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Science 15 September 2006:
Vol. 313. no. 5793, pp. 1636 - 1637
DOI: 10.1126/science.1129818

Reports

An Alternative Bactericidal Mechanism of Action for Lantibiotic Peptides That Target Lipid II

Hester E. Hasper,1 Naomi E. Kramer,1,2 James L. Smith,3 J. D. Hillman,4 Cherian Zachariah,5 Oscar P. Kuipers,2 Ben de Kruijff,1 Eefjan Breukink1*

Lantibiotics are polycyclic peptides containing unusual amino acids, which have binding specificity for bacterial cells, targeting the bacterial cell wall component lipid II to form pores and thereby lyse the cells. Yet several members of these lipid II–targeted lantibiotics are too short to be able to span the lipid bilayer and cannot form pores, but somehow they maintain their antibacterial efficacy. We describe an alternative mechanism by which members of the lantibiotic family kill Gram-positive bacteria by removing lipid II from the cell division site (or septum) and thus block cell wall synthesis.

1 Department of Biochemistry of Membranes, Bijvoet Center for Biomolecular Research, Institute of Biomembranes, Utrecht University, Padualaan 8, 3584 CH, Utrecht, Netherlands.
2 Department of Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Post Office Box 14, 9750 AA, Haren, Netherlands.
3 Department of Biological Sciences, Post Office Box GY, Mississippi State University, Mississippi State, MS 39762, USA.
4 Oragenics Incorporated, 13700 Progress Boulevard, Alachua, FL 32615, USA.
5 Banyon Biomarkers, 12085 Research Drive, Alachua, FL 32615, USA.

* To whom correspondence should be addressed. E-mail: e.j.breukink{at}chem.uu.nl

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