Achromobacter spp. are emerging pathogens in patients with cystic fibrosis (CF) and Achromobacter spp. caused infections are associated with more severe disease outcomes and high intrinsic antibiotic resistance. While conventional CF pathogens are studied extensively, little is known about the genetic determinants leading to antibiotic resistance and the genetic adaptation in Achromobacter spp. infections. Here, we analysed 101 Achromobacter spp. genomes from 51 patients with CF isolated during the course of up to 20 years of infection to identify within-host adaptation, mutational signatures and genetic variation associated with increased antibiotic resistance. We found that the same regulatory and inorganic ion transport genes were frequently mutated in persisting clone types within and between Achromobacter species, indicating convergent genetic adaptation. Genome-wide association study of six antibiotic resistance phenotypes revealed the enrichment of associated genes involved in inorganic ion transport, transcription gene enrichment in β-lactams, and energy production and translation gene enrichment in the trimethoprim/sulfonamide group. Overall, we provide insights into the pathogenomics of Achromobacter spp. infections in patients with CF airways. Since emerging pathogens are increasingly recognized as an important healthcare issue, our findings on evolution of antibiotic resistance and genetic adaptation can facilitate better understanding of disease progression and how mutational changes have implications for patients with CF.

中文翻译：

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无色杆菌属 囊性纤维化的遗传适应

无色杆菌 属 是囊性纤维化 (CF) 和无色杆菌属患者中出现的病原体。引起的感染与更严重的疾病结果和高内在抗生素耐药性相关。虽然传统的 CF 病原体得到了广泛的研究，但对导致抗生素耐药性的遗传决定因素和无色杆菌属的遗传适应却知之甚少。感染。在这里，我们分析了 101 个无色杆菌属。研究人员从 51 名 CF 患者的基因组中分离出长达 20 年的感染过程，以确定宿主内适应、突变特征和与抗生素耐药性增加相关的遗传变异。我们发现，在无色杆菌属物种内部和之间的持久克隆类型中，相同的调节和无机离子转运基因经常发生突变，这表明趋同的遗传适应。六种抗生素耐药表型的全基因组关联研究揭示了涉及无机离子转运的相关基因的富集、β-内酰胺中转录基因的富集以及甲氧苄啶/磺酰胺组中能量产生和翻译基因的富集。总体而言，我们提供了对无色杆菌属的病原体组学的见解。CF 气道患者的感染。由于新兴病原体越来越被认为是一个重要的医疗保健问题，我们关于抗生素耐药性和遗传适应进化的发现可以促进更好地了解疾病进展以及突变变化如何对 CF 患者产生影响。