Unravelling structure and mechanism of adenine(22)-tRNA methyltransferase: towards novel antibiotics against MRSA

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of hospital infections worldwide. This bacterium has been found to cause infections in otherwise healthy communities whereas it used to be restricted to healthcare facilities. MRSA isolates have emerged that are resistant to most antibiotics in clinical use. It is imperative that new drugs are developed to combat MRSA. It is easier to develop specific antibiotics when bacterial molecules are well understood. A drug could be developed that inhibits an enzyme essential for MRSA growth will stop infections.

The enzyme N1-adenine(22)-tRNA methyltransferase (TrmK) is essential in MRSA and absent in humans but we know little about its structure and function. In this project, we will elucidate the mechanism of action of TrmK using enzyme kinetics and crystallography.

Our results will pave the way for follow-up work to create specific inhibitors to be further developed into drugs that can treat MRSA infection.