Butenolide, a Marine-Derived Broad-Spectrum Antibiofilm Agent Against Both Gram-Positive and Gram-Negative Pathogenic Bacteria

Bacterial biofilm can cause nosocomial recurrent infections and implanted device secondary infections in patients and strongly promotes development of pathogenic drug resistance in clinical treatments. Butenolide is an effective anti-macrofouling compound derived from a marine Streptomyces sp., but its antibiofilm efficacy remains largely unexplored. In the present study, the antibiofilm activities of butenolide were examined using biofilms formed by both Gram-positive and Gram-negative pathogenic model species. Four Escherichia coli strains, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus (MRSA) were used as targets in antibiofilm assays that examined the effects of butenolide, including the following: (i) on bacterial growth; (ii) in inhibiting biofilm formation and eradicating mature biofilm; (iii) on biofilm structures. In addition, the synergistic effect between butenolide with tetracycline was also examined. Butenolide not only effectively inhibited the biofilm formation but also eradicated pre-formed biofilms of tested bacteria. Fractional inhibitory concentration index (FICI) indicated that butenolide was a potential tetracycline enhancer against E. coli, P. aeruginosa, and MRSA. These results indicated that butenolide may hold a great potential as an effective antibiofilm agent to control and prevent biofilm-associated infections in future clinical treatments.