Data from: High virulence sub-populations in Pseudomonas aeruginosa long-term cystic fibrosis airway infections

Background: Pseudomonas aeruginosa typically displays loss of virulence-associated secretions over the course of chronic cystic fibrosis infections. This has led to the suggestion that virulence is a costly attribute in chronic infections. However, previous reports suggest that overproducing (OP) virulent pathotypes can coexist with non-producing mutants in the CF lung for many years. The consequences of such within-patient phenotypic diversity for the success of this pathogen are not fully understood. Here, we provide in-depth quantification of within-host variation in the production of three virulence associated secretions in the Liverpool cystic fibrosis epidemic strain of P. aeruginosa, and investgate the effect of this phenotypic variation on virulence in acute infections of an insect host model. Results: Within-patient variation was present for all three secretions (pyoverdine, pyocyanin and LasA protease). In two out of three patients sampled, OP isolates coexisted with under-producing mutants. In the third patient, all 39 isolates were under-producers of all three secretions relative to the transmissible ancestor LESB58. Finally, this phenotypic variation translated into variation in virulence in an insect host model. Conclusions: Within population variation in the production of P. aeruginosa virulence-associated secretions can lead to high virulence sub-populations persisting in patients with chronic CF infections.

研究背景：铜绿假单胞菌（Pseudomonas aeruginosa）在慢性囊性纤维化感染过程中，通常会出现毒力相关分泌产物的丢失。这一现象提示，在慢性感染中，毒力表达是一种具有适应性代价的性状。然而，既往研究表明，高分泌（OP）型毒力致病株可与非分泌突变株在囊性纤维化患者肺部共存多年。此类患者体内的表型多样性对该病原菌定植成功的影响尚未被完全阐明。本研究针对铜绿假单胞菌（Pseudomonas aeruginosa）利物浦囊性纤维化流行菌株，对其三种毒力相关分泌产物的宿主体内表达差异进行了深度定量分析，并探究了该表型差异对昆虫宿主急性感染模型中毒力的影响。

研究结果：三种分泌产物（绿脓杆菌素（pyoverdine）、绿脓菌素（pyocyanin）及LasA蛋白酶（LasA protease））均存在患者体内的表达差异。在3名受试患者中，有2名的样本里，高分泌（OP）型分离株与低分泌突变株共存。在第3名患者中，相较于可传播的祖先菌株LESB58，其全部39株分离株均为三种分泌产物的低分泌表型。最终，该表型差异可反映为昆虫宿主感染模型中的毒力差异。

研究结论：铜绿假单胞菌毒力相关分泌产物的群体内表达差异，可使高毒力亚群在慢性囊性纤维化感染患者体内持续存在。