Function and regulation of virulence-related genes of the proteobacterium Pseudomonas aeruginosa

Abstract

Pseudomonas aeruginosa is a gamma-proteobacterium often found in soil and water that behaves as an opportunistic pathogen. In humans, it is one of the leading causes of nosocomial infections and colonizes burns, surgical wounds and the lungs of cystic fibrosis patients. In those patients, P. aeruginosa causes a severe inflammatory reaction that often leads to lung failure and death. P. aeruginosa pathogenicity has been extensively studied regarding the factors directly responsible for virulence, such as toxins, extracellular enzymes and secretion systems, as well as its high intrinsic resistance to antibiotics. It is a model organism for research on phenomena such as cell-cell communication, biofilm formation, gene expression, metabolism and also for studies on bacterial diversity and genetic variability. The main goal of this project is to characterize genes related to P. aeruginosa pathogenicity, regarding their expression and the function of their products, both in traits unique to PA14 as in aspects conserved in a broad range of pathogenic bacteria. The specific aims include functional studies of the putative methyltransferase KerV and its connection to quorum sensing and secretion of virulence factors; the screening for protein-protein interactions between products of genes conserved in genomic islands; the detailing of the studies on regulation of expression of genes present in PA14 pathogenicity island, as well as the search for targets of the c-di-GMP phosphodiesterase PvrR. For the achievement of these aims, we will use genetic, biochemical and molecular biology approaches. This work is already in progress, as a development of a Jovem Pesquisador grant that will end in July, 2009. (AU)