Ridderberg Winnie, Nielsen Signe Maria, Nørskov-Lauritsen Niels
Department of Clinical Microbiology, Aarhus University Hospital, Aarhus, Denmark.
Department of Clinical Microbiology, Aarhus University Hospital, Aarhus, Denmark; Institute of Clinical Medicine, Health, Aarhus University, Aarhus, Denmark.
PLoS One. 2015 Aug 27;10(8):e0136790. doi: 10.1371/journal.pone.0136790. eCollection 2015.
Achromobacter species are increasingly isolated from the respiratory tract of cystic fibrosis patients and often a chronic infection is established. How Achromobacter sp. adapts to the human host remains uncharacterised. By comparing longitudinally collected isolates of Achromobacter sp. isolated from five CF patients, we have investigated the within-host evolution of clonal lineages. The majority of identified mutations were isolate-specific suggesting co-evolution of several subpopulations from the original infecting isolate. The largest proportion of mutated genes were involved in the general metabolism of the bacterium, but genes involved in virulence and antimicrobial resistance were also affected. A number of virulence genes required for initiation of acute infection were selected against, e.g. genes of the type I and type III secretion systems and genes related to pilus and flagellum formation or function. Six antimicrobial resistance genes or their regulatory genes were mutated, including large deletions affecting the repressor genes of an RND-family efflux pump and a beta-lactamase. Convergent evolution was observed for five genes that were all implicated in bacterial virulence. Characterisation of genes involved in adaptation of Achromobacter to the human host is required for understanding the pathogen-host interaction and facilitate design of future therapeutic interventions.
无色杆菌属细菌越来越多地从囊性纤维化患者的呼吸道中分离出来，并且常常会形成慢性感染。无色杆菌属如何适应人类宿主仍不清楚。通过比较从五名囊性纤维化患者纵向收集的无色杆菌属分离株，我们研究了克隆谱系在宿主体内的进化。大多数已鉴定的突变是分离株特异性的，这表明从最初感染的分离株中几个亚群共同进化。突变基因中最大比例涉及细菌的一般代谢，但与毒力和抗菌抗性相关的基因也受到影响。一些引发急性感染所需的毒力基因被淘汰，例如I型和III型分泌系统的基因以及与菌毛和鞭毛形成或功能相关的基因。六个抗菌抗性基因或其调控基因发生了突变，包括影响RND家族外排泵阻遏基因和一个β-内酰胺酶的大片段缺失。观察到五个均与细菌毒力有关的基因发生了趋同进化。为了理解病原体与宿主的相互作用并促进未来治疗干预措施的设计，需要对参与无色杆菌适应人类宿主的基因进行表征。
