Objectives: Hypermutable strains of Pseudomonas aeruginosa frequently emerge during chronic airways infection in cystic fibrosis (CF) patients. While the increased accumulation of mutations by hypermutable strains determines a biological cost for the colonization of secondary environments, the mutator phenotypes might confer a selective advantage under antibiotic treatment in a CF airways environment. Methods: To test this hypothesis, the reference strain PAO1 and clonal pairs of CF clinical hypermutable and wild-type P. aeruginosa strains belonging to different genotypes were subjected to competition experiments in vitro and in a mouse model of chronic infection. Results: Both in vitro and in vivo, under antibiotic selection pressure, clinical hypermutable P. aeruginosa strains and the reference PAO1ΔmutS outcompeted their wild-type strains, promoting P. aeruginosa hypermutable strains in the airways colonization. This advantage for the hypermutable strain did not occur in the absence of antibiotic treatments. Severe histopathological lesions were detected during chronic murine airways infection after antibiotic pressure, indicating that the advantage of the hypermutable population in the lungs may contribute to disease progression. Conclusions: Overall, these results showed that P. aeruginosa hypermutability, previously associated with a biological cost, increases colonization potential under selection pressure in a context of CF chronic airways infection and can contribute to lung damage during long-term persistence.

Antibiotic pressure compensates the biological cost associated with Pseudomonas aeruginosa hypermutable phenotypes in vitro and in a murine model of chronic airways infection / B. Alcala-Franco, S. Montanari, C. Cigana, G. Bertoni, A. Oliver, A. Bragonzi. - In: JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. - ISSN 0305-7453. - 67:4(2012), pp. dkr587.962-dkr587.969.

Antibiotic pressure compensates the biological cost associated with Pseudomonas aeruginosa hypermutable phenotypes in vitro and in a murine model of chronic airways infection

G. Bertoni;
2012

Abstract

Objectives: Hypermutable strains of Pseudomonas aeruginosa frequently emerge during chronic airways infection in cystic fibrosis (CF) patients. While the increased accumulation of mutations by hypermutable strains determines a biological cost for the colonization of secondary environments, the mutator phenotypes might confer a selective advantage under antibiotic treatment in a CF airways environment. Methods: To test this hypothesis, the reference strain PAO1 and clonal pairs of CF clinical hypermutable and wild-type P. aeruginosa strains belonging to different genotypes were subjected to competition experiments in vitro and in a mouse model of chronic infection. Results: Both in vitro and in vivo, under antibiotic selection pressure, clinical hypermutable P. aeruginosa strains and the reference PAO1ΔmutS outcompeted their wild-type strains, promoting P. aeruginosa hypermutable strains in the airways colonization. This advantage for the hypermutable strain did not occur in the absence of antibiotic treatments. Severe histopathological lesions were detected during chronic murine airways infection after antibiotic pressure, indicating that the advantage of the hypermutable population in the lungs may contribute to disease progression. Conclusions: Overall, these results showed that P. aeruginosa hypermutability, previously associated with a biological cost, increases colonization potential under selection pressure in a context of CF chronic airways infection and can contribute to lung damage during long-term persistence.
Chronic airway infection; Cystic fibrosis; Hypermutators; Mouse model; P. aeruginosa
Settore BIO/19 - Microbiologia Generale
2012
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/212061
Citazioni
  • ???jsp.display-item.citation.pmc??? 6
  • Scopus 13
  • ???jsp.display-item.citation.isi??? 13
social impact