The association of dextran sodium sulfate to the bioactive agent I-modulia® attenuates Staphylococcus aureus virulence expression and δ-toxin production

As a part of the human skin commensal bacterial community, Staphylococcus aureus contributes to the host's immune system education. Nevertheless, it is also considered as an opportunistic pathogen involved in cutaneous infections or skin pathologies, in particular atopic dermatitis. To switch to a pathogenic behavior, S. aureus uses regulatory mechanisms to collectively produce virulence factors. Deprivation of these factors has emerged as a promising way to prevent or treat Staphylococcal diseases in facilitating the role of the immune system, while preserving the protective one of the commensal communities. This study focuses on the anti-virulent effect of dextran sodium sulfate (DSS) and I-modulia®, two natural products that have already proven their value in skincare. The anti-virulent capacity of DSS was first demonstrated by a dose-dependent inhibition of δ-toxin release, a virulence factor known to be a potent inducer of mast cell degranulation, on in vitro S. aureus cultures at high and low virulent states. A transcriptomic study was then implemented for a comprehensive overview of the anti-virulent impact. The results have shown the downregulation of many transcripts related to host immune evasion (scn, sbi), as well as exotoxins (α,γ-toxin) and adhesins production (map, emp), mostly under the control of SaeRS Two-Component System (TCS), one of the two major virulence regulators in S. aureus. Interestingly, genes related to secretion systems and the synthesis of exo-proteases were significantly downregulated when DSS was used in combination with I-modulia®. The repression of these genes was not previously observed and reflects a broader inhibitory action. We have also demonstrated that the inhibition of virulence factors didn't affect S. aureus viability. Our findings suggest that combining DSS and I-modulia® could be a promising therapeutic strategy to counteract microbial dysbiosis in the treatment of S. aureus skin pathologies in re-empowering the host's natural immune defenses.