Department of Internal Medicine, Respiratory Medicine Section, Copenhagen University Hospital-Herlev and Gentofte Hospital, Herlev and Gentofte, Denmark.
Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Clin Microbiol Infect. 2022 Jul;28(7):990-995. doi: 10.1016/j.cmi.2022.01.017. Epub 2022 Feb 3.
It is unclear whether recurrent sputum culture with Pseudomonas aeruginosa from patients with chronic obstructive pulmonary disease (COPD) is caused by intermittent airway carriage by different P. aeruginosa lineages or persistent carriage by the same lineage, and whether lineages genetically adapt during carriage.
Whole-genome sequencing was performed for P. aeruginosa isolates sampled longitudinally from sputum cultures in patients with COPD who were enrolled in an ongoing randomized controlled trial (clinicaltrials.gov: NCT03262142).
A total of 153 P. aeruginosa isolates were sequenced for 23 patients during 365 days of follow-up. Recurrent presence of P. aeruginosa was seen in 19 patients (83%) and was caused by persistence of the same clonal lineage in all but one patient. We identified 38 genes mutated in parallel in two or more lineages, suggesting positive selection for adaptive mutations. Mutational enrichment analysis revealed genes important in antibiotic resistance and chronic infections to be more frequently mutated.
Recurrent P. aeruginosa was common and carried for a prolonged time after initial detection in the airways of patients with COPD. Recurrence was caused by persistence of the same clonal lineage and was associated with genetic adaptation. Trial data on possible clinical benefits of attempting antibiotic eradication of P. aeruginosa in COPD are warranted.
目前尚不清楚慢性阻塞性肺疾病（COPD）患者反复出现铜绿假单胞菌肺部感染是由不同铜绿假单胞菌谱系间歇性气道携带引起，还是由同一谱系持续携带引起，以及在携带过程中谱系是否发生遗传适应性改变。
对正在进行的一项随机对照试验（clinicaltrials.gov：NCT03262142）中 COPD 患者纵向痰液培养中分离的铜绿假单胞菌分离株进行全基因组测序。
在 365 天的随访中，对 23 名患者的 153 株铜绿假单胞菌分离株进行了测序。19 名患者（83%）出现反复铜绿假单胞菌感染，除一名患者外，所有患者均由同一克隆谱系持续存在引起。我们发现 38 个基因在两个或更多谱系中平行发生突变，表明适应性突变受到正向选择。突变丰度分析显示，与抗生素耐药和慢性感染相关的基因更频繁发生突变。
在 COPD 患者的气道中初次检测到铜绿假单胞菌后，其反复出现且持续存在很长时间。复发是由同一克隆谱系的持续存在引起的，并与遗传适应性有关。需要进行临床试验以评估尝试清除 COPD 患者铜绿假单胞菌的抗生素治疗的潜在临床获益。
