P. AERUGINOSA NEW GE · Identification of new pseudomonas aeruginosa genes involved in the pathophysiology of cystic fibrosis lung infection
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2004-07-01 → 2005-06-30
- EU contribution
- €40,000
- Participants
- 1
- Scheme
- ERG
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Results in brief
Final Activity Report Summary - P. AERUGINOSA NEW GE (Identification of new Pseudomonas aeruginosa genes involved in the pathophysiology of Cystic Fibrosis lung infection)
Pseudomonas aeruginosa lung infection is the major cause of morbidity and mortality in Cystic fibrosis (CF) patients. During chronic colonisation the persisting pathogen adapts to the CF niche due to the disease-specific environmental conditions of the host, such as anaerobic mucus layer and the pressure of innate immune defence system. Under those conditions P. aeruginosa evolves specific virulence mechanisms to evade the host defence and increases its fitness / survival. Over-expression of alginate by P. aeruginosa leading to the mucoid phenotype and linked to mucABCD mutations is thought to be a key factor in the organisms' persistence in the CF respiratory tract. In the year covered by the ERG, a collection of clinical strains were screened for presence of muc mutations and correlated with CF pathogenesis. A lack of an association between muc genotype and severity of CF lung disease were found. Muc mutations were observed with similar frequency in strains collected from two groups of CF patients each with a highly discordant course of chronic P. aeruginosa infection, suggesting that carriage of strains with muc mutations is not informative for the clinical manifestations and prognosis of CF disease. However, when the collection of P. aeruginosa strains was screened for hypermutability, hypermutable phenotypes have been repeatedly observed in high proportion of CF infected patients indicating that this mechanism may play a crucial role in the pathogenesis of bacterial lung infection. Hypermutable strains may generate adaptive variants that confer a survival advantage to P. aeruginosa during chronic lung infection. To know which genes are involved in adaptation to lung the screening of a STM-library of P. aeruginosa mutants is currently in progress.
Data: CORDIS, © European Union
Project objective
Pseudomonas aeruginosa lung infection is the major cause of morbidity and mortality in Cystic Fibrosis (CF) patients. During chronic colonisation the persisting pathogen adapts to the CF niche due to the disease-specific environmental conditions of the hos t, such as anaerobic mucus layer and the pressure of innate immune defence system. Under those conditions P. aeruginosa evolves specific virulence mechanisms to evade the host defence and increases its fitness/survival. P. aeruginosa acquires adaptive muta tions becoming mucoid, resistant to antibiotics and may carry many others characters, which distinguish the late isolates strains from the initial colonising bacterium. Currently the onset of bacterial colonisation and changes in different phases of infect ion (from acute to chronic) are not completely understood. Although the process of bacterial airway colonisation has been investigated, its impact is restricted to a part of P. aeruginosa strains and insufficient to explain the pathogenicity. Here, we prop ose to use a signature-tagged transposen mutagenesis together with an analysis of P. aeruginosa genome sequence and differential gene expression to identify and characterise new genes involved in the chronic lung infection. A library of P. aeruginosa mutan ts will be constructed by random transposen insertional mutagenesis system and accomplished by tagging each mutant with a unique short DNA sequence so that it can subsequently be identified within a pool of mutants by DNA-DNA hybridization analysis. When a pplied to a chronic murine infection model for CF, mutants with an increased fitness/survival will be recovered from the lung after one week of infection and revealed by identification of the tags. The genomic DNA sequence flanking the transposen will allo w us to assign fimctions to inactivated genes and DNA array technology allow to characterise interaction with other genes. Further investigation on these candidate genes will be carried out #
Original text from CORDIS.
Participants
- FONDAZIONE CENTRO SAN RAFFAELE DEL MONTE TABOR · MILANOCoordinatorItaly
Links
Data: CORDIS, © European Union