Título:	α-Alkylidene δ-lactones inhibit quorum sensing phenotypes in Chromobacterium strain CV026 showing interaction with the CviR receptor
Autor(es):	Favero, Fernanda Tolentino, Terezinha Alves Fernandes, Vinicius Treptow, Werner Pereira, Alex Leite Machado, Angelo Henrique Lira
ORCID:	https://orcid.org/0000-0003-4284-9929
Assunto:	Bactérias Lactonas
Data de publicação:	15-Jun-2023
Editora:	The Royal Society of Chemistry
Referência:	FAVERO, Fernanda et al. α-Alkylidene δ-lactones inhibit quorum sensing phenotypes in Chromobacterium strain CV026 showing interaction with the CviR receptor. RSC Advances, [S. l.], v. 13, p. 18045-18057, 2023. DOI: https://doi.org/10.1039/D3RA01975F. Disponível em: https://pubs.rsc.org/en/content/articlelanding/2023/ra/d3ra01975f. Acesso em: 27 nov. 2023.
Abstract:	Disruption of bacterial quorum sensing (QS) is presented as a promising strategy to overcome clinically relevant and phytopathogenic bacteria. This work presents α-alkylidene δ-lactones as new chemical scaffolds that inhibit the biosynthesis of violacein in the biosensor strain Chromobacterium CV026. Three molecules displayed higher than 50% violacein reduction when tested at concentrations lower than 625 µM. The most active α-alkylidene δ-lactone inhibited the hydrolysis of chitin concomitantly with the inhibition of violacein production in CV026, suggesting the disruption of its QS machinery. Further, RT-qPCR and competition experiments showed this molecule to be a transcriptional inhibitor of the QS-regulated operon vioABCDE. Docking calculations suggested a good correlation between binding affinity energies and inhibition effects, with all molecules positioned within the CviR autoinducer-binding domain (AIBD). The most active lactone yielded the best binding affinity energy, most probably due to its unprecedented binding with the AIBD. Our results show α-alkylidene δ-lactones as promising chemical scaffolds for the development of new QS inhibitors affecting LuxR/LuxI-systems.
Unidade Acadêmica:	Instituto de Química (IQ) Faculdade UnB Ceilândia (FCE) Instituto de Ciências Biológicas (IB) Departamento de Biologia Celular (IB CEL)
Licença:	(CC BY NC) This article is licensed under aCreative Commons Attribution-NonCommercial 3.0 Unported Licence.
DOI:	https://doi.org/10.1039/D3RA01975F
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