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Molecular mechanisms of resistance, virulence and epidemicity in Streptococcus pneumoniae. PREVIS (Pneumococcal Resistance Epidemicity and Virulence - an international study


Human pathogens face two main kinds of evolutionary challenges. A. Survival and growth in an antibiotic rich milieu selects for genetic traits of resistance. B. Successful drug resistant strains must also be able to compete with other members of the species for colonization, spread and disease in the host. The main purpose is to examine the interplay of these two - as well as host and environmental - factors. Streptococcus pneumoniae (SP) remains among the most important causes of life-threatening community-acquired diseases. Drug resistantpneumococcal clones (DRPn) emerging from a major ecological reservoir (healthy children in Day-care centres) are widely spread in Europe threatening effective antibiotic therapy. Our multidisciplinary expertise of collaborating centres will identify bacterial genetic determinants and host factors associated with invasive disease, DRPn and spread of epidemic SP clones. The project will focus on
(a) frequency and clonal types of drug resistant and drug susceptible SP causing invasive disease and found among healthy carriers, to study disease potential and transmission dynamics;
(b) genetic determinants of virulence and resistance using comparative genomics and transcriptional profiling involving DNA microarrays based on sequenced genomes;
(c) sequencing of S. mitis, a frequent source of genes and gene fragments resulting in SP resistance;
(d) the ability of antibiotic resistance determinants to affect pathogen-host interactions and identification of host factors;
(e) novel approaches to develop anti-virulence drugs
f) the threshold level of antibiotic consumption in the community that selects for resistance;
g) integrating data by development of a web-based data management infrastructure coupled with advanced machine learning tools for automated data-mining of predictive associations.

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Nobels väg 18

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Participants (11)