Sodium Salicylate Influences the Pseudomonas aeruginosa Biofilm Structure and Susceptibility Towards Silver

Abstract

Hard-to-heal wounds are typically infected with biofilm-producing microorganisms, such as Pseudomonas aeruginosa, which strongly contribute to delayed healing. Due to the global challenge of antimicrobial resistance, alternative treatment strategies are needed. Here, we investigated whether inhibition of quorum sensing (QS) by sodium salicylate in different P. aeruginosa strains (QS-competent, QS-mutant, and chronic wound strains) influences biofilm formation and tolerance to silver. Biofilm formation was evaluated in simulated serum-containing wound fluid in the presence or absence of sodium salicylate (NaSa). Biofilms were established using a 3D collagen-based biofilm model, collagen coated glass, and the Calgary biofilm device. Furthermore, the susceptibility of 48-h-old biofilms formed by laboratory and clinical strains in the presence or absence of NaSa towards silver was evaluated by assessing cell viability. Biofilms formed in the presence of NaSa were more susceptible to silver and contained reduced levels of virulence factors associated with biofilm development than those formed in the absence of NaSa. Biofilm aggregates formed by the wild-type but not the QS mutant strain, were smaller and less heterogenous in size when grown in cultures with NaSa compared to control. These data suggest that NaSa, via a reduction of cell aggregation in biofilms, allows the antiseptic to become more readily available to cells.

Role of sodium salicylate in Staphylococcus aureus quorum sensing, virulence, biofilm formation and antimicrobial susceptibility

“…The potential application for QS inhibitors lies not only in the modulation or inhibition of bacterial communication but also in their application alongside traditional treatment methods to potentiate their efficacy. The use of QS inhibitors to potentiate the effect of antimicrobial agents has been previously demonstrated, including sodium salicylate in combination with silver ( Gerner et al, 2021 ) and in combination with antibiotics ( Polonio Roy et al, 2001 ; Brackman et al, 2011 ; Belfield et al, 2017 ), showing increased MBEC susceptibility of S. epidermidis to vancomycin ( Polonio Roy et al, 2001 ). In this study, exposure to 10 mM NaSa resulted in a twofold decrease in the MBEC of rifampicin (from 1,024 to 512 μg/mL).…”

“…The effect of NaSa on biofilm susceptibility using silver was performed as described previously ( Gerner et al, 2021 ), but S. aureus ATCC 25923 was used to establish a biofilm for 24 h without inclusion of serum. Briefly, semisolid collagen type I gels with 0, 0.1, 1 or 10 mM NaSa were inoculated with 5 μL 10 8 CFU/mL bacteria.…”

“…There is a need to further ascertain if the benefits of QS modulation in decreasing toxic factors in S. aureus can outweigh the potential effects in persistence of infection, especially using clinically relevant in vitro biofilm models. Our group has previously investigated the effect of sodium salicylate (NaSa), which is the sodium salt of salicylic acid and is several hundred-fold more soluble in water than salicylic acid, showing decreased virulence ( Gerner et al, 2020 ) and increased susceptibility to silver in the Gram-negative pathogen P. aeruginosa ( Gerner et al, 2021 ).…”

Targeting Pseudomonas aeruginosa quorum sensing with sodium salicylate modulates immune responses in vitro and in vivo

“…This is, at least partly, related to the lack of appropriate understanding of the biological mechanisms governing the regulation of the immune response to the targeted microorganisms that have been exposed to QS-inhibiting substances. Our research group has previously shown that sodium salicylate (NaSa), the sodium salt of the bioactive metabolite of acetylsalicylic acid (Aspirin®), interferes with P. aeruginosa QS, reducing virulence factor and biofilm production ( Gerner et al., 2020 ; Gerner et al., 2021 ). In this study, we aim to evaluate the effect of NaSa on the ability of P. aeruginosa to modulate immune response processes, such as phagocytosis, immune cell migration, and secretion of cytokines, chemokines, and tissue-degrading enzymes.…”