The production of streptocins STH 1 and STH 2 by Streptococcus gordonii DL1 (Challis) is directly controlled by the competence regulon, which requires intact comR and comAB loci. The streptocin (sth) locus comprises two functional genes, sthA and sthB. Whereas STH 1 activity requires sthA alone, STH 2 activity depends on both genes.In the 1970s, reported the production of streptocin STH 1 , a proteinaceous antimicrobial agent (bacteriocin), by the naturally transformable Streptococcus gordonii (formerly Streptococcus sanguis) strain Challis (also known as DL1 and NCTC 7868). Streptocin STH 1 biosynthesis coincided with the development of competence for genetic transformation (20, 21), a relationship supported by later studies (8,23). The inhibitory spectrum of streptocin STH 1 was initially reported to include other S. gordonii strains (e.g., strains Wicky and C219) and select strains of Streptococcus mitis and Streptococcus oralis (8,23). However, we have observed that the bacteriocin activity targeting S. mitis and S. oralis appears to be linked to the beta-hemolytic phenotype of strain Challis because S. gordonii OB164 (originally designated DL1-Challis), a non-beta-hemolytic strain indistinguishable from DL1 biochemically (API 20 Strep; bioMérieux, France) and genotypically (18), exhibited inhibitory activity only against S. gordonii isolates. This suggested that strain DL1 produces two bacteriocins: the previously described STH 1 (20) and the newly designated STH 2 , a bacteriocin that targets certain non-S. gordonii strains and is associated with the beta-hemolytic phenotype. Based on our speculation that genetic competence and bacteriocin production may be functionally related in strain DL1 (23), the aims of the present study were to determine whether bacteriocin biosynthesis is genetically associated with competence development and to define the locus encoding the inhibitory/hemolytic agents.(Parts of this work were presented at the 7th ASM Conference on Streptococcal Genetics, Saint Malo, France [7a].)Association of competence and bacteriocin/-hemolysin production. Competence development in S. gordonii is analogous to competence development in Streptococcus pneumoniae, occurring in two distinct stages, early and late (10, 13). The early stage involves a quorum-sensing signal transduction circuit comprising a secreted competence-stimulating peptide (CSP), its cell surface receptor ComD (a histidine kinase), and ComE, the primary transcriptional regulator of competence (10, 13). ComE, when activated by ComD, upregulates the comCDE (signal transduction), comAB (CSP secretion), and comX operons (13). ComX, an alternative sigma factor, connects the early and late stages by activating expression of the late competence operons that are responsible for DNA uptake and processing (17). Several key components of the S. gordonii competence regulon have been identified, including comCDE, comAB, comYA (DNA uptake), and duplicate comR (comX homologue) loci (6,7,15,16).In this study, early (comC, comE, comA, comB, an...
