α-Alkylidene δ-lactones inhibit quorum sensing phenotypes in Chromobacterium strain CV026 showing interaction with the CviR receptor

• Autor(a) principal: Favero, Fernanda
• Data de Publicação: 2023
• Outros Autores: Tolentino, Terezinha Alves, Fernandes, Vinicius, Treptow, Werner, Pereira, Alex Leite, Machado, Angelo Henrique Lira
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UnB
• Texto Completo: http://repositorio2.unb.br/jspui/handle/10482/46916; https://doi.org/10.1039/D3RA01975F; https://orcid.org/0000-0003-4284-9929
• topic: Bactérias; Lactonas

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.