Izydorczyk Conrad, Waddell Barbara J, Thornton Christina S, Conly John M, Rabin Harvey R, Somayaji Ranjani, Surette Michael G, Church Deirdre L, Parkins Michael D
Department of Microbiology, Immunology, and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Department of Medicine, Cumming School of Medicine, University of Calgary and Alberta Health Services, Calgary, AB, Canada.
Front Microbiol. 2023 Jun 15;14:1205389. doi: 10.3389/fmicb.2023.1205389. eCollection 2023.
is an opportunistic pathogen infecting persons with cystic fibrosis (pwCF) and portends a worse prognosis. Studies of infection dynamics have been limited by cohort size and follow-up. We investigated the natural history, transmission potential, and evolution of in a large Canadian cohort of 321 pwCF over a 37-year period.
One-hundred sixty-two isolates from 74 pwCF (23%) were typed by pulsed-field gel electrophoresis, and shared pulsotypes underwent whole-genome sequencing.
was recovered at least once in 82 pwCF (25.5%). Sixty-four pwCF were infected by unique pulsotypes, but shared pulsotypes were observed between 10 pwCF. In chronic carriage, longer time periods between positive sputum cultures increased the likelihood that subsequent isolates were unrelated. Isolates from individual pwCF were largely clonal, with differences in gene content being the primary source of genetic diversity objectified by gene content differences. Disproportionate progression of CF lung disease was not observed amongst those infected with multiple strains over time (versus a single) or amongst those with shared clones (versus strains only infecting one patient). We did not observe evidence of patient-to-patient transmission despite relatedness between isolates. Twenty-four genes with ≥ 2 mutations accumulated over time were identified across 42 sequenced isolates from all 11 pwCF with ≥ 2 sequenced isolates, suggesting a potential role for these genes in adaptation of to the CF lung.
Genomic analyses suggested common, indirect sources as the origins of infections in the clinic population. The information derived from a genomics-based understanding of the natural history of infection within CF provides unique insight into its potential for in-host evolution.
是一种机会性病原体，可感染囊性纤维化患者（pwCF），并预示着更差的预后。感染动态的研究受到队列规模和随访的限制。我们在一个由321名pwCF组成的加拿大大型队列中，对37年间的自然史、传播潜力和进化进行了调查。
对来自74名pwCF（23%）的162株分离株进行脉冲场凝胶电泳分型，对共享脉冲型进行全基因组测序。
在82名pwCF（25.5%）中至少回收了一次。64名pwCF被独特的脉冲型感染，但在10名pwCF之间观察到共享脉冲型。在慢性携带中，阳性痰培养之间较长的时间间隔增加了后续分离株不相关的可能性。来自个体pwCF的分离株在很大程度上是克隆性的，基因含量差异是通过基因含量差异客观化的遗传多样性的主要来源。随着时间的推移，在感染多种菌株的患者中（与单一菌株相比）或在共享克隆的患者中（与仅感染一名患者的菌株相比），未观察到CF肺部疾病的不成比例进展。尽管分离株之间存在相关性，但我们未观察到患者间传播的证据。在来自所有11名有≥2株测序分离株的pwCF的42株测序分离株中，鉴定出24个随着时间积累了≥2个突变的基因，表明这些基因在适应CF肺部方面可能发挥作用。
基因组分析表明，常见的间接来源是临床人群中感染的起源。基于基因组学对CF内感染自然史的理解所获得的信息，为其在宿主体内进化的潜力提供了独特的见解。
