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Antimicrobial Agents and Chemotherapy, July 2005, p. 2606-2611, Vol. 49, No. 7
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.7.2606-2611.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Sequential Actions of the Two Component Peptides of the Lantibiotic Lacticin 3147 Explain Its Antimicrobial Activity at Nanomolar Concentrations

Sheila M. Morgan,1,2 Paula M. O'Connor,1,2 Paul D. Cotter,3 R. Paul Ross,1,2* and Colin Hill2,3

Teagasc, Dairy Products Research Centre, Moorepark, Fermoy, Co. Cork, Ireland,1 Microbiology Department, University College, Cork, Co. Cork, Ireland,3 Alimentary Pharmabiotic Centre, Cork, Ireland2

Received 25 August 2004/ Returned for modification 24 November 2004/ Accepted 28 February 2005

Lacticin 3147 is a two-peptide (LtnA1 and LtnA2) lantibiotic produced by Lactococcus lactis subsp. lactis DPC3147 and has inhibitory activity against all gram-positive microorganisms tested. In this study the specific activities of the component peptides (alone or in combination) were determined by using L. lactis subsp. cremoris HP as the target strain. Lacticin 3147 exhibited an MIC50 of 7 nM for each component peptide (in combination), suggesting a peptide stoichiometry of 1:1. Interestingly, the LtnA1 peptide demonstrated independent inhibitory activity, with an MIC50 of 200 nM against L. lactis HP. In parallel studies, the single peptide bacteriocin nisin exhibited an MIC50 of 50 nM against the same target strain. Sequential peptide addition (with an intermediate washing step) demonstrated that LtnA1 must be added before LtnA2 rather than vice versa to observe inhibitory activity. The nanomolar activity of the lacticin peptides suggests the involvement of a docking molecule, speculated to be lipid II. Taken together with the recently determined structure of lacticin 3147 (N. I. Martin, T. Sprules, M. R. Carpenter, P. D. Cotter, C. Hill, R. P. Ross, and J. C. Vederas, Biochemistry, 43:3049-3056, 2004), these data support the hypothesis that the mode of action for lacticin 3147 involves a lipid II binding step (by the mersacidin-like LtnA1 peptide, which would explain its independent inhibitory activity), followed by insertion of the more linear LtnA2 peptide into the target membrane, resulting in pore formation and ultimate cell death.

* Corresponding author. Mailing address: Teagasc, Dairy Products Research Centre, Moorepark, Fermoy, Co. Cork, Ireland. Phone: 353 25 42229. Fax: 353 25 42340. E-mail: pross{at}moorepark.teagasc.ie.

Antimicrobial Agents and Chemotherapy, July 2005, p. 2606-2611, Vol. 49, No. 7
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.7.2606-2611.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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