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囊性纤维化气道克隆性系列分离株在人中性粒细胞中的竞争性存活

Competitive survival of clonal serial isolates from cystic fibrosis airways in human neutrophils.

作者信息

Kuschnerow Pia, Munder Antje, de Buhr Nicole, Mörgelin Matthias, Jirmo Adan Chari, Ackermann Mania, von Köckritz-Blickwede Maren, Tümmler Burkhard, Cramer Nina

机构信息

Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.

German Center for Infection Research (DZIF), 30625 Hannover, Germany.

出版信息

iScience. 2023 Mar 24;26(4):106475. doi: 10.1016/j.isci.2023.106475. eCollection 2023 Apr 21.

Abstract

Chronic airway infections with are the major co-morbidity in most people with cystic fibrosis (CF) sustained by neutrophils as the major drivers of lung inflammation, damage, and remodeling. Phagocytosis assays were performed with clonal consortia of longitudinal airway isolates collected from people with CF since the onset of lung colonization until patient's death or replacement by another clone. The extra- and intracellular abundance of individual strains was assessed by deep amplicon sequencing of strain-specific single nucleotide variants in the bacterial genome. The varied microevolution of the accessory genome of the clones during mild and severe courses of infection corresponded with a differential persistence of clonal progeny in the neutrophil phagosome. By simultaneously exposing the ancestor and its progeny to the same habitat, the study recapitulated the time lapse of the temporal change of the fitness of the clone to survive in neutrophils.

摘要

慢性气道感染是大多数囊性纤维化(CF)患者的主要合并症,中性粒细胞是肺部炎症、损伤和重塑的主要驱动因素。吞噬试验是用从CF患者肺部定植开始直至患者死亡或被另一个克隆取代期间收集的纵向气道分离株的克隆联合体进行的。通过对细菌基因组中菌株特异性单核苷酸变异进行深度扩增子测序,评估各个菌株在细胞外和细胞内的丰度。在轻度和重度感染过程中,这些克隆的辅助基因组的不同微进化与克隆后代在中性粒细胞吞噬体中的不同持久性相对应。通过同时将祖先及其后代暴露于相同的环境中,该研究重现了克隆在中性粒细胞中生存适应性随时间变化的时间间隔。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec34/10122015/7ab47c468a90/fx1.jpg

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