti-macrophage factors in the human pathogen Burkholderia pseudomallei K96243.
Genome-wide analysis reveals loci encoding anti-macrophage factors in the human pathogen Burkholderia pseudomallei K96243.
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DOI：
10.1371/journal.pone.0015693
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发表时间：
2010-12-22
期刊：
影响因子：
3.7
通讯作者：
Ffrench-Constant RH
中科院分区：
文献类型：
--
作者：
Dowling AJ;Wilkinson PA;Holden MT;Quail MA;Bentley SD;Reger J;Waterfield NR;Titball RW;Ffrench-Constant RH
假玛利伯克氏菌是一种重要的人类病原体，其感染生物学尚不清楚。这种细菌是热带地区的地方病，包括东南亚和北澳大利亚，它在那里引起类鼻疽病，这是一种与高死亡率和抗生素耐药性相关的严重疾病。假芽孢杆菌是一种革兰氏阴性兼性细胞内病原体，能够在巨噬细胞中复制。然而，尽管其与巨噬细胞相互作用的关键性质，迄今为止很少有抗巨噬细胞因子被表征。本研究对假芽孢杆菌菌株K96243进行全基因组功能筛选，以鉴定具有抗巨噬细胞活性的基因座编码因子。我们共鉴定出113个这样的位点，分布在两条染色体上，阳性基因簇编码转运体和分泌系统、酶/毒素、次生代谢物、生物膜、粘附和信号响应相关因素。对其中四个区域的进一步表型分析表明，编码因子引起与感染生物学相关的显著细胞表型，包括细胞凋亡、肌动蛋白“尾”的形成和处理后巨噬细胞内的多核。对剩余宿主基因座的详细分析将有助于对这一重要病原体与宿主巨噬细胞相互作用的遗传学解剖，从而进一步阐明其感染周期的这一关键部分。
Burkholderia pseudomallei is an important human pathogen whose infection biology is still poorly understood. The bacterium is endemic to tropical regions, including South East Asia and Northern Australia, where it causes melioidosis, a serious disease associated with both high mortality and antibiotic resistance. B. pseudomallei is a Gram-negative facultative intracellular pathogen that is able to replicate in macrophages. However despite the critical nature of its interaction with macrophages, few anti-macrophage factors have been characterized to date. Here we perform a genome-wide gain of function screen of B. pseudomallei strain K96243 to identify loci encoding factors with anti-macrophage activity. We identify a total of 113 such loci scattered across both chromosomes, with positive gene clusters encoding transporters and secretion systems, enzymes/toxins, secondary metabolite, biofilm, adhesion and signal response related factors. Further phenotypic analysis of four of these regions shows that the encoded factors cause striking cellular phenotypes relevant to infection biology, including apoptosis, formation of actin ‘tails’ and multi-nucleation within treated macrophages. The detailed analysis of the remaining host of loci will facilitate genetic dissection of the interaction of this important pathogen with host macrophages and thus further elucidate this critical part of its infection cycle.
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影响因子：
3.6
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