Potential combinations of endocannabinoid/endocannabinoid-like compounds and antibiotics against methicillin-resistant Staphylococcus aureus

PLoS One. 2020 Apr 15;15(4):e0231583. doi: 10.1371/journal.pone.0231583. eCollection 2020.

Abstract

Infections caused by antibiotic-resistant strains of Staphylococcus aureus have reached epidemic proportions globally. Our previous study showed antimicrobial effects of anandamide (AEA) and arachidonoyl serine (AraS) against methicillin (MET)-resistant S. aureus (MRSA) strains, proposing the therapeutic potential of these endocannabinoid/endocannabinoid-like (EC/EC-like) agents for the treatment of MRSA. Here, we investigated the potential synergism of combinations of AEA and AraS with different types of antibiotics against MRSA grown under planktonic growth or biofilm formation. The most effective combinations under planktonic conditions were mixtures of AEA and ampicillin (AMP), and of AraS and gentamicin (GEN). The combination with the highest synergy in the biofilm formation against all tested bacterial strains was AEA and MET. Moreover, the combination of AraS and MET synergistically caused default of biofilm formation. Slime production of MRSA was also dramatically impaired by AEA or AraS combined with MET. Our data suggest the novel potential activity of combinations of EC/EC-like agents and antibiotics in the prevention of MRSA biofilm formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ampicillin / pharmacology
  • Ampicillin / therapeutic use
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Arachidonic Acids / pharmacology*
  • Arachidonic Acids / therapeutic use
  • Biofilms / drug effects
  • Cannabinoid Receptor Agonists / pharmacology*
  • Cannabinoid Receptor Agonists / therapeutic use
  • Drug Evaluation, Preclinical
  • Drug Synergism
  • Drug Therapy, Combination / methods
  • Endocannabinoids / pharmacology*
  • Endocannabinoids / therapeutic use
  • Gentamicins / pharmacology
  • Gentamicins / therapeutic use
  • Humans
  • Methicillin Resistance / drug effects
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Microbial Sensitivity Tests
  • Polyunsaturated Alkamides / pharmacology*
  • Polyunsaturated Alkamides / therapeutic use
  • Serine / analogs & derivatives
  • Serine / pharmacology
  • Serine / therapeutic use
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology

Substances

  • Anti-Bacterial Agents
  • Arachidonic Acids
  • Cannabinoid Receptor Agonists
  • Endocannabinoids
  • Gentamicins
  • N-arachidonoyl L-serine
  • Polyunsaturated Alkamides
  • Serine
  • Ampicillin
  • anandamide

Grants and funding

MF, RS, RM, DS; Partially supported by the chief scientist office of the ministry of agriculture; https://www.moag.gov.il/en/Ministrys%20Units/Ministers_Bureau/Pages/default.aspx; funders did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.