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Antimicrobial Agents and Chemotherapy, April 2009, p. 1610-1618, Vol. 53, No. 4
0066-4804/09/$08.00+0     doi:10.1128/AAC.01040-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Lipopeptide Antibiotic Friulimicin B Inhibits Cell Wall Biosynthesis through Complex Formation with Bactoprenol Phosphate{triangledown}

T. Schneider,1* K. Gries,1 M. Josten,1 I. Wiedemann,1 S. Pelzer,2,§ H. Labischinski,2 and H.-G. Sahl1

Institute of Medical Microbiology, Immunology and Parasitology, Pharmaceutical Microbiology Section, University of Bonn, Meckenheimer Allee 168, D-53115 Bonn, Germany,1 MerLion Pharmaceuticals GmbH, Robert-Roessle-Str. 10, D-13125 Berlin, Germany2

Received 4 August 2008/ Returned for modification 6 November 2008/ Accepted 10 December 2008

Friulimicin B is a naturally occurring cyclic lipopeptide, produced by the actinomycete Actinoplanes friuliensis, with excellent activity against gram-positive pathogens, including multidrug-resistant strains. It consists of a macrocyclic decapeptide core and a lipid tail, interlinked by an exocyclic amino acid. Friulimicin is water soluble and amphiphilic, with an overall negative charge. Amphiphilicity is enhanced in the presence of Ca2+, which is also indispensable for antimicrobial activity. Friulimicin shares these physicochemical properties with daptomycin, which is suggested to kill gram-positive bacteria through the formation of pores in the cytoplasmic membrane. In spite of the fact that friulimicin shares features of structure and potency with daptomycin, we found that friulimicin has a unique mode of action and severely affects the cell envelope of gram-positive bacteria, acting via a defined target. We found friulimicin to interrupt the cell wall precursor cycle through the formation of a Ca2+-dependent complex with the bactoprenol phosphate carrier C55-P, which is not targeted by any other antibiotic in use. Since C55-P also serves as a carrier in teichoic acid biosynthesis and capsule formation, it is likely that friulimicin blocks multiple pathways that are essential for a functional gram-positive cell envelope.

* Corresponding author. Mailing address: Institute of Pharmaceutical Microbiology, Meckenheimer Allee 168, D-53115 Bonn, Germany. Phone: 49 (0)228 73-5688. Fax: 49 (0)228 73-5267. E-mail: tanja{at}mibi03.meb.uni-bonn.de

{triangledown} Published ahead of print on 21 January 2009.

§ Present address: BRAIN (Biotechnology Research And Information Network) AG, Darmstädter Str. 34, D-64673 Zwingenberg, Germany.

Antimicrobial Agents and Chemotherapy, April 2009, p. 1610-1618, Vol. 53, No. 4
0066-4804/09/$08.00+0     doi:10.1128/AAC.01040-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Bottiger, T., Schneider, T., Martinez, B., Sahl, H.-G., Wiedemann, I. (2009). Influence of Ca2+ Ions on the Activity of Lantibiotics Containing a Mersacidin-Like Lipid II Binding Motif. Appl. Environ. Microbiol. 75: 4427-4434 [Abstract] [Full Text]  


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