Role of Nocardia sp. bioactives in regulating the key molecular checkpoints in quorum-sensing pathways of P. aeruginosa: application towards improved fabrication of medical devices

Understanding the inhibitory role of bioactives from a novel Nocardia sp. against P. aeruginosa's Quorum-Sensing (QS) regulatory pathways and fabrication of effective foley catheters. P. aeruginosa‘s antimicrobial resistance is due to its biofilm formation, which reduces drug efficacy. Nocardia sp. has emerged as significant genus that produces bioactives with inhibitory effects on the biofilm. Samples from a termite nest were used to isolate rare actinomycetes, which were tested to inhibit biofilm formation by the pathogen P. aeruginosa PAO1. Molecular interactions and regulatory effects were investigated using various techniques. The study details a new strain from the rare actinobacterial genus Nocardia sp., isolated from a termite nest known for its bioactive potential. The isolate's bioactive preparations inhibited P. aeruginosa biofilm formation by 86.4% without affecting growth. The significant compounds of the crude extract identified by GC-MS were docked against LasR, RhlR, and PQS (QS proteins), which showed high binding scores. The downregulation of QS system genes like lasA, lasB, rhlA, rhlB, and pqsA supports the idea that secondary metabolites act on the two main regulators of the QS. The bioactives also inhibited virulent factors viz., pyocyanin, pyoverdine, rhamnolipid, and proteases by 51.2, 81, 27.2 and 62.1%, respectively Finally, the bioactive preparation showed the potential to inhibit biofilm formation on catheters. The study indicates that Nocardia sp. produces compounds that can reduce biofilm formation in P. aeruginosa by targeting the QS-controlled pathogenicity. This research can benefit medical devices like catheters to resist contamination in clinical settings.