INESC-ID   Instituto de Engenharia de Sistemas e Computadores Investigação e Desenvolvimento em Lisboa
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Knowledge Discovery and Bioinformatics
Inesc-ID Lisboa

Understanding the mechanisms of virulence and resistance

01/18/2013 - 11:00
01/18/2013 - 12:00

Infectious diseases remain among the major causes of human death in the world. Several infections at hospitals are due to opportunistic pathogens, microorganisms that rarely infect healthy people, but are a frequent cause of infection in people with basal diseases, who are immunodepressed or debilitated. Environmental bacteria, frequently antibiotic resistant, constitute a large percentage of those pathogens. Our work focuses on understanding the mechanisms of virulence and resistance, as well as possible crosstalk, of these pathogens. Within this scope, in the last two years, we have been defining those genes whose mutation changes the phenotype of antibiotic susceptibility. As a result, we have selected nearly three hundred genes for future analysis and are currently studying whether those mutations that challenge intrinsic resistance also alter the virulence of Pseudomonas aeruginosa and Stenotrophomonas maltophilia. We found that mutations in several genes encoding proteins from different categories that include multidrug efflux pumps, two component systems, metabolic enzymes or global regulators, simultaneously alter the antibiotic susceptibility and the virulence of P. aeruginosa. Another opportunistic pathogen we are working with is S. maltophilia, which is characterized by its intrinsic low susceptibility to several antibiotics. Part of this low susceptibility relies on the expression of chromosomally-encoded multidrug efflux pumps. Including this, the metagenome approach infers new pathways to explain the transmission of antibiotic enconded genes caused by horizontal gene transfer.