anandamide and Staphylococcal-Infections

Antibiotic-resistant

Topics: Anti-Bacterial Agents; Arachidonic Acids; Biochemical Phenomena; Endocannabinoids; GTP Phosphohydrolases; Humans; Methicillin-Resistant Staphylococcus aureus; Polyunsaturated Alkamides; Staphylococcal Infections; Staphylococcus aureus

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.

Topics: Ampicillin; Anti-Bacterial Agents; Arachidonic Acids; Biofilms; Cannabinoid Receptor Agonists; Drug Evaluation, Preclinical; Drug Synergism; Drug Therapy, Combination; Endocannabinoids; Gentamicins; Humans; Methicillin Resistance; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Polyunsaturated Alkamides; Serine; Staphylococcal Infections

Infections caused by antibiotic-resistant strains of Staphylococcus aureus have reached epidemic proportions globally. Staphylococcal biofilms are associated with increased antimicrobial resistance and are generally less affected by host immune factors. Therefore, there is an urgent need for novel agents that not only aim at multidrug-resistant pathogens, but also ones that will act as anti biofilms. In the present study, we investigated the antimicrobial activity of the endocannabinoid (EC) anandamide (AEA) and the endocannabinoid-like (EC-like), arachidonoyl serine (AraS) against methicillin resistant S. aureus strains (MRSA). We observed a strong inhibition of biofilm formation of all tested MRSA strains as well as a notable reduction of metabolic activity of pre-formed MRSA biofilms by both agents. Moreover, staphylococcal biofilm-associated virulence determinants such as hydrophobicity, cell aggregation and spreading ability were altered by AEA and AraS. In addition, the agents were able to modify bacterial membrane potential. Importantly, both compounds prevent biofilm formation by altering the surface of the cell without killing the bacteria. Therefore, we propose that EC and EC-like compounds may act as a natural line of defence against MRSA or other antibiotic resistant bacteria. Due to their anti biofilm action these agents could also be a promising alternative to antibiotic therapeutics against biofilm-associated MRSA infections.

Topics: Anti-Bacterial Agents; Arachidonic Acids; Biofilms; Endocannabinoids; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Polyunsaturated Alkamides; Staphylococcal Infections

Toxic shock syndrome is a rare but potentially fatal toxin-mediated febrile illness. We report a case of toxic shock syndrome complicated by life-threatening organ dysfunction with high toxin-1 and staphylococcus enterotoxin type A levels that were successfully reduced by early introduction of plasma exchanges. The report shows the time course of the concentrations of anandamide and 2-arachidonyl glyceride and confirms that early introduction of plasma exchange can result in a rapid reduction of circulating toxins and mediators in the treatment of life-threatening multiple organ dysfunction.

Topics: Adolescent; Arachidonic Acids; Bacterial Toxins; Cannabinoid Receptor Modulators; Diglycerides; Endocannabinoids; Enterotoxins; Humans; Male; Plasma Exchange; Polyunsaturated Alkamides; Shock, Septic; Staphylococcal Infections; Staphylococcus aureus; Superantigens