Comparative Evaluation of Combinatory Interaction between Endocannabinoid System Compounds and Poly-L-lysine against Streptococcus mutans Growth and Biofilm Formation.

Mark Feldman,Isaac Ginsburg,Ronit Sionov,Doron Steinberg,Reem Smoum,Raphael Mechoulam

doi:10.1155/2020/7258380

Mark Feldman, Isaac Ginsburg

Open Access

https://doi.org/10.1155/2020/7258380

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Journal: BioMed research international	Publication Date: Jan 31, 2020
Citations: 12	License type: CC BY 4.0

Affiliation: Hebrew University of Jerusalem

Abstract

Endocannabinoid/endocannabinoid-like (EC/EC-like) are natural endogenous compounds which have been found to affect MRSA pathogenicity. Our previous studies showed that EC/EC-like was able to impair staphylococcal biofilm formation and maintenance as well as to alter biofilm-associated virulence factors. In the present study, we investigated the combinatory effect of the selected EC/EC-like with a natural antimicrobial agent, poly-L-lysine, on cariogenic bacteria Streptococcus mutans growth and biofilm formation. Among four tested EC/EC-like, only two, anandamide (AEA) and oleoylethanolamide (OEA), exhibited synergistic combinatory effect with poly-L-lysine against S. mutans. We attribute this distinct effect to differences in the fatty acid chain structure of the selected EC/EC-like compounds. Moreover, AEA exerted a specific antibiofilm mode of action against S. mutans by effecting total inhibition of biofilm formation while still allowing bacteria viability. Finally, we postulate that the presence of EC/EC-like and poly-L-lysine could enhance the permeability and efficacy of each other via hydrophobic and electrostatic interactions with the S. mutans membrane. In conclusion, we assume that a combination of endogenous natural compounds such as EC/EC-like and poly-L-lysine may benefit oral hygiene by preventing dental plaque.

Highlights

Endocannabinoid/endocannabinoid-like (EC/EC-like) are natural endogenous compounds which have been found to affect MRSA pathogenicity
E endocannabinoid system (ECS) is composed of endocannabinoids (ECs) and enzymes responsible for the synthesis and degradation of the EC, as well as CB1 and CB2, which are the cannabinoid receptors widely distributed throughout the body. ese cannabinoid receptors are activated by different ligands, either endogenous, such as EC, or exogenous, such as plant cannabinoids as well as synthetic compounds [18]. e ECS is associated with the regulation of several human physiological processes, such as sleep and the immune response
The combination of either AEA or OEA with poly-L-lysine notably reduced bacterial growth (Figures 2(a) and 2(b)). Both AEA alone and AEA mixed with poly-L-lysine at doses up to 12.5 μg/ml had no effect on bacterial growth (Figure 2(a))

Summary

Research Article

Mark Feldman ,1 Ronit Sionov, Reem Smoum, Raphael Mechoulam, Isaac Ginsburg, and Doron Steinberg 1. We investigated the combinatory effect of the selected EC/EC-like with a natural antimicrobial agent, poly-L-lysine, on cariogenic bacteria Streptococcus mutans growth and biofilm formation. Among four tested EC/EC-like, only two, anandamide (AEA) and oleoylethanolamide (OEA), exhibited synergistic combinatory effect with poly-L-lysine against S. mutans. We attribute this distinct effect to differences in the fatty acid chain structure of the selected EC/EC-like compounds. We demonstrated that the AEA and EC-like AraS compound effectively alter the pathogenicity of different MRSA strains [23]. We describe the combinatory effect of cationic poly-L-lysine and EC/EC-like on planktonic growth and biofilm formation of S. mutans

Materials and Methods

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Discussion