Bacterial Pyruvate Kinase: A New Potential Target to Combat Drug‐Resistant Staphylococcus aureus Infections

Abstract

AbstractSeverity of Infections caused by Staphylococcus aureus ranges from trivial to spine chilling. Irrespective of multiple drugs availability to treat S. aureus infections, increase in drug‐resistance has led to the continuous emergence of resistant strains of all S. aureus including MRSA. Hence, there is an urgent unmet need for novel antibacterial agents to combat multi drug resistant infections which act through unexploited targets/mechanism. Bacterial pyruvate kinase (PK) is one such unique cytoplasmic enzyme crucial in carbohydrate metabolism. It exists in several microorganisms including Mycobacterium sp, P. falciparaum, T. gondii, L. mexicana, V. cholera, etc. In MRSA, PK is an important hub in protein‐protein network with more than 200 interacting partners in a large‐scale protein interaction analysis and might be less susceptible to genetic mutation and resistance due to the network centrality‐lethality criteria. Methicillin resistant S. aureus pyruvate kinase (SAPK) antisense and knockout tests revealed that it is required for growth of MRSA. In recent times, PKs gained attention as potential new targets to combat trypanosomal, leishmanial, malarial and viral infections. This review provides valuable insights about indole alkaloids from natural products and synthetic SAPK inhibitors along with their inhibitory properties against S. aureus and MRSA strains. This review also describes essential structural features and Structure‐Activity Relationship (SAR) for SAPK inhibition.