A Cyclic Dipeptide from Marine Fungus Penicillium chrysogenum 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 Chromobacterium violaceum CV026 and Pseudomonas aeruginosa PA01 has been isolated and purified from the crude extracts of the marine fungus Penicillium chrysogenum 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 C. violaceum CV026 by 79% and QS-mediated pyocyanin production, proteases, and elastase activity of P. aeruginosa PA01 by 41%, 20%, and 32%, respectively. In addition, it can also destroy the biofilm formation and decrease QS gene expression of P. aeruginosa 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 P. aeruginosa infections, and these findings could relieve the alarming problem of microbial resistance to antimicrobial drugs.

Cyclic Dipeptides: The Biological and Structural Landscape with Special Focus on the Anti-Cancer Proline-Based Scaffold

“…Additionally, Kumar et al reported the isolation of proline-containing DKPs, namely cyclo(D-Pro-L-Leu), cyclo(L-Pro-L-Met), cyclo(L-Pro-L-Phe), cyclo(D-Pro-L-Phe), cyclo(D-Phe-L-Pro), cyclo(D-Pro-D-Phe) and cyclo(L-Pro-D-Phe) isomers, as well as cyclo(L-Pro-L-Tyr), and cyclo(L-Pro-D-Tyr) from a culture filtrate of a Bacillus bacterial strain associated with an entomopathogenic nematode. These cyclic dipeptides showed significantly higher activity than the commercial fungicide bavistin against Fusarium oxysporum, Rhizoctonia solani, and Pencillium expansum [227,236,237]. Cyclo(L-Pro-L-Leu), cyclo(D-Pro-L-Leu), and cyclo(D-Pro-L-Tyr) displayed superior antifungal activity against Aspergillus flavus, Candida albicans, and F. oxysporum [41].…”

“…In another study, cyclo(L-Phe-L-Pro) produced by Vibrio vulnificus was found to activate the quorum sensing on an E. coli biosensor strain by modulating the expression of the gene encoding OmpU protein [231]. Finally, cyclo(L-Phe-L-Pro) and cyclo(L-Pro-L-Tyr) produced by Lactobacillus reuteri, were reported to interfere with quorum sensing in the Gram-positive S. Aureus [41,221,227,[232][233][234].…”

“…In regard to quorum sensing, proline-and hydroxyproline-based DKPs were found to influence cell-cell signaling, offering alternative ways of biofilm control by interfering with microbial communication [225][226][227][228][229]. Cyclo(L-Leu-L-Pro) and cyclo(L-Pro-L-Tyr) found in Pseudomonas putida, were able to activate the biosensor strain Agrobacterium tumefaciens NT1 [221,230].…”

Anti-Quorum-Sensing Activity of Tryptophan-Containing Cyclic Dipeptides

“…Numerous studies have shown that the expression of virulence factors for pathogenicity in P. aeruginosa is regulated by its QS system [14,15]. In the past few years, several known compounds, including some cyclic dipeptides, proved to exhibit anti-QS activity, such as chrysin, tyrosol, cyclo (L-Tyr-L-Pro) from Penicillium chrysogenum [16][17][18], cyclo (L-Trp-L-Ser) from Rheinheimera aquimaris [19], and cyclo (L-Phe-L-Pro) from Sphingomonas sp. WG [20].…”

Diketopiperazine Gels: New Horizons from the Self-Assembly of Cyclic Dipeptides

“…CDPs are indeed attracting interest as drug carriers, thanks to their demonstrated ability to cross membranes and penetrate cells [ 29 ]. Their aggregates can display fluorescence [ 30 ], and they are widely studied for their diverse biological activities [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ], which make them promising for biomedical applications, as recently reviewed [ 39 ]. Further, they are being investigated also for optoelectronic [ 40 ] and catalytic [ 41 ] applications, as biodegradable and environmentally-friendly substitutes of more traditional options.…”