Multifaceted Antipathogenic Activity of Two Novel Natural Products, Chermesiterpenoid B and Chermesiterpenoid B Seco Acid Methyl Ester, Against Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic human pathogen that causes both acute and chronic infections due to its virulence factors, biofilm formation and the ability to suppress the host immune system. Quorum sensing (QS) plays a key role in regulating these pathogenic traits and also downregulates the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) in host cells. In this study, we isolated two novel natural products from the jellyfish-derived fungus Penicillium chermesinum, chermesiterpenoid B (Che B) seco acid methyl ester (Che B ester) and Che B. Both compounds act as partial agonists of PPAR-γ and exhibit anti-QS activity. Che B ester and Che B were found to inhibit biofilm formation, reduce the production of proteases and decrease the infectivity of P. aeruginosa, all without affecting bacterial growth. In host cells, Che B ester and Che B reduced P. aeruginosa-induced inflammation by activating PPAR-γ. This multifaceted function makes these compounds promising candidates for developing new antipathogenic agents against bacterial infections with few side effects.