Targeting Cyclic di-AMP Signaling through Diadenylate Cyclase Inhibition Reduces Methicillin Resistance in Clinical MRSA Isolates
HIGHLIGHT • Cyclic-di-AMP is a non-canonical driver of methicillin resistance in MRSA • Sub-MIC methicillin and biofilms elevate c-di-AMP via DacA upregulation • Elevated c-di-AMP activates STING and skews macrophage responses • FDA approved drugs Tropinone and eucalyptol identified as DacA inhibitors • DacA inhibition restores β-lactam susceptibility in MRSA