Abstract
A constant search for new molecular targets is required due to the widespread evolution of antibiotic resistance and multi-resistance among bacterial infections. For many years, it has been thought that an effective drug intervention method would be to inhibit the enzymes that catalyze certain stage of bacterial amino-acid production. The bacterial metalloenzyme histidinol dehydrogenase (HDH, EC 1.1.1.23) catalyzes the two final steps of l-histidine biosynthesis and is crucial for the intramacrophagic replication of the facultative intracellular pathogens such as Brucella suis and Mycobacterium tuberculosis. Targeting of this virulence factor has opened up new opportunities for the design and synthesis of innovative anti-infective drugs. This chapter basically provides a current summary of the critical role played by this enzyme in intracellular bacteria, addressing the various strategies investigated to find selective inhibitors.
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