Abstract
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.
Highlights
Achromobacter spp. are emerging pathogens causing chronic bacterial infections in patients with cystic fibrosis (CF) [1,2,3,4]; it is still unclear to what extent Achromobacter spp. infections impact morbidity and mortality in these patients [3,4,5]
All isolates were previously defined as belonging to five different species: A. ruhlandii (N=29), A. insuavis (N=18), A. xylosoxidans (N=52), A. aegrifaciens (N=1) and a new genogroup (N=1)
The remaining 99 Achromobacter spp. genomes were grouped to 61 lineages, which were defined as all isolates from one patient belonging to the same species and clone type (Table S1, available in the online version of this article)
Summary
Achromobacter spp. are emerging pathogens causing chronic bacterial infections in patients with CF [1,2,3,4]; it is still unclear to what extent Achromobacter spp. infections impact morbidity and mortality in these patients [3,4,5]. While conventional CF pathogens, e.g. Pseudomonas aeruginosa and Staphylococcus aureus, are studied extensively, little is known about the extent withinand between-patient genetic adaptation has in Achromobacter spp. infections, A. ruhlandii, A. insuavis and. A. xylosoxidans as they were shown by Gade et al to be the main cause of chronic, long-term infections in patients with CF infected with Achromobacter spp. We analysed 101 previously whole-genome-s equenced (WGS) Achromobacter spp. isolates from 51 patients to investigate the genetic relatedness and within-host genetic changes of Achromobacter spp. over the course of up to 20 years of infections. We aimed to identify the main gene content differences between and within Achromobacter spp. isolates
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