Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients
Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients
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DOI：
10.1073/pnas.0602138103
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发表时间：
2006-05-30
影响因子：
11.1
通讯作者：
Olson, Maynard V.
中科院分区：
文献类型：
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作者：
Smith, Eric E.;Buckley, Danielle G.;Olson, Maynard V.
在许多人类感染中，宿主和病原体共存数年或数十年。重要的例子包括艾滋病毒、疱疹病毒、结核病、麻风病和疟疾。除了对艾滋病毒/艾滋病等病毒感染的深入研究外，人们对病原体长期感染期间发生的克隆性扩张在多大程度上涉及重要的遗传适应知之甚少。我们在这里报告了一个这样的感染的详细的全基因组分析，这是一例囊性纤维化(CF)患者，由条件致病菌铜绿假单胞菌引起。在感染的8年中，细菌经历了多次的遗传适应，整个基因组上的正选择信号和特定基因中的压倒性信号证明了这一点，其中几个基因在大多数CIF感染过程中发生了突变。特别令人感兴趣的是，我们发现，在慢性感染期间，启动急性感染所需的毒力因子经常被选择来对抗。显然，晚期CF感染的铜绿假单胞菌菌株的基因分型与“野生型”铜绿假单胞菌存在系统性差异，这些差异可能为这种慢性疾病的治疗提供新的机会。
In many human infections, hosts and pathogens coexist for years or decades. Important examples include HIV, herpes viruses, tuberculosis, leprosy, and malaria. With the exception of intensively studied viral infections such as HIV/AIDs, little is known about the extent to which the clonal expansion that occurs during long-term infection by pathogens involves important genetic adaptations. We report here a detailed, whole-genome analysis of one such infection, that of a cystic fibrosis (CF) patient by the opportunistic bacterial pathogen Pseudomonas aeruginosa. The bacteria underwent numerous genetic adaptations during 8 years of infection, as evidenced by a positive-selection signal across the genome and an overwhelming signal in specific genes, several of which are mutated during the course of most CIF infections. Of particular interest is our finding that virulence factors that are required for the initiation of acute infections are often selected against during chronic infections. It is apparent that the genotypes of the A aeruginosa strains present in advanced CF infections differ systematically from those of "wild-type" P. aeruginosa and that these differences may offer new opportunities for treatment of this chronic disease.