Background Pseudomonas aeruginosa is a multidrug-resistant pathogen causing recalcitrant pulmonary infections in people with cystic fibrosis (pwCF). Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have been developed that partially correct the defective chloride channel driving disease. Despite the many clinical benefits, studies in adults have demonstrated that while P. aeruginosa sputum load decreases, chronic infection persists. Here, we investigate how P. aeruginosa in pwCF may change in the altered lung environment after CFTR modulation. Methods P. aeruginosa strains (n = 105) were isolated from the sputum of 11 chronically colonized pwCF at baseline and up to 21 months posttreatment with elexacaftor-tezacaftor-ivacaftor or tezacaftor-ivacaftor. Phenotypic characterization and comparative genomics were performed. Results Clonal lineages of P. aeruginosa persisted after therapy, with no evidence of displacement by alternative strains. We identified commonly mutated genes among patient isolates that may be positively selected for in the CFTR-modulated lung. However, classic chronic P. aeruginosa phenotypes such as mucoid morphology were sustained, and isolates remained just as resistant to clinically relevant antibiotics. Conclusions Despite the clinical benefits of CFTR modulators, clonal lineages of P. aeruginosa persist that may prove just as difficult to manage in the future, especially in pwCF with advanced lung disease.

中文翻译：

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CFTR 调节对囊性纤维化患者铜绿假单胞菌感染的影响

背景 铜绿假单胞菌是一种多重耐药病原体，可导致囊性纤维化 (pwCF) 患者出现顽固性肺部感染。囊性纤维化跨膜电导调节剂（CFTR）调节剂已被开发出来，可以部分纠正有缺陷的氯通道驱动疾病。尽管有许多临床益处，但对成人的研究表明，虽然铜绿假单胞菌痰量减少，但慢性感染仍然存在。在这里，我们研究了 pwCF 中的铜绿假单胞菌在 CFTR 调节后如何改变肺部环境。方法 从 11 例长期定植的 pwCF 患者的痰液中分离出铜绿假单胞菌菌株（n = 105），该患者在基线时和使用 elexacaftor-tezacaftor-ivacaftor 或 tezacaftor-ivacaftor 治疗后长达 21 个月内。进行了表型表征和比较基因组学。结果 治疗后铜绿假单胞菌的克隆谱系仍然存在，没有证据表明被替代菌株取代。我们鉴定了患者分离株中常见的突变基因，这些基因可能在 CFTR 调节的肺中被积极选择。然而，经典的慢性铜绿假单胞菌表型（例如粘液形态）得以维持，并且分离株仍然对临床相关抗生素具有耐药性。结论 尽管 CFTR 调节剂具有临床益处，但铜绿假单胞菌的克隆谱系仍然存在，未来可能同样难以管理，尤其是患有晚期肺部疾病的 pwCF。