e-journal
The diversity of receptor recognition in cholesteroldependent cytolysins
Cholesterol-dependent cytolysins (CDCs) are bacterial pore-forming toxins secreted mainly by
pathogenic Gram-positive bacteria. CDCs generally recognize and bind to membrane cholesterol to
create pores and lyse target cells. However, in contrast to typical CDCs such as streptolysin O, several
atypical CDCs have been reported. The first of these was intermedilysin, which is secreted by
Streptococcus intermedius and has human cell-specificity, human CD59 (huCD59) being its receptor.
In the study reported here, the diversity of receptor recognition among CDCs was investigated and
multi-receptor recognition characteristics were identified within this toxin family. Streptococcus
mitis-derived human platelet aggregation factor (Sm-hPAF) secreted by S. mitis strain Nm-65 isolated
from a patient with Kawasaki disease was previously shown to hemolyze erythrocytes in a speciesdependent
manner, its maximum activity being in human cells. In the present study, it was found that
Sm-hPAF recognizes both membrane cholesterol and huCD59 as receptors for triggering poreformation.
Moreover, vaginolysin (VLY) of Gardnerella vaginalis showed similar characteristics to
Sm-hPAF regarding receptor recognition. On the basis of the results presented here, the mode of
receptor recognition of CDCs can be categorized into the following three groups: (i) Group I,
comprising typical CDCs with high affinity to cholesterol and no or very little affinity to huCD59; (ii)
Group II, including atypical CDCs such as ILY, with no or very little affinity to cholesterol and high
affinity to huCD59; and (iii) Group III, which contains atypical CDCs such as Sm-hPAF and VLY with
affinity to both cholesterol and huCD59.
Key words cholesterol-dependent cytolysins, receptor recognition, Streptococcus mitis-derived human platelet
aggregation factor, vaginolysin.
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