Antibiofilm and antivirulence effect of stilbenes on clinically relevant staphylococci

Genus Staphylococcus comprises many greatly pathogenic species like S. aureus, S. epidermidis or S. saprophyticus. The great pathogenicity of stated species is often facilitated by their capability to form thick complex biofilms on various biotic or abiotic surfaces. Biofilm formation together with extracellular hydrolases or toxins represents important virulence factor, which increases persistence of staphylococci in host via enhancing their ability to evade host immune system and further promote the infection development. With an increased emergence of antibiotic resistance among pathogenic bacteria including staphylococci the search for novel antibiotic compounds with antivirulence effect is sought. Such substances might be stilbenes, phenolic compounds isolated from various plants (Vitis spp., Vaccinium spp., Pterocarpus spp., Pinus spp.). They possess strong antioxidant activity and a wide spectrum of beneficial pharmacological effects (antitumor, hypolipidemic, hypoglycemic). Apart from that, they also have great antimicrobial activity with a potent ability to enhance antibiotics action in combination.

Presented work focused on resveratrol, pterostilbene (PTE) and pinosylvine and their effect on S. aureus and S. epidermidis biofilm formation. The effect of stilbene representatives on production of other virulence factors (proteases, phospholipases, haemolysins), cell surface hydrophobicity and morphology was also observed.

PTE was found to be the most effective among studied stilbenes against S. aureus and S. epidermidis biofilm with minimum biofilm inhibitory concentrations (MBIC₈₀) ranging from 40 to 130 mg/l. Its effect on mature staphylococcal biofilm eradication was even greater with 80% eradication rate achieved by 40-75 mg/l. PTE (49 mg/l) was found to have a potent combinatory antibiofilm activity with erythromycin or tetracycline (5 mg/l both) causing more than 80% inhibition in metabolic activity of biofilm cells. It was able to permeabilize cytoplasmic membrane, thus probably enabling antibiotic uptake by the cell. PTE also altered cell surface hydrophobicity and production of haemolysin.

PTE might be the solution to increasing biofilm-related resistance problem and a promising candidate with antibiofilm and antivirulence potential for future antibiotic treatment of staphylococcal infections.

 

This work was supported by the grant of Specific university research – grant No. A2_FPBT_2020_004.