Anti-quorum sensing and anti-biofilm activity of 5-hydroxymethylfurfural against Pseudomonas aeruginosa PAO1: Insights from in vitro, in vivo and in silico studies.

Pseudomonas aeruginosa is one of the most common pathogens associated with nosocomial infections and a great concern to immunocompromised individuals especially in the cases of cystic fibrosis, AIDS and burn wounds. The pathogenicity of P. aeruginosa is largely directed by the quorum sensing (QS) system. Hence, QS may be considered an important therapeutic target to combat P. aeruginosa infections. The anti-quorum sensing and anti-biofilm efficacy of aromatic aldehyde, 5-hydroxymethylfurfural (5-HMF) against P. aeruginosa PAO1 were assessed. At the sub-inhibitory concentration, 5-HMF suppressed the production of QS-controlled virulence phenotypes and biofilm formation in P. aeruginosa. It was also able to significantly enhance the survival rate of C. elegans infected with P. aeruginosa. The in silico studies revealed that 5-HMF could serve as a competitive inhibitor for the auto-inducer molecules as it exhibited a strong affinity for the regulatory proteins of the QS-circuits i.e. LasR and RhlR. In addition, a significant down-regulation in the expression of QS-related genes was observed suggesting the ability of 5-HMF in mitigating the pathogenicity of P. aeruginosa.