Type

Journal Article

Authors

Colin Hill
R Paul Ross
Paul D. Cotter
Paula M. O'Connor
Sheila M Morgan

Subjects

Microbiology

Topics
lactococcus lactis pharmacology peptides anti bacterial agents microbial sensitivity tests drug effects nisin bacteriocins chemistry lacticin 481 nanostructures

Sequential actions of the two component peptides of the lantibiotic lacticin 3147 explain its antimicrobial activity at nanomolar concentrations. (2005)

Abstract 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.
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Full list of authors on original publication

Colin Hill, R Paul Ross, Paul D. Cotter, Paula M. O'Connor, Sheila M Morgan

Experts in our system

1
Colin Hill
University College Cork
Total Publications: 351
 
2
R Paul Ross
Teagasc
Total Publications: 441
 
3
Paul D. Cotter
Teagasc
Total Publications: 253
 
4
Paula M. O'Connor
Teagasc
Total Publications: 85