Staphylococcus aureus stands as one of the most pervasive pathogens given its morbidity and mortality worldwide due to its roles as an infectious agent that causes a wide variety of diseases ranging from moderately severe skin infections to fatal pneumonia and sepsis. S. aureus produces a variety of exotoxins that serve as important virulence factors in S. aureus-related infectious diseases and food poisoning in both humans and animals. For example, staphylococcal enterotoxins (SEs) produced by S. aureus induce staphylococcal foodborne poisoning; toxic shock syndrome toxin-1 (TSST-1), as a typical superantigen, induces toxic shock syndrome; hemolysins induce cell damage in erythrocytes and leukocytes; and exfoliative toxin induces staphylococcal skin scalded syndrome. Recently, Panton–Valentine leucocidin, a cytotoxin produced by community-associated methicillin-resistant S. aureus (CA-MRSA), has been reported, and new types of SEs and staphylococcal enterotoxin-like toxins (SEls) were discovered and reported successively. This review addresses the progress of and novel insights into the molecular structure, biological activities, and pathogenicity of both the classic and the newly identified exotoxins produced by S. aureus.

Molecular characterization of isolates from staphylococcal food poisoning (SFP) outbreaks in Japan showed that the dominant lineage causing SFP outbreaks is clonal complex 81 (CC81), a single-locus variant of sequence type 1, coagulase type VII, positive for sea and/or seb , and positive for seh . Among various CC lineages producing staphylococcal enterotoxin A, CC81 showed the highest toxin productivity.

Staphylococcus aureus is an important bacterial pathogen causing bovine mastitis, but little is known about the virulence factor and the inflammatory responses in the mammary infection. Staphylococcal enterotoxin C (SEC) is the most frequent toxin produced by S. aureus, isolated from bovine mastitis. To investigate the pathogenic activity of SEC in the inflammation of the mammary gland and the immune responses in an animal model, mouse mammary glands were injected with SEC, and the clinical signs, inflammatory cell infiltration, and proinflammatory cytokine production in the mammary glands were assessed. SEC induced significant inflammatory reactions in the mammary gland, in a dose-dependent manner. SEC-injected mammary glands showed a severe inflammation with inflammatory cell infiltration and tissue damage. In addition, interleukin (IL)-1β and IL-6 production in the SEC-injected mammary glands were significantly higher than those in the PBS control glands. Furthermore, the SEC-induced inflammation and tissue damage in the mammary gland were specifically inhibited by anti-SEC antibody. These results indicated, for the first time, that SEC can directly cause inflammation, proinflammatory cytokine production, and tissue damage in mammary glands, suggesting that SEC might play an important role in the development of mastitis associated with S. aureus infection. This finding offers an opportunity to develop novel treatment strategies for reduction of mammary tissue damage in mastitis.

Streptococcus pneumoniae, a leading cause of invasive pneumococcal disease, is responsible for high mortality and morbidity worldwide. A previous study showed that the NLR family pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasomes are essential for caspase-1 activation and IL-1β production in the host response to S. pneumoniae infection. The function of NLRP3 in host innate immunity to S. pneumoniae was studied in vivo and in vitro. However, the role of AIM2 in host defence against S. pneumoniae remains unclear. Here, we show that AIM2-deficient (AIM2^–/–) mice display increased susceptibility to intra-nasal infection with S. pneumoniae in comparison to wild type mice and that this susceptibility was associated with defective IL-1β production. Macrophages from AIM2^–/– mice infected with S. pneumoniae showed impaired secretion of IL-1β as well as activation of the inflammasome, as determined by the oligomerisation of apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1 activation. Taken together, these results indicate that the AIM2 inflammasome is essential for caspase-1-dependent cytokine IL-1β production and eventual protection from pneumococcal infection in mice.