Ribonucleotide Reductases catalize the reduction of ribonucleotides to deoxyribonucleotides providing the building blocks for DNA synthesis. Up to date, they are classified into threee different classes: aerobic class I (further subdivided into class Ia and Ib), class II (which is active either in the presence or absence of oxygen), and the anaerobic class III. \i Salmonella typhimurium\i0 and several bacteria have the coding potential for two class I enzymes; class Ia, which is physiologically active, and the Ib enzyme, with no obvious finction. Moreover, \i Sal monella\i0 harbours a class III enzyme, which bears its anaerobic growth. So far, any biological function has been gien to the RNR class Ib in order to justify its coexistence with other enzymes in one single bacterium. Severak experimental evidences support the idea that all three RNR can be differentially expressed during a pathogenic process. The main goal of this project is to characterize molecular mechanisms involved inthe genetic regulation of each class and to elucidate their role during pathogenesis. In order to accomplish our goals we shall analyze the expression of these genes under the control of iron (Fur) and oxygen (Fur/Arc) transcriptional regulators as well as under the control of any other uncharacterized regulator. The role of each class during pathogenesis will be studied by working with defective mutants in one ot two enzymes at the same time, and by comparing variations in infectivity, survival and persistence inside the host. Finally, we attempt to carry out the molecular and genetic analysis of the RNR found in the pathogenic bacteria \i Streptococcus pyogenes and Pseudomonas aeruginosa.\i0 This analysis will allow us to establish the molecular basis to comprehend the mechanisms that regulate the different RNR within each one of these organisms
|Effective start/end date||28/12/01 → 27/12/04|
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.