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Chemical composition and disruption of quorum sensing signaling in geographically diverse United States propolis.

ABSTRACT: Propolis or bee glue has been used for centuries for various purposes and is especially important in human health due to many of its biological and pharmacological properties. In this work we showed quorum sensing inhibitory (QSI) activity of ten geographically distinct propolis samples from the United States using the acyl-homoserine lactone- (AHL-) dependent Chromobacterium violaceum strain CV026. Based on GC-MS chemical profiling the propolis samples can be classified into several groups that are as follows: (1) rich in cinnamic acid derivatives, (2) rich in flavonoids, and (3) rich in triterpenes. An in-depth analysis of the propolis from North Carolina led to the isolation and identification of a triterpenic acid that was recently isolated from Hondurian propolis (Central America) and ethyl ether of p-coumaric alcohol not previously identified in bee propolis. QSI activity was also observed in the second group US propolis samples which contained the flavonoid pinocembrin in addition to other flavonoid compounds. The discovery of compounds that are involved in QSI activity has the potential to facilitate studies that may lead to the development of antivirulence therapies that can be complementary and/or alternative treatments against antibiotic resistant bacterial pathogens and/or emerging pathogens that have yet to be identified.

SUBMITTER: Savka MA

PROVIDER: S-EPMC4413979 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Resistance to antibiotics is a critical growing public health problem that desires urgent action to combat. To avoid the stress on bacterial growth that evokes the resistance development, anti-virulence agents can be an attractive strategy as they do not target bacterial growth. Quorum sensing (QS) systems play main roles in controlling the production of diverse virulence factors and biofilm formation in bacteria. Thus, interfering with QS systems could result in mitigation of the bacterial virulence. Cilostazol is an antiplatelet and a vasodilator FDA approved drug. This study aimed to evaluate the anti-virulence activities of cilostazol in the light of its possible interference with QS systems in Pseudomonas aeruginosa. Additionally, the study examines cilostazol's impact on the bacterium's ability to induce infection in vivo, using sub-inhibitory concentrations to minimize the risk of resistance development. In this context, the biofilm formation, the production of virulence factors and influence on the in vivo ability to induce infection were assessed in the presence of cilostazol at sub-inhibitory concentration. Furthermore, the outcome of combination with antibiotics was evaluated. Cilostazol interfered with biofilm formation in P. aeruginosa. Moreover, swarming motility, biofilm formation and production of virulence factors were significantly diminished. Histopathological investigation revealed that liver, spleen and kidney tissues damage was abolished in mice injected with cilostazol-treated bacteria. Cilostazol exhibited a synergistic outcome when used in combination with antibiotics. At the molecular level, cilostazol downregulated the QS genes and showed considerable affinity to QS receptors. In conclusion, Cilostazol could be used as adjunct therapy with antibiotics for treating Pseudomonal infections. This research highlights cilostazol's potential to combat bacterial infections by targeting virulence mechanisms, reducing the risk of antibiotic resistance, and enhancing treatment efficacy against P. aeruginosa. These findings open avenues for repurposing existing drugs, offering new, safer, and more effective infection control strategies.

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Chemical composition and disruption of quorum sensing signaling in geographically diverse United States propolis.

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