Dual functions of discoidinolysin, a cholesterol-dependent cytolysin with N-terminal discoidin domain produced from Streptococcus mitis strain Nm-76

Abstract

Background Some strains of Streptococcus mitis exhibit β-hemolysis due to the β-hemolytic activity of cholesterol-dependent cytolysin (CDC). Recently, a gene encoding an atypical lectinolysin-related CDC was found in S. mitis strain Nm-76. However, the product of this gene remains uncharacterized. We aimed to characterize this atypical CDC and its molecular functions and contribution to the pathogenicity of S. mitis strain Nm-76. Methods Phylogenetic analysis of the CDC gene was conducted based on the web-deposited information. The molecular characteristics of CDC were investigated using a gene-deletion mutant strain and recombinant proteins expressed in Escherichia coli . Results The gene encoding CDC found in Nm-76 and its homolog are distributed among many S. mitis strains. This CDC is phylogenetically different from other previously characterized CDCs, such as S. mitis -derived human platelet aggregation factor (Sm-hPAF)/lectinolysin and mitilysin. Because this CDC possesses an additional N-terminal domain, including a discoidin motif, it was termed discoidinolysin (DLY). In addition to the preferential lysis of human cells, DLY displayed N-terminal domain-dependent facilitation of human erythrocyte aggregation and intercellular associations between human cells. Conclusion DLY functions as a hemolysin/cytolysin and erythrocyte aggregation/intercellular association molecule. This dual-function DLY could be an additional virulence factor in S. mitis .

Characterization of tigurilysin, a novel human CD59-specific cholesterol-dependent cytolysin, reveals a role for host specificity in augmenting toxin activity

“…Once a CDC is anchored to the host cell surface, >30 units oligomerize to form a beta-barrel pore [19][20][21]. To date, four hCD59-dependent CDCs have been characterized: intermedilysin (ILY) produced by Streptococcus intermedius, lectinolysin (LLY) produced by Streptococcus mitis, vaginolysin (VLY) produced by Gardnerella vaginalis and, most recently, discoidinolysin (DLY) produced by S. mitis [17,[22][23][24]. Since there are few established hCD59-dependent CDCs, it is difficult to form a comprehensive overview of the evolution of hCD59-dependence and how that contributes to virulence for the bacteria producing such CDCs.…”

Characterization of Tigurilysin, a Novel Human CD59-Specific Cholesterol-Dependent Cytolysin, Reveals a Role for Host Specificity in Augmenting Toxin Activity

“…Once a CDC is anchored to the host cell surface, >30 units oligomerize to form a beta-barrel pore (19)(20)(21). To date, four hCD59-dependent CDCs have been characterized: intermedilysin (ILY) produced by Streptococcus intermedius, lectinolysin (LLY) produced by Streptococcus mitis, vaginolysin (VLY) produced by Gardnerella vaginalis, and most recently, discoidinolysin (DLY) produced by Streptococcus mitis (17,(22)(23)(24). Since there are few established hCD59-dependent CDCs, it is difficult to form a comprehensive overview of the evolution of hCD59-dependency and how that contributes to virulence for the bacteria producing such CDCs.…”