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Antimicrobial Agents and Chemotherapy, April 2006, p. 1449-1457, Vol. 50, No. 4
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.4.1449-1457.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Insights into In Vivo Activities of Lantibiotics from Gallidermin and Epidermin Mode-of-Action Studies{dagger}

Raquel Regina Bonelli, Tanja Schneider, Hans-Georg Sahl, and Imke Wiedemann*

Institut für Medizinische Mikrobiologie, Immunologie und Parasitologie, Pharmazeutische Mikrobiologie, Universität Bonn, D-53115 Bonn, Germany

Received 30 September 2005/ Returned for modification 29 November 2005/ Accepted 6 January 2006

The activity of lanthionine-containing peptide antibiotics (lantibiotics) is based on different killing mechanisms which may be combined in one molecule. The prototype lantibiotic nisin inhibits peptidoglycan synthesis and forms pores through specific interaction with the cell wall precursor lipid II. Gallidermin and epidermin possess the same putative lipid II binding motif as nisin; however, both peptides are considerably shorter (22 amino acids, compared to 34 in nisin). We demonstrate that in model membranes, lipid II-mediated pore formation by gallidermin depends on membrane thickness. With intact cells, pore formation was less pronounced than for nisin and occurred only in some strains. In Lactococcus lactis subsp. cremoris HP, gallidermin was not able to release K+, and a mutant peptide, [A12L]gallidermin, in which the ability to form pores was disrupted, was as potent as wild-type gallidermin, indicating that pore formation does not contribute to killing. In contrast, nisin rapidly formed pores in the L. lactis strain; however, it was approximately 10-fold less effective in killing. The superior activity of gallidermin in a cell wall biosynthesis assay may help to explain this high potency. Generally, it appears that the multiple activities of lantibiotics combine differently for individual target strains.


* Corresponding author. Mailing address: Pharmazeutische Mikrobiologie, Universität Bonn, Meckenheimer Allee 168, D-53115 Bonn, Germany. Phone: 49 (228) 73 4637. Fax: 49 (228) 73 4637. E-mail: Imke.Wiedemann{at}ukb.uni-bonn.de.

{dagger} This paper is dedicated to Professor Hans-Georg Trüper on the occasion of his 70th birthday.


Antimicrobial Agents and Chemotherapy, April 2006, p. 1449-1457, Vol. 50, No. 4
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.4.1449-1457.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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