Search

Pseudomonas aeruginosa is the second most emerging multidrug-resistant, opportunistic pathogen after Acinetobacter baumannii that poses a threat in nursing homes, hospitals, and patients who need devices such as ventilators and blood catheters. Its ability to form quorum sensing-regulated virulence factors and biofilm makes it more resistant to top most therapeutic agents such as carbapenems and next-generation antibiotics. In the current study, we studied the quorum quenching potential of secondary metabolites of Mycoleptodiscus indicus PUTY1 strain. In vitro observation showed a mitigation in virulence factors such as rhamnolipids, protease, elastase pyocyanin, exopolysaccharides, and hydrogen cyanide gas. Furthermore, a significant reduction in the motility such as swimming, swarming, twitching, and inhibition in biofilm formation by Pseudomonas aeruginosa PAO1 was observed. Results of in vitro studies were further confirmed by in silico studies through docking and molecular dynamic simulation of GC-MS-detected compounds of Mycoleptodiscus indicus employing LasR and RhlR proteins. Both in vitro and in silico observations indicate a new alternative approach for combating virulence of Pseudomonas aeruginosa by targeting its protein receptors LasR and RhlR. Graphical abstract.

Pseudomonas aeruginosa is an opportunistic nosocomial pathogenic microorganism causing majority of acute hospital-acquired infections and poses a serious public health concern. The persistence of bacterial infection can be attributed to the highly synchronised cell-to-cell communication phenomenon, quorum sensing (QS) which regulates the expression of a number of virulence factors and biofilm formation which eventually imparts resistance to the conventional antimicrobial therapy. In this study, the anti-quorum sensing and anti-biofilm potential of ferulic acid encapsulated chitosan-tripolyphosphate nanoparticles (FANPs) was investigated against P. aeruginosa PAO1 and compared with native ferulic acid. Dynamic light scattering and transmission electron microscopic analysis confirmed the synthesis of FANPs with mean diameter of 215.55 nm. FANPs showed significant anti-quorum sensing activity by downregulating QS-regulated virulence factors. In addition, FANPs also significantly attenuate the swimming and swarming motility of P. aeruginosa PAO1. The anti-biofilm efficacy of FANPs as compared to native ferulic acid was established by light and confocal laser scanning microscopic analysis. The promising results of FANPs in attenuating QS highlighted the slow and sustained release of ferulic acid at the target sites with greater efficacy suggesting its application towards the development of anti-infective agents.

Pseudomonas aeruginosa is an opportunistic nosocomial pathogen causing the majority of acute and persistent infections in human beings. The ability to form biofilm adds a new dimension to its resistance to conventional therapeutic agents. In the present study, down-regulation of quorum sensing regulated virulence and biofilm development resulting from exposure to Aspergillus ochraceopetaliformis SSP13 extract was investigated. The in vitro results inferred impairment in the production of LasA protease, LasB elastase, chitinase, pyocyanin, exopolysaccharides and rhamnolipids. In addition, motility and biofilm formation by P. aeruginosa PAO1 was significantly altered. The in vitro results were further supported by molecular docking studies of the metabolites obtained from GC-MS analysis depicting the quorum sensing attenuation by targeting the receptor proteins LasR and RhlR. The in vitro and in silico studies suggested new avenues for the development of bioactive metabolites from A. ochraceopetaliformis SSP13 extract as potential anti-infective agents.

Pseudomonas aeruginosa is an important opportunistic pathogen which causes bacterial keratitis, cyctic fibrosis and other hospital acquired infections. Its ability to form biofilm provides resistance to conventional antibiotics and further corroborates the global health concerns. The antibiotic resistance by P. aeruginosa is due to highly complex cellular signaling system called quorum sensing (QS). As QS controls bacterial pathogenicity and plays a crucial role in biofilm formation, it is a promising alternative target to combat the bacterial virulence. The present study aims to determine the inhibitory activity of Plectranthus tenuiflorus extract on QS and biofilm development in P. aeruginosa PAO1. The crude plant extract inhibited the production of pyocyanin, elastase, protease and chitinase by 71.96 ± 1.82, 38.74 ± 1.29, 30.84 ± 1.20 and 44.75 ± 1.40 % respectively at sub-MIC concentration of 500 µg/ml. The production of biofilm aggravating phenotypes such as exopolysaccharides, alginate and rhamnolipid were also significantly reduced. The biofilm inhibition capability of P. tenuiflorus was further supported by light microscopic and confocal laser scanning microscopic analysis. The phytochemicals such as phytol and mosloflavone were identified from the crude extract using gas chromatography–mass spectrometry (GC-MS). The role of these phytochemicals in down regulation of QS in P. aeruginosa was further confirmed by in silico studies targeting transcriptional receptors, LasR and RhlR of the QS regulatory network. The in vitro and docking studies suggest the anti QS potential of P. tenuiflorus in combating the bacterial pathogenesis.

Objective: To investigate the antioxidant and anti-infective potential of Phrynium capitatum and Dryptes indica extract. Methods: The antioxidant potentials were determined by DPPH radical scavenging, reducing power, hydroxyl radical scavenging and total antioxidant assays. We further examined anti-quorum sensing activity and inhibition of synthesis of pathogenic factor of Chromobacterium violaceum and Pseudomonas aeruginosa PAO1. Bioactive compounds were determined using gas chromatography–mass spectrometry analysis. In silico analysis was conducted to determine the binding affinity of bioactive compounds of plant extracts for the quorum sensing regulatory receptor LasR. Results: DPPH assay showed that the ethanolic extract of Phrynium capitatum and Dryptes indica at 500 μg/mL showed (86.96 ± 4.07)% and (74.83 ± 3.47)% inhibition, respectively. Hydroxyl radical scavenging assay showed (73.17 ± 3.03)% and (62.63 ± 4.59)% activity, respectively. The ethanolic extract of Phrynium capitatum and Dryptes indica showed high level of attenuation of quorum sensing regulated pyocyanin production. Confocal laser scanning microscopic analysis revealed that the extracts had the potential to effectively inhibit biofilm formation of Pseudomonas aeruginosa. Molecular docking analysis showed a better binding affinity of bioactive compounds from the extracts for the structure of LasR protein of Pseudomonas aeruginosa. Conclusions: The ethanolic extracts of Phrynium capitatum and Dryptes indica possess antioxidant activity and the potential to inhibit the quorum sensing system and its regulatory irulence traits in Pseudomonas aeruginosa PAO1. [ABSTRACT FROM AUTHOR]