1887

Abstract

is the dominant pathogen causing chronic lung infections in patients with cystic fibrosis (CF). After an initial phase characterized by intermittent colonizations, a chronic infection is established upon conversion of from the non-mucoid to the mucoid, alginate-overproducing phenotype. During the chronic infection the isolation of both mucoid and non-mucoid isolates in CF sputum samples is very common. The purpose of the present study was to establish, by sequence analysis, the types of mutations present in the operon in a large number of mucoid and non-mucoid isolates from Scandinavian CF patients and in -derived non-mucoid revertants. Mucoid (83) and non-mucoid isolates (103) from 91 Scandinavian patients with chronic infection and 24 non-mucoid isolates from intermittently colonized CF patients were investigated. In addition, 88 spontaneous non-mucoid revertants obtained from nine mucoid CF isolates were also included in the study. Mutations in were found in 92 % of the mucoid and in up to 70 % of the non-mucoid isolates from chronically infected patients, indicating that the majority of non-mucoid isolates are revertants. None of the non-mucoid isolates from intermittently colonized CF patients harboured mutations. Although has been considered an important gene for secondary-site mutations responsible for reversion to non-mucoidy, only 30 % of the -mutated non-mucoid CF isolates had mutations in . In contrast, 83 % of the -derived spontaneous non-mucoid revertants had mutations in , showing that in the CF lung there is a selection for non-mucoid revertants with secondary-site mutations in genes other than . In addition, we report, to our knowledge for the first time, loss-of-function mutations in the negative regulators and in CF clinical isolates. In some of the CF isolates these mutations are associated with moderate alginate production. In conclusion, most non-mucoid isolates from chronically infected CF patients are revertants and the mechanism of revertance is -independent in the CF lung.

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2008-01-01
2020-02-19
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