Résumé
The widespread emergence of resistance and multi-resistance to antibiotics among bacterial pathogens represents a major threat and necessitates a permanent race for finding new molecular targets. Inhibition of enzymes catalyzing particular steps of bacterial amino acid biosynthesis has been considered for several years as a pertinent strategy for drug intervention. Identification of specific inhibitors of the original target histidinol dehydrogenase (HDH, EC 1.1.1.23), the bacterial metalloenzyme responsible for the catalysis of the last step of l-histidine biosynthesis, has opened new opportunities for the development of novel anti-infective agents. This chapter gives an up-to-date overview of the role played by this crucial enzyme in intracellular bacteria and describes the different approaches explored to identify inhibitors of this metalloprotein with potential application as novel antimicrobial drugs.