Drug Target Validation in Polyamine Metabolism and Drug Discovery Advancements to Combat Actinobacterial Infectious Diseases

Actinobacterial natural ecological niches are characterized by variations in the availability of nutrients, resulting in a complex metabolism. Their remarkable ability to adapt to fluctuating nutrient conditions is possible through the utilization of large amounts of substrates. Recent discoveries in bacterial metabolism suggested the importance of polyamine metabolism in bacteria, particularly in those of the order Actinomycetales, to survive in their natural habitats. This makes such enzymes promising targets to inhibit their growth. Since the polyamine metabolism of soil bacteria of the genus Streptomyces and the human pathogenic Mycobacteria is surprisingly similar, a target-based drug development in Streptomyces and Mycobacterium spp. is an alternative approach to the classical search of antibiotics. The recent development of drugs to treat epidemic diseases like tuberculosis (TB) has gained attention due to the occurrence of multi-drug-resistant strains. In addition, drug repurposing plays a crucial role in the treatment of various complex diseases, such as malaria. With that notion, the treatment of TB could also benefit from this approach. For example, molecular chaperones, proteins that help other proteins to fold properly are found in almost all living organisms including the causative agents of TB. Therefore, targeting these molecules could help in the treatment of TB. We aim to summarize the knowledge of nitrogen and carbon metabolism of the two closely related actinobacterial genera, Streptomyces and Mycobacterium, and of the identification of new potential drug targets.