Kaempferol and Kaempferin Alleviate MRSA Virulence by Suppressing β-Lactamase and Inflammation

Methicillin-resistant <i>S. aureus</i> (MRSA) possesses broad resistance, biofilm formation, and high virulence characteristics. Therefore, developing new therapeutic strategies against this pathogen is urgent. This work reports kaempferol (kol) and kaempferin (kin) bound to the active site of β-lactamase and interacting with key residues, thereby inhibiting its activity. In addition, kol and kin reduced the secretion of β-lactamase to the external environment, then the shielding effect of β-lactamase to β-lactam antibiotics was weakened, and finally, the bactericidal ability of ampicillin (Amp) to MRSA was enhanced. Kol and kin relieved the inflammatory responses of J774 cells induced by MRSA and improved the survival of <i>Galleria mellonella</i> (<i>G. mellonella</i>) infected by MRSA when combined with or without Amp. These data suggest that kol and kin have the potential to be developed as anti-MRSA infection agents, which would broaden the application prospects of these compounds.