Jelsbak Lars, Johansen Helle Krogh, Frost Anne-Louise, Thøgersen Regitze, Thomsen Line E, Ciofu Oana, Yang Lei, Haagensen Janus A J, Høiby Niels, Molin Søren
Infection Microbiology Group, BioCentrum-DTU, Technical University of Denmark, Building 301, 2800 Lyngby, Denmark.
Infect Immun. 2007 May;75(5):2214-24. doi: 10.1128/IAI.01282-06. Epub 2007 Jan 29.
The ability to establish lifelong persistent infections is a fundamental aspect of the interactions between many pathogenic microorganisms and their mammalian hosts. One example is chronic lung infections by the opportunistic pathogen Pseudomonas aeruginosa in cystic fibrosis (CF) patients. This infection process is associated with extensive genetic adaptation and microevolution of the infecting bacteria. Through investigations of P. aeruginosa populations and infection dynamics in a group of CF patients followed at the Danish CF Clinic in Copenhagen, we have identified two distinct and dominant clones that have evolved into highly successful colonizers of CF patient airways. A significant component of the evolutionary success of these two clones has been their efficient transmissibility among the CF patients. The two clones have been present and transmitted among different CF patients for more than 2 decades. Our data also suggest that the P. aeruginosa population structure in the CF patient airways has been influenced by competition between different clones and that the two dominant clones have been particularly competitive within the lungs, which may add to their overall establishment success. In contrast, we show that adaptive traits commonly associated with establishment of chronic P. aeruginosa infections of CF patients, such as transition to the mucoid phenotype and production of virulence factors, play minor roles in the ability of the two dominant clones to spread among patients and cause long-term chronic infections. These findings suggest that hitherto-unrecognized evolutionary pathways may be involved in the development of successful and persistent P. aeruginosa colonizers of CF patient lungs.
建立终身持续性感染的能力是许多致病微生物与其哺乳动物宿主之间相互作用的一个基本方面。一个例子是囊性纤维化(CF)患者肺部被机会性病原体铜绿假单胞菌慢性感染。这种感染过程与感染细菌的广泛基因适应和微进化有关。通过对哥本哈根丹麦CF诊所随访的一组CF患者中铜绿假单胞菌群体和感染动态的调查,我们确定了两个不同的优势克隆,它们已进化成为CF患者气道中非常成功的定植菌。这两个克隆进化成功的一个重要因素是它们在CF患者之间的高效传播性。这两个克隆在不同的CF患者中存在并传播了20多年。我们的数据还表明,CF患者气道中的铜绿假单胞菌群体结构受到不同克隆之间竞争的影响,并且这两个优势克隆在肺部特别具有竞争力,这可能增加了它们整体定植成功的几率。相比之下,我们表明,通常与CF患者慢性铜绿假单胞菌感染建立相关的适应性特征,如转变为黏液样表型和产生毒力因子,在这两个优势克隆在患者之间传播并引起长期慢性感染的能力中起次要作用。这些发现表明,迄今未被认识的进化途径可能参与了CF患者肺部成功且持续的铜绿假单胞菌定植菌的发展。