A novel indolylbenzoquinone compound HL-J6 suppresses biofilm formation and -toxin secretion in methicillin-resistant Staphylococcus aureus

Eradication of methicillin-resistant Staphylococcus aureus (MRSA) is challenging due to multi-drug resistance of strains and biofilm formation, the latter of which is an important barrier to the penetration of antibiotics and host defences. As such, there is an urgent need to discover and develop novel agents to fight MRSA-associated infection. In this study, HL-J6, a novel indolylbenzoquinone compound, was shown to inhibit S. aureus strains, with a minimum inhibitory concentration against MRSA252 of 2 mu g/mL. Moreover, HL-J6 exhibited potent antibiofilm activity in vitro and was able to kill bacteria in biofilm. In the mouse models of wound infection, HL-J6 treatment reduced the MRSA load significantly and inhibited biofilm formation on the wounds. The potent targets of its antibiofilm activity were explored by realtime reverse transcriptase polymerase chain rection, which indicated that HL-J6 downregulated the transcription levels of sarA, atlAE and icaADBC . Moreover, Western blot results showed that HL-J6 reduced the secretion level of alpha-toxin, a major virulence factor. These findings indicate that HL-J6 is a promising lead compound for the development of novel drugs against MRSA biofilm infections.(c) 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.