Mode of action of Elasnin as biofilm-formation eradicator of Methicillin-Resistant Staphylococcus aureus

Abstract

\n Biofilm is made by microbes and often offers protection by making them more tolerant, resistant, and resilient to wide-range antimicrobials. Biofilm-related infections account for more than 80% of human bacterial infections and are especially prevalent in chronic tissue and device-related infections. Owing to the great challenge in treating biofilms, novel and effective antibiofilm compounds urgently need to be identified. We herein identified elasnin as a potent biofilm-targeting compound against methicillin-resistant Staphylococcus aureus (MRSA) through bioassay-guided isolation of bioactive compounds from Actinobacteria. Elasnin effectively inhibited biofilm formation and eradicated pre-formed biofilms of MRSA, and it displays low cytotoxicity with a low risk of resistance development. Transcriptomic and proteomic analyses combined with confocal microscopy observation revealed that elasnin destroyed the biofilm matrix in a time-dependent manner and interfered with cell cycle during the exponential phase, primarily by repressing the expression of virulence factors. Moreover, the biofilm cells released from elasnin treatment showed increased sensitivity to penicillin G. Overall, this study identified elasnin as a promising biofilm-eradicating compound against MRSA and shed light on its action mechanism.