INVESTIGADORES
LUJAN Adela Maria
congresos y reuniones científicas
Título:
Involvement of MutS in Pseudomonas aeruginosa adaptive mutagenesis: The acquisition of quorum-sensing-deficient (lasR) phenotype as an illustrative model
Autor/es:
LUJAN, ADELA M; MOYANO, ALEJANDRO J; ARGARAÑA CARLOS E; SMANIA, ANDREA M
Lugar:
Palma de Mallorca, España
Reunión:
Simposio; BActerial Adaptation Mechanims: Biofilms, Hypermutability and Antibiotic Resistance; 2007
Institución organizadora:
European Society of Clinical Microbiology and Infectious Diseases International Symposium
Resumen:
Pseudomonas aeruginosa mutator isolates are extremely frequent in Cystic Fibrosis (CF) chronic infections. Most of these mutator strains are found to be deficient in the mismatch repair system (MMR), with alterations in mutS predominating. It has been postulated that hypermutation plays an important role in P. aeruginosa adaptation to the CF lung and that they maybe selected in this stressful environment by hitchhiking with beneficial mutations. One of the most frequent beneficial alterations is a mutation inactivating lasR, which encodes a major regulator of the Quorum Sensing (QS) system, suggesting that loosing the invasive functions would be advantageous for P. aeruginosa persistence. In this context, we recently found that the emergence of QS-deficient (lasR) mutants is highly increased in a P. aeruginosa mutS strain, after cultivation in an aerated rich medium to late stationary-phase. LasR deficiency was due to simple but different point mutations along the lasR gene sequence. Interestingly, no sequence alterations were found in the gacA and rhlR genes, suggesting that the selective pressures for GacA/RhlR and LasR were not the same and differed from those in other Pseudomonas species, which, when incubated under the same conditions, show specific high instability in the gacA-gacS genes. Finally, we determined that a non-functional LasR would confer a selective advantage in the late stationary-phase, since viability was notably higher for lasR-negative mutants. Taken together, our results offer more evidences of the involvement of the MMR in the P. aeruginosa adaptive mutagenesis as well as in the accelerated emergence of CF-associated phenotypes. In this context, we are currently carrying out new investigations to elucidate which are the potential transcriptional regulators that could modulate the stationary-phase mutation rates in P. aeruginosa, a crucial issue in the genetic adaptation to the CF airway.