Transmission and genetic adaptation of Achromobacter in cystic fibrosis

Published: Aug. 4, 2020, 5:02 a.m.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.04.235952v1?rss=1 Authors: Gabrielaite, M., Norskov-Lauritsen, N., Nielsen, F. C., Johansen, H. K., Marvig, R. L. Abstract: Achromobacter species are increasingly being detected in patients with cystic fibrosis (CF), and this emerging pathogen has been associated with antibiotic resistance and more severe disease outcomes. Nonetheless, little is known about the extent of transmission and genetic adaptation in Achromobacter infections. We sequenced the genomes of 101 clinical isolates of Achromobacter collected from 51 patients with CF-the largest longitudinal dataset to-date. We performed a comprehensive pathogenomic analysis to identify pathogen population structure, within-host adaptation, mutational signatures, patient-to-patient transmission events, and associated genetic variation with antibiotic resistance phenotypes. We found that the population of Achromobacter isolates was composed of five different species where A. xylosoxidans accounted for 52% of the infections. Most patients were infected by unique Achromobacter clone types; nonetheless, patient-to-patient transmission events identified by shared clone types were observed in 35% (N=18) of patients. We found that the same regulatory and inorganic ion transport genes were frequently mutated in persisting clone types within and between species indicating convergent genetic adaptation. Genome-wide association study (GWAS) of six antibiotic resistance phenotypes revealed that the majority of associated genes were involved in transcription and inorganic ion transport. Overall, we provide insight into pathogenomics of chronic Achromobacter infections and show the relevance of whole genome sequencing of clinical isolates. Our findings on evolution and genetic adaptation can facilitate the understanding of disease progression, inform antibiotic treatment, and identify patient-to-patient transmission. Copy rights belong to original authors. Visit the link for more info