The respiratory tract of CF patients provides a selective environment favoring development and persistence of multiple P. aeruginosa pathogenic variants not eradicable by any known therapy. Whether P. aeruginosa clonal variants, including hypermutable strains, differ in their pathogenic potential is not known. Multiple genotypic analysis were performed in strains isolated from CF patients carrying the same clonal lineage from the onset of colonization over many years. PFGE, ATchip and multilocus SNPs showed intraclonal diversity with genome rearrangements, variations in pathogenic islands and acquisition of mutations in the muc genes and mutS, muL and uvrD genes of the mismatch repair system (MMR). To understand the role of hypermutation in the pathogenesis of chronic lung infection and antibiotic resistance, couples of clinical wild type/hypermutable clonally related P. aeruginosa strains and the isogenic laboratory strains PAO1/PAO1∆mutS were subjected to competition in murine model. After 14 days, P. aeruginosa hypermutable strains were less efficient than wild type in establishing chronic lung infection in C57Bl/6 mice. Under antibiotic treatment the results were opposed. In vitro, the hypermutable strains showed a higher level of resistance to 10 antibiotics and the MIC returned back to the level of the wild type strains when complemented with MMR genes. Our finding suggests that hypermutation is a key factor in development of multiple-antimicrobial resistance and may favor chronic colonization in CF patients under antibiotics treatment. Supported by the Italian CF Research Foundation.
|Titolo:||Lung pathogenesis of Pseudomonas aeruginosa hypermutable strains from patients with cystic fibrosis|
MONTANARI, SARA (Primo)
PARONI, MOIRA (Secondo)
|Data di pubblicazione:||ago-2008|
|Settore Scientifico Disciplinare:||Settore BIO/19 - Microbiologia Generale|
|Citazione:||Lung pathogenesis of Pseudomonas aeruginosa hypermutable strains from patients with cystic fibrosis / S. Montanari, M. Paroni, A. Oliver, B. Tummler, A. Bragonzi. ((Intervento presentato al 2. convegno European Cystic Fibrosis Young Investigator Meeting tenutosi a Lille, France nel 2008.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|