Biofilms are surface-attached multicellular communities that play critical roles in inducing biofouling and biocorrosion in the marine environment. Given the serious economic losses and problems caused by biofouling and biocorrosion, effective biofilm control strategies are highly sought after. In a screening program of antibiofilm compounds against marine biofilms, we discovered the potent biofilm inhibitory activity of elasnin. Elasnin effectively inhibited the biofilm formation of seven strains of bacteria isolated from marine biofilms. With high productivity, elasnin-based coatings were prepared in an easy and cost-effective way, which exhibited great performance in inhibiting the formation of multi-species biofilms and the attachment of large biofouling organisms in the marine environment. The 16S amplicon analysis and anti-larvae assay revealed that elasnin could prevent biofouling by the indirect impact of changed microbial composition of biofilms and direct inhibitory effect on larval settlement with low toxic effects. These findings indicated the potential application of elasnin in biofilm and biofouling control in the marine environment.

Biofilms are surface-attached multicellular communities that create many problems in human health and various industries. Given the prominence of biofilms in biofouling and infectious diseases, antibiofilm control approaches are highly sought after. In the present study, we identified elasnin as a potent antibiofilm agent through a bioassay-guided approach. Elasnin specifically inhibited the biofilm formation of bacterial mono-species and eradicated the mature biofilm of Gram-positive bacteria at concentrations below 2.5 μg/mL with a low toxic effect on cells and a low resistance risk. Confocal observations illustrated that elasnin decreased cell aggregations and destroyed the biofilm matrix. Furthermore, elasnin-based antibiofilm coatings were prepared and inhibited the formation of multi-species biofilms and the attachment of large biofouling organisms in the field test. These findings suggest that elasnin is a promising antibiofilm agent for future applications in biofilm control. Importance: Due to the increased diversity of biofilm-associated infections and the failure of conventional antimicrobial treatment, new and effective biofilm-specific pharmacologic strategies are urgently needed. Elasnin is a new antibiofilm natural product produced by Streptomyces with high efficiency and low toxicity. Elasnin effectively destroyed the biofilm matrix of Gram-positive bacteria, thus making them more susceptible to antibiotics. Unlike currently deployed antibiotic vancomycin, which exclusively targets essential life processes and kills the pathogen, elasnin did not exhibit bactericidal effect and thus held great potential in delaying resistance. With high yield, elasnin-based coatings were easily prepared with low expenditures and exhibited favorable performance in field test. Collectively, the antibiofilm properties of elasnin, combined with the low cost of supply and the low risk of resistance, could provide the basis for the development of a novel antibiofilm agent that could help fight to antibiotics resistance.

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.