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Nadia Abed

The Fur protein, a new antibacterial target? Approach using peptide aptamers

Published on 30 March 2005


Thesis presented March 30, 2005

Abstract:
The identification of new antibacterial targets seems to be a crucial point to struggle against multiresistant strains. The link between iron bio-availability and virulence is now well established. Thus, the inhibition of the Ferric Uptake Regulation protein (Fur), a global regulator present in most of bacteria could be a very interesting target. The major activity of Fur has been established as a transcriptional regulator of many genes related with iron metabolism and oxidative stress. With the aim to confirm this hypothesis, we have chosen to select proteins able to inhibit the protein Fur in  vivo using Peptide aptamers (artificial biomolecules) able to recognize and inhibit specific protein targets. First, we have selected in vivo using E. coli, aptamers able to generate a phenotype characteristic of fur mutant, resistant of high concentration of Mn2+. Among the selected aptamers, two of them seem to be of particular interest, Mn1 and Mn2 and a detailed study of their activity showed that they were implicated in both iron metabolism and oxidative stress regulation. Nevertheless, we have shown that the target of these aptamers wasn’t the protein Fur. In a second case, aptamers able to interact with the protein Fur have been isolated using the yeast two-hybrid technology. Therefore, we have selected 4 aptamers (F1 to F4) that interact and inhibit Fur in different ways. Their characterization allowed us to suggest a mechanism of action for each of them and to get more information about the protein Fur activity.

Keywords:
Fur, peptide aptamers, iron, oxidative​ stress, bacteria, two hybrid, manganese resistance

Download this thesis (Intranet link).