Dehydrozaluzanin C, a novel type of anti-bacterial agent which targets transporting proteins, Opp and OpuC

Abstract

The evolution and widespread distribution of antibiotic-resistance elements in bacterial pathogens is eroding our ability to control infections with antibiotics. Unfortunately,there was a failure in antibacterial drug discovery with the rise in global resistance. In the post-antibiotic era, patients may die from ordinary infections because diseases that were once easily treatable have been deadly again due to a lack of effective antibiotics. Therefore, novel antibacterial medicines that are able to control infection in the resistance era are urgently required. Here we used Staphylococcus aureus (S.aureus) to identify a natural product 5-29 (Dehydrozaluzanin C), which blocks transport channels of nutrients or signaling molecules and osmoprotectants by binding to the oligopeptide permease OppB, OppC, OppD and osmoprotectant uptake OpuCB, OpuCD in G + bacteria methicillin-resistant staphylococcus aureus (MRSA). In the murine MRSA infection model, 5-29 blocked infection with the lowest dose of 4 mg/Kg rather than vancomycin(40 mg/Kg). This promising antibiotic compound suggests that discovery of natural products isolated from traditional medicine can be taken as a potential approach to targeting Opp and Opu transport systems for challenging bacterial pathogens.