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Journal of Bacteriology, July 2001, p. 3931-3938, Vol. 183, No. 13
0021-9193/01/$04.00+0   DOI: 10.1128/JB.183.13.3931-3938.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Intra- and Interspecies Signaling between Streptococcus salivarius and Streptococcus pyogenes Mediated by SalA and SalA1 Lantibiotic Peptides

M. Upton,1,2,dagger J. R. Tagg,2 P. Wescombe,2 and H. F. Jenkinson1,*

Department of Oral and Dental Science, University of Bristol Dental School, Bristol, BS1 2LY, United Kingdom,1 and Department of Microbiology, University of Otago, Dunedin, New Zealand2

Received 28 November 2000/Accepted 10 April 2001

Streptococcus salivarius 20P3 produces a 22-amino-acid residue lantibiotic, designated salivaricin A (SalA), that inhibits the growth of a range of streptococci, including all strains of Streptococcus pyogenes. Lantibiotic production is associated with the sal genetic locus comprising salA, the lantibiotic structural gene; salBCTX genes encoding peptide modification and export machinery proteins; and salYKR genes encoding a putative immunity protein and two-component sensor-regulator system. Insertional inactivation of salB in S. salivarius 20P3 resulted in abrogation of SalA peptide production, of immunity to SalA, and of salA transcription. Addition of exogenous SalA peptide to salB mutant cultures induced dose-dependent expression of salA mRNA (0.2 kb), demonstrating that SalA production was normally autoregulated. Inactivation of salR encoding the response regulator of the SalKR two-component system led to reduced production of, and immunity to, SalA. The sal genetic locus was also present in S. pyogenes SF370 (M type 1), but because of a deletion across the salBCT genes, the corresponding lantibiotic peptide, designated SalA1, was not produced. However, in S. pyogenes T11 (M type 4) the sal locus gene complement was apparently complete, and active SalA1 peptide was synthesized. Exogenously added SalA1 peptide from S. pyogenes T11 induced salA1 transcription in S. pyogenes SF370 and in an isogenic S. pyogenes T11 salB mutant and salA transcription in S. salivarius 20P3 salB. Thus, SalA and SalA1 are examples of streptococcal lantibiotics whose production is autoregulated. These peptides act as intra- and interspecies signaling molecules, modulating lantibiotic production and possibly influencing streptococcal population ecology in the oral cavity.

* Corresponding author. Mailing address: Department of Oral and Dental Science, University of Bristol Dental School, Lower Maudlin Street, Bristol, BS1 2LY, United Kingdom. Phone: 44 117 928 4358. Fax: 44 117 928 4313. E-mail: howard.jenkinson{at}bristol.ac.uk.

dagger Present address: Department of Medical Microbiology, Manchester Royal Infirmary, Manchester M13 9WL, United Kingdom.

Journal of Bacteriology, July 2001, p. 3931-3938, Vol. 183, No. 13
0021-9193/01/$04.00+0   DOI: 10.1128/JB.183.13.3931-3938.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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