On the basis of chemical and immunologic evidence, most investigators now
believe that Staphylococcus aureus may produce at least four distinct hemolytic
proteins. These have been designated alpha, beta, gamma and delta hemolysins.
The function of these hemolysins in the economy of the Staphylococcus has not
been fully elucidated, but some detail is available with regard to their nature
and in vitro mode of action. Agreement on the properties of the four hemolysins
has nevertheless been difficult to obtain because of wide variation in methods
of purification and choice of strains. Moreover, confusion has existed in
many laboratories with regard to the identity of the hemolysin under study.Recent work has permitted a number of generalizations to be made. Amino
acid analyses of the hemolysins have revealed that no unusual acids are present.
All hemolysins are soluble in water although of somewhat varying stability,
and when pure, no carbohydrate, lipid or other accessory materials have been
detected. It is also fairly well-established that at least three, the alpha,
beta and delta hemolysins, are basic proteins the isoelectric points of which
are in the range of 8.5-9.6. Apart from the delta lysin, their molecular
weights are less than 100,000 daltons, the majority of observations being in
the range of 20,000-50,000 daltons.The mode of action of the hemolysins has generated some debate, but it is
accepted that the beta lysin is an enzyme which degrades sphingomyelin, a phospho¬
lipid widely distributed in cell membranes. The view that the delta lysin is
also a phospholipase which attacks phosphatidyl-inositol has frequently been
challenged but it must be pointed out that until very recently, workers have
not clearly distinguished between gamma and delta lysins. The precise mode of
action of the latter is unknown but contemporary work indicates that although
gamma lysin has no action on sphingomyelin, phosphatidylinositol or other
comnon phospholipids, nitrogen and phosphorus are released from erythrocyte
membranes treated with the lysin. Furthermore, it can be shown that hemolysis
is inhibited by the membranes when these are added to lysin-red cell suspensions,
and that phospholipids extracted from human erythrocytes competitively inhibit
the lytic reaction. The mode of action of the alpha lysin has also been
elusive but considerable evidence has been compiled which indicates that the
lysin is produced by the Staphylococcus as an inactive protease which degrades
membranes that contain an activating protease. It has been observed that
hemolytic sensitivity of erythrocyte species to alpha lysin is directly
correlated with the level of activator present on the membranes. Apart from
this, several investigators have demonstrated that the lysin has surface
activity, but it is difficult to reconcile the two points of view.No agreement has been reached on the biological properties of the beta,
ganma and delta hemolysins in view of the difficulties of purification and
definition. Most workers agree, however, that the alpha lysin kills mice and
rabbits in doses at the microgram level (although it is thousands of times
less toxic than botulinum or tetanus toxins) and that it causes tissue necrosis
when injected into the skin. In vivo production of the hemolysins in animals
and man has been demonstrated by the detection of circulating antibody in
normal and diseased subjects, but until the present, controversy existed
over whether the delta lysin was in fact capable of eliciting an antibody
response, since serum lipoproteins inhibited its lytic activity. The use of
homogeneous preparations of the lysin and purified antibody has conclusively
demonstrated its immunogenicity
