Lantibiotic streptin

Streptolysin S (SLS) is a serum-extractable and oxygen-stable hemolysin produced by Group A Streptococcus. A SLS-deficient mutant in which transposon Tn 916 was inserted in a locus distinct from the sag gene cluster [Nizet et al. (2000) Infect. Immun. 68, 4245-4254] was obtained by filter mating of the transposon-harbouring Enterococcus faecalis strain and Streptococcus pyogenes BL(T). This mutant, N22, had completely lost the hemolytic activity, in consequence of insertion of a single Tn 916 into a hitherto-unknown lantibiotic gene cluster composed of 10 open reading frames. The arrangement and sequence of this lantibiotic gene cluster were similar to those of nisin and subtilin, and so we designated this new lantibiotic as streptin. The bactericidal activity of streptin was abolished on treatment with trypsin or proteinase K. The different host range and nucleotide sequence clearly distinguished streptin from streptococcins. Streptin was not hemolytic and its bacteriocin activity was independent of carrier oligonucleotides effective for SLS. The fact that N22 also lost the anti-bacterial activity against indicator streptococci reveals that the factor(s) required for lantibiotic formation plays an important role in SLS formation as well.

Beta-hemolytic streptococci cause a variety of infectious diseases associated with high morbidity and mortality. A key factor for successful infection is host colonization, which can be difficult in a multispecies environment. Secreting bacteriocins can be beneficial during this process. Bacteriocins are small, ribosomally produced, antimicrobial peptides produced by bacteria to inhibit the growth of other, typically closely related, bacteria. In this systematic review, bacteriocin production and regulation of beta-hemolytic streptococci was surveyed. While Streptococcus pyogenes produces eight different bacteriocins (Streptococcin A-FF22/A-M49, Streptin, Salivaricin A, SpbMN, Blp1, Blp2, Streptococcin A-M57), only one bacteriocin of Streptococcus agalactiae (Agalacticin = Nisin P) and one of Streptococcus dysgalactiae subsp. equisimilis (Dysgalacticin) has been described. Expression of class I bacteriocins is regulated by a two-component system, typically with autoinduction by the bacteriocin itself. In contrast, a separate quorum sensing system regulates expression of class II bacteriocins. Both identified class III bacteriocins are plasmid-encoded and regulation has not been elucidated.

Approximately 10% of Streptococcus pyogenes strains inhibit the growth of all nine indicators in a standardized streptococcal bacteriocin typing scheme. The present study has shown that this inhibitory profile, referred to as bacteriocin producer (P)-type 777 activity, is due to the type A1 lantibiotic streptin. Two major forms of streptin were purified to homogeneity from 95% acidified (pH 2) methanol extracts of S. pyogenes M25 cells by using a series of reversed-phase chromatographic separations. The fully processed form of streptin (streptin 1) is a 23-amino-acid peptide with a mass of 2,424 Da. The 2,821-M(r) form of the peptide (streptin 2) has three additional amino acids (TPY) at the N terminus. Strain M25 extracts also contained small quantities of the streptin 1 and streptin 2 peptides in various stages of dehydration. Streptin 1 and streptin 2 were each capable of specifically inducing streptin production when added to strain M25 cultures. The streptin gene cluster resembled that of other type A1 lantibiotics but appeared to lack a streptin-specific proteinase gene. Although the streptin structural gene (srtA) was widespread within S. pyogenes, being detected in 40 of 58 strains, each representing a different M serotype, only 10 of these srtA-positive strains produced active streptin. The failure of some strains to express streptin was attributed to an approximately 4.5-kb deletion in their streptin loci, encompassing genes putatively encoding proteins involved in streptin processing (srtB and srtC) and transport (srtT). In other strains, srtA transcription appeared to be defective. No direct association could be detected between the production of streptin and the production of the lantibiotic-like hemolysin streptolysin S in strain M25.