Few of the cellular components of group A streptococci appear to be directly toxic for animals or humans. Some preparations of M
protein produce an immunotoxic effect on human platelets and neutrophils. Cell wall fragments produce a chronic multinodular inflammatory lesion of dermal connective tissue. The
peptidoglycan component of cell walls has many of the
biologic features of
endotoxins. The
exotoxins of group A streptococci include the erythrogenic toxins (pyrogenic
exotoxins) and the cytolytic toxins (
streptolysins S and O). The high prevalence of
erythrogenic, toxin-producing strains is difficult to reconcile with the epidemiologic behavior of
scarlet fever; the variations may be due to quantitative differences in toxin production or to a shift from the early
scarlet fever-associated strains that produce A toxin to the currently prevalent strains that produce B and C toxins. Experiments with animals suggest that a positive Dick test and the
rash of
scarlet fever result not from a direct toxic effect but rather from enhancement by pyrogenic
exotoxin(s) of acquired
hypersensitivity to diverse streptococcal products. The mechanism of toxigenic phage conversion is not clear. The pyrogenic
exotoxins are associated with the enhancement of
endotoxin shock and a wide variety of other
biologic properties.
Streptolysin S is a nonantigenic
polypeptide associated with various stabilizing carrier molecules. It lyses a wide range of mammalian cells, influences T lymphocyte functions, and is probably responsible for the leukotoxic property of group A streptococci.
Rheumatic fever has been associated with a streptococcal outbreak due to a nonhemolytic (
streptolysin S-negative) strain.
Streptolysin O is an
oxygen-labile (
thiol-activated)
cytolysin. It is inhibited by nonesterified
cholesterol and binds to
cholesterol in the membranes of mammalian cells and organelles, an interaction producing ring-like and C-shaped structures demonstrable by electron microscopy.
Streptolysin O affects a number of leukocyte functions. It produces profound electrocardiographic changes in experimental animals and toxic effects on pulsating heart cells in tissue culture. The observation that
rheumatic fever is not associated with
infection of the skin due to group A streptococci has suggested that nonesterified
cholesterol in the epidermis may inhibit a toxic effect of
streptolysin O, an effect necessary for the development of
rheumatic fever.