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Open AccessArticle

Hypermutation as an Evolutionary Mechanism for Achromobacter xylosoxidans in Cystic Fibrosis Lung Infection

1
Laboratory of Computational Genomics, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy
2
Department of Diagnostics and Public Health, Microbiology Section, University of Verona, 37134 Verona, Italy
3
Department of Clinical Microbiology, Rigshospitalet, 2100 Copenhagen, Denmark
4
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
*
Author to whom correspondence should be addressed.
Equal contributions.
Equal contributions.
Pathogens 2020, 9(2), 72; https://doi.org/10.3390/pathogens9020072
Received: 16 December 2019 / Revised: 15 January 2020 / Accepted: 16 January 2020 / Published: 21 January 2020
(This article belongs to the Section Human Pathogens)
Achromobacter xylosoxidans can cause chronic infections in the lungs of patients with cystic fibrosis (CF) by adapting to the specific environment. The study of longitudinal isolates allows to investigate its within-host evolution to unravel the adaptive mechanisms contributing to successful colonization. In this study, four clinical isolates longitudinally collected from two chronically infected patients underwent whole genome sequencing, de novo assembly and sequence analysis. Phenotypic assays were also performed. The isolates coming from one of the patients (patient A) presented a greater number of genetic variants, diverse integrative and conjugative elements, and different protease secretion. In the first of these isolates (strain A1), we also found a large deletion in the mutS gene, involved in DNA mismatch repair (MMR). In contrast, isolates from patient B showed a lower number of variants, only one integrative and mobilizable element, no phenotypic changes, and no mutations in the MMR system. These results suggest that in the two patients the establishment of a chronic infection was mediated by different adaptive mechanisms. While the strains isolated from patient B showed a longitudinal microevolution, strain A1 can be clearly classified as a hypermutator, confirming the occurrence and importance of this adaptive mechanism in A. xylosoxidans infection. View Full-Text
Keywords: lung infection; opportunistic pathogen; bacterial evolution; comparative genomics; clonal diversification lung infection; opportunistic pathogen; bacterial evolution; comparative genomics; clonal diversification
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Veschetti, L.; Sandri, A.; Krogh Johansen, H.; Lleò, M.M.; Malerba, G. Hypermutation as an Evolutionary Mechanism for Achromobacter xylosoxidans in Cystic Fibrosis Lung Infection. Pathogens 2020, 9, 72.

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