A Cyclic Dipeptide from Marine Fungus <i>Penicillium chrysogenum</i> DXY-1 Exhibits Anti-quorum Sensing Activity

Abstract

Bacterial quorum sensing (QS) is anticipated as a new potential target for the development of antimicrobial drugs. An anti-QS substance against <i>Chromobacterium violaceum</i> CV026 and <i>Pseudomonas aeruginosa</i> PA01 has been isolated and purified from the crude extracts of the marine fungus <i>Penicillium chrysogenum</i> DXY-1, and the accurate structure was identified as cyclo(l-Tyr-l-Pro). This cyclic dipeptide at sub-minimum inhibitory concentration can decrease the QS-regulated violacein production of <i>C. violaceum</i> CV026 by 79% and QS-mediated pyocyanin production, proteases, and elastase activity of <i>P. aeruginosa</i> PA01 by 41%, 20%, and 32%, respectively. In addition, it can also destroy the biofilm formation and decrease QS gene expression of <i>P. aeruginosa</i> PA01. Molecular docking was further performed, and the obtained data indicated that this dipeptide blocks the effect of QS autoinducers through competitive binding to the same pocket of the receptor proteins. We expect this anti-QS cyclic dipeptide to be a potential pro-drug treating drug-resistant <i>P. aeruginosa</i> infections, and these findings could relieve the alarming problem of microbial resistance to antimicrobial drugs.