Markussen Trine, Marvig Rasmus Lykke, Gómez-Lozano María, Aanæs Kasper, Burleigh Alexandra E, Høiby Niels, Johansen Helle Krogh, Molin Søren, Jelsbak Lars
Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
Department of Otorhinolaryngology, Head and Neck Surgery, Rigshospitalet and Faculty of Health Sciences, Copenhagen, Denmark.
mBio. 2014 Sep 16;5(5):e01592-14. doi: 10.1128/mBio.01592-14.
Microbial population polymorphisms are commonly observed in natural environments, including long-term infected hosts. However, the underlying processes promoting and stabilizing diversity are difficult to unravel and are not well understood. Here, we use chronic infection of cystic fibrosis airways by the opportunistic pathogen Pseudomonas aeruginosa as a system for investigating bacterial diversification processes during the course of infection. We analyze clonal bacterial isolates sampled during a 32-year period and map temporal and spatial variations in population diversity to different infection sites within the infected host. We show that the ancestral infecting strain diverged into distinct sublineages, each with their own functional and genomic signatures and rates of adaptation, immediately after initial colonization. The sublineages coexisted in the host for decades, suggesting rapid evolution of stable population polymorphisms. Critically, the observed generation and maintenance of population diversity was the result of partitioning of the sublineages into physically separated niches in the CF airway. The results reveal a complex within-host population structure not previously realized and provide evidence that the heterogeneity of the highly structured and complex host environment promotes the evolution and long-term stability of pathogen population diversity during infection.
Within-host pathogen evolution and diversification during the course of chronic infections is of importance in relation to therapeutic intervention strategies, yet our understanding of these processes is limited. Here, we investigate intraclonal population diversity in P. aeruginosa during chronic airway infections in cystic fibrosis patients. We show the evolution of a diverse population structure immediately after initial colonization, with divergence into multiple distinct sublineages that coexisted for decades and occupied distinct niches. Our results suggest that the spatial heterogeneity in CF airways plays a major role in relation to the generation and maintenance of population diversity and emphasize that a single isolate in sputum may not represent the entire pathogen population in the infected individual. A more complete understanding of the evolution of distinct clonal variants and their distribution in different niches could have positive implications for efficient therapy.
微生物种群多态性在自然环境中普遍存在，包括长期感染的宿主。然而，促进和稳定多样性的潜在过程难以阐明，人们对此也了解不足。在此，我们将机会性病原体铜绿假单胞菌对囊性纤维化气道的慢性感染作为一个系统，用于研究感染过程中的细菌多样化过程。我们分析了在32年期间采集的克隆细菌分离株，并将种群多样性的时间和空间变化映射到受感染宿主内的不同感染部位。我们发现，初始定植后，祖先感染菌株立即分化为不同的亚谱系，每个亚谱系都有其自身的功能、基因组特征和适应率。这些亚谱系在宿主体内共存了数十年，表明稳定的种群多态性在快速进化。至关重要的是，观察到的种群多样性的产生和维持是亚谱系在囊性纤维化气道中被分隔到物理上分离的生态位的结果。这些结果揭示了一种以前未认识到的复杂的宿主体内种群结构，并提供证据表明，高度结构化和复杂的宿主环境的异质性促进了感染期间病原体种群多样性的进化和长期稳定性。
慢性感染过程中宿主体内病原体的进化和多样化对于治疗干预策略至关重要，但我们对这些过程的理解有限。在此，我们研究了囊性纤维化患者慢性气道感染期间铜绿假单胞菌的克隆内种群多样性。我们发现，初始定植后立即出现了多样化的种群结构进化，分化为多个不同的亚谱系，这些亚谱系共存了数十年并占据不同的生态位。我们的结果表明，囊性纤维化气道中的空间异质性在种群多样性的产生和维持方面发挥了主要作用，并强调痰液中的单个分离株可能不代表受感染个体中的整个病原体种群。更全面地了解不同克隆变体的进化及其在不同生态位中的分布可能对有效治疗有积极影响。
