Disruption of Quorum Sensing and Virulence in by a Structural Analogue of the -2-Dodecenoic Acid Signal.

Quorum sensing (QS) signals are widely used by bacterial pathogens to control biological functions and virulence in response to changes in cell population densities. employs a molecular mechanism in which the -2-dodecenoic acid (named iffusible ignal actor [BDSF]) QS system regulates -acyl homoserine lactone (AHL) signal production and virulence by modulating intracellular levels of cyclic diguanosine monophosphate (c-di-GMP). Thus, inhibition of BDSF signaling may offer a non-antibiotic-based therapeutic strategy against BDSF-regulated bacterial infections. In this study, we report the synthesis of small-molecule mimics of the BDSF signal and evaluate their ability to inhibit BDSF QS signaling in A novel structural analogue of BDSF, 14-Me-C (-14-methylpentadec-2-enoic acid), was observed to inhibit BDSF production and impair BDSF-regulated phenotypes in , including motility, biofilm formation, and virulence, while it did not inhibit the growth rate of this pathogen. 14-Me-C also reduced AHL signal production. Genetic and biochemical analyses showed that 14-Me-C inhibited the production of the BDSF and AHL signals by decreasing the expression of their synthase-encoding genes. Notably, 14-Me-C attenuated BDSF-regulated phenotypes in various species. These findings suggest that 14-Me-C could potentially be developed as a new therapeutic agent against pathogenic species by interfering with their QS signaling. is an important opportunistic pathogen which can cause life-threatening infections in susceptible individuals, particularly in cystic fibrosis and immunocompromised patients. It usually employs two types of quorum sensing (QS) systems, including the -2-dodecenoic acid (BDSF) system and -acyl homoserine lactone (AHL) system, to regulate virulence. In this study, we have designed and identified an unsaturated fatty acid compound (-14-methylpentadec-2-enoic acid [14-Me-C]) that is capable of interfering with QS signaling and virulence. We demonstrate that 14-Me-C reduced BDSF and AHL signal production in It also impaired QS-regulated phenotypes in various species. These results suggest that 14-Me-C could interfere with QS signaling in many species and might be developed as a new antibacterial agent.