Staphylococcus aureus Toxins: From Their Pathogenic Roles to Anti-virulence Therapy Using Natural Products

Staphylococcus aureus (S. aureus) produces a wide variety of toxins that cause various diseases in humans. S. aureus toxins are divided into three categories; (i) superantigens (SAgs) that interfere with receptor function and cause toxic shock syndrome (TSS) or staphylococcal food poisoning (SFP), (ii) exfoliative toxins (ETs) that destroy epidermal barrier functions and cause staphylococcal scalded skin syndrome (SSSS), and (iii) cytotoxins that cause cell lysis. Recently, anti-toxin neutralizing agents have been engineered and proven to be effective in preventing or treating staphylococcal diseases. However, neutralization of a single toxin may not sufficiently protect the host from S. aureus infection. Biofilm formation and the pathogenesis of S. aureus are closely associated with accessory gene regulator-quorum sensing (agr-QS) system that controls the expressions of many virulence factors including exotoxins. In addition to anti-toxin antibodies, indirect approaches involving targeting of the agr-QS system are considered a novel means of inhibiting the virulence of S. aureus and controlling various diseases caused by the pathogen. This review summarizes basic concepts of the pathogenic roles of S. aureus toxins, the molecular features of the agr-QS system, and of natural product-based anti-virulence therapies that target virulence, rather than growth.