Characterisation of the bacterial GTPase Obg, a novel target for drug development

Samenvatting

Persisters consists of subpopulation of cells showing tolerance in presence of high doses of bactericidal antibiotics. Recent studies pointed out the importance of persistence in chronic infections, yet the persistence model needs to be further clarified. The universally conserved bacterial GTPase Obg, seems to have a central role in persistence regulation. Acting as an intracellular sensor for GTP levels. Here we show the expression, purification and characterization of different mutations predicted to be involved in persistence and hydroxiurea sensitivity. We found in the mutant constructs an overall lower affinity for GDP and GTP, compared to the wt. A rather lower activity has also been detected for the mutants involved in hydroxyurea sensivity. However from the results there seems to be no clear relationship between the nucleotide affinity and the persistence phenotype.

Datum prijs	2 sep. 2014
Originele taal	English
Begeleider	Wim Versées (Promotor)