Hypermutation as an Evolutionary Mechanism for <i>Achromobacter xylosoxidans</i> in Cystic Fibrosis Lung Infection
<i>Achromobacter xylosoxidans</i> 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...
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MDPI AG
2020-01-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/9/2/72 |
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| author | Laura Veschetti Angela Sandri Helle Krogh Johansen Maria M. Lleò Giovanni Malerba |
| author_facet | Laura Veschetti Angela Sandri Helle Krogh Johansen Maria M. Lleò Giovanni Malerba |
| author_sort | Laura Veschetti |
| collection | DOAJ |
| description | <i>Achromobacter xylosoxidans</i> 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 <i>mutS</i> 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 <i>A. xylosoxidans</i> infection. |
| first_indexed | 2024-04-12T19:57:33Z |
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| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-04-12T19:57:33Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
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| spelling | doaj.art-50d1014212af411693e30f897f3096a62022-12-22T03:18:37ZengMDPI AGPathogens2076-08172020-01-01927210.3390/pathogens9020072pathogens9020072Hypermutation as an Evolutionary Mechanism for <i>Achromobacter xylosoxidans</i> in Cystic Fibrosis Lung InfectionLaura Veschetti0Angela Sandri1Helle Krogh Johansen2Maria M. Lleò3Giovanni Malerba4Laboratory of Computational Genomics, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, ItalyDepartment of Diagnostics and Public Health, Microbiology Section, University of Verona, 37134 Verona, ItalyDepartment of Clinical Microbiology, Rigshospitalet, 2100 Copenhagen, DenmarkDepartment of Diagnostics and Public Health, Microbiology Section, University of Verona, 37134 Verona, ItalyLaboratory of Computational Genomics, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy<i>Achromobacter xylosoxidans</i> 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 <i>mutS</i> 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 <i>A. xylosoxidans</i> infection.https://www.mdpi.com/2076-0817/9/2/72lung infectionopportunistic pathogenbacterial evolutioncomparative genomicsclonal diversification |
| spellingShingle | Laura Veschetti Angela Sandri Helle Krogh Johansen Maria M. Lleò Giovanni Malerba Hypermutation as an Evolutionary Mechanism for <i>Achromobacter xylosoxidans</i> in Cystic Fibrosis Lung Infection Pathogens lung infection opportunistic pathogen bacterial evolution comparative genomics clonal diversification |
| title | Hypermutation as an Evolutionary Mechanism for <i>Achromobacter xylosoxidans</i> in Cystic Fibrosis Lung Infection |
| title_full | Hypermutation as an Evolutionary Mechanism for <i>Achromobacter xylosoxidans</i> in Cystic Fibrosis Lung Infection |
| title_fullStr | Hypermutation as an Evolutionary Mechanism for <i>Achromobacter xylosoxidans</i> in Cystic Fibrosis Lung Infection |
| title_full_unstemmed | Hypermutation as an Evolutionary Mechanism for <i>Achromobacter xylosoxidans</i> in Cystic Fibrosis Lung Infection |
| title_short | Hypermutation as an Evolutionary Mechanism for <i>Achromobacter xylosoxidans</i> in Cystic Fibrosis Lung Infection |
| title_sort | hypermutation as an evolutionary mechanism for i achromobacter xylosoxidans i in cystic fibrosis lung infection |
| topic | lung infection opportunistic pathogen bacterial evolution comparative genomics clonal diversification |
| url | https://www.mdpi.com/2076-0817/9/2/72 |
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