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FRIMEDBIO-Fri prosj.st. med.,helse,biol

Regulation of competence for natural transformation in Streptococcus pneumoniae

Tildelt: kr 3,4 mill.

Bacteria that have the ability to take up naked DNA from the environment and incorporate this DNA into their genomes by homologous recombination are said to be naturally competent for genetic transformation. About 70 species of bacteria have been reported to possess this property. One of the best studied is the important human pathogen Streptococcus pneumoniae, which has served as a model organism for studies on various aspects of this phenomenon. In S. pneumoniae and related streptococci, acquisition of DNA by natural transformation contributes strongly to intraspecies as well as interspecies gene exchange. Such lateral gene transfer will occasionally give rise to antibiotic resistance, increased virulence and serotype conversion in the pneumococcal reci pient, and the phenomenon is therefore of great clinical significance. In addition, pneumococcal mutants that have lost the ability to develop the competent state are attenuated in virulence. The main objectives of the present project is to gain increased insight into the mechanisms, that in addition to and in conjunction with the ComABCDE quorum-sensing system, regulate competence development in S. pneumoniae. Identification of the physico-chemical factors stimulating or inhibiting competence development in vitro will help us understand where and under which circumstances the competence state is turned on in the human body. By using real-time biophotonic imaging we will also study development of the competent state in vivo in a mouse model.To be able to determine the conditions under which the competent state is induced in the human host, the factors governing expression of the comABCDE genes must be identified and the role of the CiaRH and StkP regulatory systems must be elucidated. Undoubtedly, increa sed insight into these matters will be important for future improvements of therapeutic strategies and development of countermeasures aimed at reducing the spread of hazardous traits.

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FRIMEDBIO-Fri prosj.st. med.,helse,biol

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