Proteomic-driven elucidation of molecular mechanisms of natural bioactives against biofilm mediated virulence in bacterial and fungal pathogens

Quorum Sensing (QS) is an intercellular communication conduit with respect to population in both bacteria and fungi. Microbes utilizes QS molecules for establishing pathogenicity in host through regulation of its key virulence factors such as cell aggregation (biofilm), production of hydrolytic enzymes and pigments. The aggregation ability of biofilm cells develops their capacity to evade the host defence and to resist conventional antibiotics. The antibiotic resistance progresses owing to the physiological adaptations such as slow growth. Therefore antibiotics inhibiting growth mediated virulence may increase the probability of a pathogen to develop resistance against antibiotics. Many research studies reported that natural compounds possess therapeutic efficacy to reduce pathogenicity without exerting cell toxicity. Proteomic study accomplished by our research group has revealed that curcumin from Curcuma longa reduced Pseudomonas aeruginosa PAO1 biofilm and virulence by regulating the pigments such as pyoverdine and pyocyanin, antioxidant enzymes and iron acquisition mechanisms. Also, vanillic acid from Actinidia deliciosa was found to impede proteins involved in surface layer, histidine, flagellin and fatty acid biosynthesis in Serratia marcescens thereby reducing key virulence factors such as biofilm, protease, prodigiosin, lipase and swarming motility. In addition, myristic acid from Myristica fragrans was able to inhibit hyphal mediated biofilm formation in Candida albicans by regulating proteins involved in lipid rafting. Furthermore, another bioactive compound was found to inhibit extracellular polysaccharide, lipase, motility and cell surface hydrophobicity of Acinetobacter baumannii by targeting the QS based virulence factors. Thus, these novel anti-virulent agents could be clinically utilized to control infections caused by antibiotic resistant pathogens.