Computer-aided design of agents that inhibit the cep quorum-sensing system of Burkholderia cenocepacia.

Abstract

Recent research has provided evidence that interference with bacterial cell-to-cell signaling is a promising strategy for the development of novel antimicrobial agents. Here we report on the computer-aided design of novel compounds that specifically inhibit an N-acyl-homoserine lactone-dependent communication system that is widespread among members of the genus Burkholderia. This genus comprises more than 30 species, many of which are important pathogens of animals and humans. Over the past few years, several Burkholderia species, most notably Burkholderia cenocepacia, have emerged as important opportunistic pathogens causing severe pulmonary deterioration in persons with cystic fibrosis. As efficient treatment of Burkholderia infections is hampered by the inherent resistance of the organisms to a large range of antibiotics, novel strategies for battling these pathogens need to be developed. Here we show that compounds targeting the B. cenocepacia signaling system efficiently inhibit the expression of virulence factors and attenuate the pathogenicity of the organism.

• Authors: Kathrin Riedel, Manuela Köthe, Bernd Kramer, Wael Saeb, Astrid Gotschlich, Aldo Ammendola, Leo Eberl
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 50 Issue 1 Pg. 318-23 (Jan 2006) ISSN: 0066-4804 [Print] United States
• PMID: 16377703 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Bacterial Proteins

Topics

• Anti-Bacterial Agents (pharmacology)
• Bacterial Proteins (antagonists & inhibitors)
• Burkholderia Infections (microbiology)
• Burkholderia cepacia (genetics, physiology)
• Computer-Aided Design
• Drug Design
• Gene Expression Regulation, Bacterial
• Signal Transduction (drug effects, physiology)