Streptococcus anginosus is a commensal of the oral mucosa that can cause severe invasive infections. A considerable proportion of Streptococcus anginosus strains are ß‐hemolytic due to the presence of an SLS‐like gene cluster. However, the majority of strains do not display ß‐hemolysis. To investigate ß‐hemolysin heterogeneity in S. anginosus, we determined the presence of sag genes and correlated it with the presence of CRISPR/Cas genes in a collection of ß‐hemolytic and non‐ß‐hemolytic strains. All of the ß‐hemolytic strains carried the sag gene cluster. In contrast to other streptococci, clinical S. anginosus strains that do not display ß‐hemolysis do not harbor sag genes. Phylogenetic analysis of the ß‐hemolytic strains revealed that they belong to two previously defined clusters within S. anginosus. Correlation with CRISPR/Cas genes showed a significant difference for the presence of CRISPR/Cas in ß‐hemolytic versus non‐ß‐hemolytic isolates. The presence of the CRISPR/Cas type IIA or type IIC locus is associated with the absence of sag genes; in 65% of the non‐ß‐hemolytic strains a CRISPR/Cas locus was found, while only 24% of ß‐hemolytic strains carry CRISPR/Cas genes. Further analysis of the spacer content of the CRISPR systems revealed the presence of multiple self‐targeting sequences directed against S. anginosus genes. These results support the hypothesis that horizontal gene transfer is involved in the acquisition of ß‐hemolysin genes and that CRISPR/Cas may limit DNA uptake in S. anginosus.

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