Antibiofilm Efficacy and Mechanism of the Marine Chlorinated Indole Sesquiterpene Against Methicillin-Resistant Staphylococcus aureus .

Methicillin-resistant Staphylococcus aureus (MRSA) can easily form biofilms on food surfaces, thus leading to cross-contamination, which is difficult to remove. Therefore, there is an urgent need to find alternatives with good antibacterial and antibiofilm effects. In this study, two indole sesquiterpene compounds, xiamycin ( 1 ) and chlorinated metabolite chloroxiamycin ( 2 ), were isolated from the fermentation liquid of marine Streptomyces sp. NBU3429 for the first time. The chemical structures of the two compounds were characterized by spectroscopic data interpretation, including 1D NMR and HRESIMS analysis. Antimicrobial test showed that chloroxiamycin ( 2 ) (minimum inhibitory concentration, MIC = 16 μg/mL) exhibited superior antibacterial activity than xiamycin ( 1 ) (MIC = 32 μg/mL) against MRSA ATCC43300. Moreover, compound ( 2 ) decreased the biofilm formation rate of MRSA ATCC43300 by 12.7%-84.6% in the concentration range of 32-512 μg/mL, which is relatively stronger than xiamycin ( 1 ) (4.1%-49.9%) as well. Antibacterial/antibiofilm mechanism investigation indicated that chloroxiamycin ( 2 ) could disrupt the cell wall and membrane of MRSA, inhibiting the production of biofilm extracellular polysaccharides. All these results illustrated that chloroxiamycin ( 2 ) is an effective antibacterial/antibiofilm agent, which makes it an attractive candidate for food preservatives.