Identification of Novel Cyclohexene Derivatives With Antibiofilm and Antivirulence Effects From Streptomyces tirandamycinicus ZSA11.

Pseudomonas aeruginosa is a Gram-negative pathogen whose biofilm-associated antibiotic tolerance poses severe treatment challenges. In this study, we discovered that organic crude extracts from Streptomyces tirandamycinicus ZSA11 exhibit significant inhibition of biofilm formation by P. aeruginosa PAO1 without cytotoxicity. Chemical analysis of these active extracts identified three cyclohexene derivatives, including compound 3, which is a novel compound. The structures of these compounds were elucidated through HRESIMS, NMR spectroscopy, and x-ray diffraction. Further findings suggest that all of these cyclohexene derivatives inhibit the biofilm formation of PAO1 by reducing intracellular c-di-GMP levels and repressing quorum-sensing systems. Moreover, PAO1 treated with these derivatives showed a significant decrease in pyocyanin production and total exoprotease activity, suggesting their potential for antivirulence. These findings underscore the promise of S. tirandamycinicus ZSA11 extracts and cyclohexene derivatives as candidates for treating biofilm-associated infections caused by antibiotic-resistant pathogens.