KSEF RDE: S. aureus Inorganic Pyrophosphatase, a Potential Target for Novel Antimicrobials

S. aureus inorganic pyrophosphatase, a potential target for novel antimicrobials The World Health Organization has identified antimicrobial resistance as one of the top three threats to human health. In contrast with the fast evolution and spreading of drug-resistant pathogens, the number of effective antimicrobials that are available to healthcare workers is dwindling. Staphylococcus aureus is one of the five most common causes of nosocomial infections and is often the cause of postsurgical wound infections. S. aureus infections lead to life-threatening diseases such as pneumonia, meningitis, osteomyelitis, endocarditis, and sepsis. S. aureus is notorious for its ability to become resistant to antibiotics. The long-term goal of our research is to find solutions to treat bacterial infections caused by drug resistant pathogens, and the objective of the proposed study is to validate and develop a novel antimicrobial target, S. aureus Family II Inorganic Pyrophosphatase, which is an essential enzyme for the survival of the pathogen. Pyrophosphatase (PPase) catalyzes the hydrolysis of pyrophosphate and provides a thermodynamic pull for many biosynthetic reactions and therefore is an essential enzyme for all kingdoms of life. In this study we will 1) characterize this novel enzyme, and 2) validate and optimize activity-based assays to identify inhibitora that interfere with its activity. Outcomes from the proposed research include the establishment of a novel anti-microbial target and advancement of knowledge on the structure and functional mechanism of PPases, a class of critical enzymes for all living organisms. Key words: Staphylococcus aureus, inorganic pyrophosphatase, inhibitor, assay, protein structure and function Additional 5: Pyrophosphatase, Protein biophysics, enzymology, metalloprotein, antimicrobial resistance