ArticleScientific reports2016
Discovery of new diketopiperazines inhibiting Burkholderia cenocepacia quorum sensing in vitro and in vivo.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 56 citations in OpenAlex.
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- Biocontrol of biofilm forming Burkholderia cepacia using a quorum quenching crude lactonase enzyme extract from a marine Chromohalobacter sp. strain D23.Archives of microbiology · 2023Article
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- Compilation of the Antimicrobial Compounds Produced byMolecules (Basel, Switzerland) · 2023Review
- Methodological tools to study species of the genus Burkholderia.Applied microbiology and biotechnology · 2021Review
- Current and Emerging Therapies to Combat Cystic Fibrosis Lung Infections.Microorganisms · 2021Review
- Design, synthesis, and evaluation of transition-state analogs as inhibitors of the bacterial quorum sensing autoinducer synthase CepI.Bioorganic & medicinal chemistry letters · 2021Article
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- Prospects of Indole derivatives as methyl transfer inhibitors: antimicrobial resistance managers.BMC pharmacology & toxicology · 2020Article
- Chemical, Metabolic, and Cellular Characterization of a FtsZ Inhibitor Effective AgainstFrontiers in microbiology · 2020Article
- Phenylacetyl Coenzyme A, Not Phenylacetic Acid, Attenuates CepIR-Regulated Virulence in Burkholderia cenocepacia.Applied and environmental microbiology · 2019Article
- Potent modulation of the CepR quorum sensing receptor and virulence in a Burkholderia cepacia complex member using non-native lactone ligands.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Burkholderia cenocepacia, an opportunistic respiratory pathogen particularly relevant for cystic fibrosis patients, is difficult to eradicate due to its high level of resistance to most clinically relevant antimicrobials. Consequently, the discovery of new antimicrobials as well as molecules capable of inhibiting its virulence is mandatory. In this regard quorum sensing (QS) represents a good target for anti-virulence therapies, as it has been linked to biofilm formation and is important for the production of several virulence factors, including proteases and siderophores. Here, we report the discovery of new diketopiperazine inhibitors of the B. cenocepacia acyl homoserine lactone synthase CepI, and report their anti-virulence properties. Out of ten different compounds assayed against recombinant CepI, four were effective inhibitors, with IC50 values in the micromolar range. The best compounds interfered with protease and siderophore production, as well as with biofilm formation, and showed good in vivo activity in a Caenorhabditis elegans infection model. These molecules were also tested in human cells and showed very low toxicity. Therefore, they could be considered for in vivo combined treatments with established or novel antimicrobials, to improve the current therapeutic strategies against B. cenocepacia.
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