| Autor: |
Martina Rossitto, Valeria Fox, Gianluca Vrenna, Vanessa Tuccio Guarna Assanti, Nour Essa, Maria Stefania Lepanto, Serena Raimondi, Marilena Agosta, Venere Cortazzo, Vanessa Fini, Annarita Granaglia, Enza Montemitro, Renato Cutrera, Carlo Federico Perno, Paola Bernaschi |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Microorganisms, Vol 12, Iss 10, p 2051 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2076-2607 |
| DOI: |
10.3390/microorganisms12102051 |
| Popis: |
Cystic fibrosis (CF) is a life-threatening genetic disease characterised by chronic lung infections sustained by opportunistic pathogens such as Pseudomonas aeruginosa. During the chronic long-lasting lung infections, P. aeruginosa adapts to the host environment. Hypermutability, mainly due to defects in the DNA repair system, resulting in an increased spontaneous mutation rate, represents a way to boost the rapid adaptation frequently encountered in CF P. aeruginosa isolates. We selected 609 isolates from 51 patients with CF chronically colonised by P. aeruginosa to study, by full-length genome sequencing, the longitudinal evolution of the bacterium. We recovered at least one hypermutable (mutator) isolate in 57% of patients. By combining genomic information and phenotypic analyses, we followed the evolutionary pathways of the P. aeruginosa mutator strains, identifying their contribution to multi-drug resistance and the emergence of new sub-lineages. By implementing patient clinical data, we observed that mutators preferentially follow a specific evolutionary trajectory in patients with a negative clinical outcome and that maintenance antibiotic polytherapy, based on alternating molecules, apparently reduces the occurrence of hypermutability. Finally, we draw attention to the possibility that modulator-induced changes in the pulmonary environment may be associated with the onset of hypermutability. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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