Pyrimirhodomyrtone inhibits Staphylococcus aureus by affecting the activity of NagA

Abstract

The epidemic of methicillin-resistant Staphylococcus aureus (MRSA) infections has created a critical health threat. The drug resistance of MRSA makes the development of drugs with new modes of action particularly urgent. In this study, we found that a natural product derivative pyrimirhodomyrtone (PRM) exerted antibacterial activity against S. aureus, including MRSA, both in vitro and in vivo. Genetic and biochemical studies revealed the interaction between PRM and N-acetylglucosamine-6-phosphate deacetylase (NagA) and the inhibitory effect of PRM on its deacetylation activity. We also found that PRM causes depolarization and destroys the integrity of the cell membrane. The elucidation of the antibacterial mechanism will inspire the subsequent development of new anti-MRSA drugs based on PRM.

Keywords: Anti-MRSA activity; N-acetylglucosamine-6-phosphate deacetylase; NagA; Phloroglucinol derivative; Pyrimirhodomyrtone; Staphylococcus aureus.