Peptidomimetic Antibiotics Target Outer-Membrane Biogenesis in Pseudomonas aeruginosa

Author:

Srinivas Nityakalyani1,Jetter Peter1,Ueberbacher Bernhard J.1,Werneburg Martina1,Zerbe Katja1,Steinmann Jessica1,Van der Meijden Benjamin1,Bernardini Francesca2,Lederer Alexander2,Dias Ricardo L. A.2,Misson Pauline E.2,Henze Heiko2,Zumbrunn Jürg2,Gombert Frank O.2,Obrecht Daniel2,Hunziker Peter3,Schauer Stefan3,Ziegler Urs4,Käch Andres4,Eberl Leo5,Riedel Kathrin5,DeMarco Steven J.2,Robinson John A.1

Affiliation:

1. Chemistry Department, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.

2. Polyphor AG, Hegenheimermattweg 125, 4123 Allschwil, Switzerland.

3. Functional Genomics Center Zürich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.

4. Center for Microscopy and Image Analysis, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.

5. Department of Microbiology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich.

Abstract

Killing Pseudomonas Gram-negative Pseudomonas bacteria are opportunistic pathogens, and drug-resistant strains present a serious health problem. Srinivas et al. (p. 1010 ) synthesized a family of peptidomimetic antibiotics that is active only against Pseudomonas . These antibiotics do not lyse the cell membrane, but instead target an essential outer membrane protein, LptD, which plays a role in the assembly of lipopolysaccharide in the outer cell membrane. Activity in a mouse infection model suggests that the antibiotics might have therapeutic potential. In addition, LptD is widely distributed in gram-negative bacteria and so its validation as a target has the potential to drive development of antibiotics with a broader spectrum of activity against gram-negative pathogens.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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