2026-10-14T15:03:28Z https://www.scidb.cn/oai

10.57760/sciencedb.37367 2026-05-25T18:06:34Z

2026-05-25 Targeting the Fsr quorum sensing system in Enterococcus faecalis: A salt bridge-driven anti-virulence strategy by γ-linolenic acid doi:10.57760/sciencedb.37367 en Objectives: The Fsr quorum sensing (QS) system of Enterococcus faecalis governs virulence factor expression and biofilm formation, positioning FsrB as an attractive anti-virulence target. This study elucidated the molecular mechanism by which γ-linolenic acid (GLA) disrupts Fsr QS signaling and suppresses pathogenicity.Methods: Gene expression profiling of the Fsr regulon was performed in clinical E. faecalis isolates treated with GLA and structurally analogous essential fatty acids. Ligand binding modes to the FsrB protein were resolved through molecular docking and protein-ligand interaction profiling. A CRISPR-Cas9 engineered K77I substitution in the OG1RF background provided definitive genetic validation of the key interaction interface.Results: Among the fatty acids tested, GLA alone consistently downregulated gelE and sprE gene transcript levels. Interaction profiling revealed a short distance salt bridge (2.49 Å) between the GLA carboxylate moiety and LYS77 of FsrB, a critical ionic contact absent or geometrically suboptimal in non-inhibitory analogs. The K77I isogenic mutant exhibited complete loss of GLA mediated virulence gene suppression, establishing a causal relationship between LYS77 engagement and FsrB inhibition.Conclusions: GLA inhibits the E. faecalis Fsr QS system via a LYS77 directed salt bridge that locks FsrB in a catalytically incompetent conformation. This mechanistic blueprint establishes a structural rationale for the development of salt bridge targeted anti-virulence agents against persistent enterococcal infections. γ-linolenic acid; Enterococcus faecalis; Fsr quorum sensing system; salt bridge; anti-virulence strategy; CRISPR-Cas9 Ming Wei Peng Wang Tianmeng Li Jun Liu Li Gu Shuai Wang PUBLIC https://creativecommons.org/licenses/by/4.0/ dataset Science Data Bank