Scientific Reports ( IF 3.8 ) Pub Date : 2022-09-21 , DOI: 10.1038/s41598-022-19240-2 Conrad Izydorczyk 1 , Barbara J Waddell 1 , Robert B Weyant 1, 2 , Michael G Surette 1, 3 , Ranjani Somayaji 1, 4, 5 , Harvey R Rabin 1, 4 , John M Conly 1, 4, 5, 6 , Deirdre L Church 1, 4, 5, 6 , Michael D Parkins 1, 4, 5
Haemophilus influenzae is a Gram-negative pathobiont, frequently recovered from the airways of persons with cystic fibrosis (pwCF). Previous studies of H. influenzae infection dynamics and transmission in CF predominantly used molecular methods, lacking resolution. In this retrospective cohort study, representative yearly H. influenzae isolates from all pwCF attending the Calgary Adult CF Clinic with H. influenzae positive sputum cultures between 2002 and 2016 were typed by pulsed-field gel electrophoresis. Isolates with shared pulsotypes common to ≥ 2 pwCF were sequenced by Illumina MiSeq. Phylogenetic and pangenomic analyses were used to assess genetic relatedness within shared pulsotypes, and epidemiological investigations were performed to assess potential for healthcare associated transmission. H. influenzae infection was observed to be common (33% of patients followed) and dynamic in pwCF. Most infected pwCF exhibited serial infections with new pulsotypes (75% of pwCF with ≥ 2 positive cultures), with up to four distinct pulsotypes identified from individual patients. Prolonged infection by a single pulsotype was only rarely observed. Intra-patient genetic diversity was observed at the single-nucleotide polymorphism and gene content levels. Seven shared pulsotypes encompassing 39% of pwCF with H. influenzae infection were identified, but there was no evidence, within our sampling scheme, of direct patient-to-patient infection transmission.
中文翻译:
感染囊性纤维化成人气道的流感嗜血杆菌的自然史和遗传多样性
流感嗜血杆菌是一种革兰氏阴性致病菌,经常从囊性纤维化 (pwCF) 患者的气道中回收。以前对 CF 中流感嗜血杆菌感染动力学和传播的研究主要使用分子方法,缺乏分辨率。在这项回顾性队列研究中,具有代表性的年度流感嗜血杆菌从所有参加卡尔加里成人 CF 诊所的流感嗜血杆菌分离株中分离出来通过脉冲场凝胶电泳对 2002 年至 2016 年间的阳性痰培养物进行分型。Illumina MiSeq 对具有 ≥ 2 pwCF 共有的共享脉冲型的分离株进行测序。系统发育和泛基因组分析用于评估共享脉搏型内的遗传相关性,并进行流行病学调查以评估与医疗保健相关的传播潜力。流感嗜血杆菌观察到感染在 pwCF 中很常见(33% 的患者被随访)和动态。大多数受感染的 pwCF 表现出新脉搏型的连续感染(75% 的 pwCF 有 ≥ 2 个阳性培养物),从个体患者中识别出多达四种不同的脉搏型。很少观察到单一脉搏型的长期感染。在单核苷酸多态性和基因含量水平上观察到患者内的遗传多样性。确定了七种共有的脉搏型,其中 39% 的 pwCF感染了流感嗜血杆菌,但在我们的抽样方案中,没有证据表明患者与患者之间存在直接感染传播。