Staphylococcal α Toxin

Abstract

Staphylococcal α toxin is a major pathogenicity determinant of Staphylococcus aureus (Bhakdi and Tranum-Jensen 1991). It is not produced by coagulase-negative staphylococci, and this is probably one reason for their reduced virulence compared with S. aureus. The toxin is secreted as a 293-residue water-soluble monomer of molecular weight 33000Da (Gray and Kehoe 1984). Gene expression is subject to complex regulation (Recsei et al. 1986). Antibodies against α toxin become detectable in sera of all young adults, indicating that toxin production occurs in humans even in the absence of clinical disease. Similarly, antibodies can be found in sera of domestic animals, reflecting the fact that S. aureus is a most versatile pathogen that infects a broad spectrum of hosts. S. aureus infections range from self-limiting skin afflictions to life-threatening systemic diseases, and S. aureus is a major causative agent of hospital infections. Inasmuch as the pathogenesis of staphylococcal disease is multifactorial, α toxin probably assumes a dominant role in most cases. In animal models, purified toxin has been shown to be hemolytic, dermonecrotic, and lethal (McCartney and Arbuthnott 1978). The biological importance of toxin production has formally been shown by two approaches. First, the use of genetically deficient bacterial-mutant strains has proven α toxin to be a major cause of tissue destruction and abscess formation (Jonsson et al. 1985; Patel et al. 1987; Bramley et al. 1989; Menzies and Kernodle 1994). Second, the application of mono-and polyclonal antibodies against α toxin has been found to protect against development of staphylococcal lesions. α Toxin is thus not only an archetype of a channel-forming bacterial toxin, it constitutes the best-studied example of how a pore-forming toxin can contribute to microbial virulence (Bhakdi and Tranum-Jensen 1991; Bhakdi et al. 1996).