Inhibition of quorum sensing–associated virulence factors and biofilm formation in Pseudomonas aeruginosa PAO1 by Mycoleptodiscus indicus PUTY1

Abstract

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.

Quorum Sensing Mediated Pathogenicity, Virulence Genes and Class 1 Integron in Carbapenem-Resistant Clinical Pseudomonas Aeruginosa Isolates

“…Bacteria with QS systems that govern virulence factors and bio lm formation are more resistant to most treatment agents, such as carbapenems and next-generation antibiotics (Tanveer et al, 2020). The present study results supported this viewpoint to some extent.…”

“…In the present study, two QS system genes were detected in almost all isolates (98.7%) and compared with the presence of the two QS system genes, the percentage of las system genes (98.07%) were higher than that of rhl system genes (90.38%). In addition, there was a positive correlation between two QS system genes (p < .10 Bacteria with QS systems that govern virulence factors and bio lm formation are more resistant to most treatment agents, such as carbapenems and next-generation antibiotics (Tanveer et al, 2020). The present study results supported this viewpoint to some extent.…”

Subinhibitory Concentrations of Biogenic Silver Nanoparticles Affect Motility and Biofilm Formation in Pseudomonas aeruginosa

“…Due to the increase in multidrug resistance to antimicrobials, several studies have been carried out searching for new alternatives to interfere in the regulation of bacterial virulence and control the spread of multidrug-resistant bacteria ( Shah et al., 2019 ; Ahmed et al., 2020 ; Piewngam et al., 2020 ). A major concern is that in these studies, subinhibitory concentrations of the compounds are used and we do not know for sure the bacterial response to these nanometals.…”

Quorum Sensing Inhibiting Activity of Cefoperazone and Its Metallic Derivatives on Pseudomonas aeruginosa

“…The hydrogen bonds between the polar groups of the acyl-homoserine lactone and residues Tyr56, Trp60, Asp73, and Ser129 of LasR are pivotal for the correct folding of LuxR protein (Monterrosa et al, 2019;Prateeksha et al, 2019;Hnamte et al, 2020). Ahmed and coauthors elucidate the binding of 3-oxo-C12-HSL with LasR via hydrogen bonds with Tyr56, Trp60, and Asp73 (Ahmed et al, 2020). In our study, 10 hydrogen bonds were formed between CFP and LasR receptor at Tyr47, Tyr64, Thr75, Ala50, Gly126, and Arg61 residues.…”