The virulence toolkit of Staphylococcus aureus: a comprehensive review of toxin diversity, molecular mechanisms, and clinical implications

Abstract

Purpose: This review examines the pathogenic mechanisms of Staphylococcus aureus, emphasizing its toxin-driven virulence factors, including pore-forming toxins, exfoliative toxins, and superantigens.

Methods: This paper was conducted using the available literature (PubMed/MEDLINE/Google Scholar and books written by experts in pharmacology and infectious diseases).

Results: Toxins are crucial in promoting tissue invasion, immune system evasion, and the development of systemic diseases. Notably, the qualitative and quantitative expression of these toxins influences the clinical presentation and severity of S. aureus infections. The paper explores toxins' role in S. aureus pathogenesis and clinical manifestations as well as current and emerging therapeutic strategies aimed at targeting these toxins, including antibiotics, monoclonal antibodies, and anti-inflammatory treatments. Additionally, it highlights the potential of novel inhibitors and vaccines to neutralize specific toxins and prevent toxin-mediated diseases.

Conclusion: By combining antimicrobial therapies with approaches that neutralize toxins and modulate the immune response, clinicians can improve outcomes in patients affected by S. aureus infections.

Keywords: Staphylococcus aureus; Anti-inflammatory treatments; Antibiotic therapy; Monoclonal antibodies; Toxins.

Fig. 1

General principles of pore-forming toxins (PFT) mechanism. Pore-forming toxins interact with cell membranes through specific binding to a membrane receptor or direct interaction with membrane components. Depending on the toxin class, the binding mechanism differs. Upon binding, the toxins oligomerize to form pores in the membrane, leading to dysregulated ion fluxes that ultimately results in cell death

Fig. 2

General principles of Exfoliative Toxins (ET) mechanism. ET specifically cleaves desmoglein-1, a critical component of cell junctions, leading to cell detachment and the exfoliation of epithelial tissue

Fig. 3

General principles of Superantigens mechanism. Superantigens can directly bind MHC class II molecules to T-cell receptors, triggering a constitutive and non-specific activation of T cells independent of specific antigens. This leads to a chain reaction resulting in the so-called cytokine storm and the massive activation of T cells, which ultimately undergo cell death

Fig. 4

Relationship between SCCmec element and toxin production in HA-MRSA vs. CA-MRSA

Fig. 5

Main cell type targets for the different toxins are shown