Combating planktonic and biofilm growth of Serratia marcescens by repurposing ebselen

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Abstract
Aim of the study The rising instances of multidrug-resistant pathogens are rapidly evolving into a global healthcare crisis. Identifying new ways of synthesis of antibiotics is both time-consuming and expensive. Repurposing existing drugs for the treatment of such antimicrobial-resistant pathogens has also been explored. Methods and results In the current study, ebselen was screened for antibacterial and antibiofilm activity against Serratia marcescens. Various antibacterial studies such as minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), time-kill curves, intracellular reactive oxygen species (ROS) quantification, and colony-forming unit assays were performed. The antibiofilm potential was assayed by biofilm inhibition, cell surface hydrophobicity assay, eradication, quantification of extracellular DNA (eDNA), and extracellular polymeric substance (EPS) layer and scanning electron microscopy (SEM) analysis were performed. Anti-quorum sensing assay was validated by quantifying the virulence factors production. Further molecular docking of ebselen with two quorum sensing (QS) specific proteins was also carried out. Antibacterial susceptibility tests showed potent antimicrobial activity of ebselen against S. marcescens with MIC50 of 14 μg/mL. Ebselen’s ability to disturb the redox environment by inducing significant ROS generation led to bacterial death. It also showed concentration-dependent bactericidal activity as indicated by reduced bacterial growth and colony-forming unit propagation. Ebselen was also found to prevent biofilm attachment by altering the cell surface hydrophobicity while also being effective against preformed biofilms as validated by scanning electron microscopy (SEM) analysis. Additionally, ebselen showed reduced virulence factors like urease enzyme activity and prodigiosin pigment production indicating its promising anti-quorum sensing potential. Molecular docking analysis validated the strong binding of ebselen with QS-specific proteins (1Joe and PigG) with binding energies of − 6.6 and − 8.1kj/mol through hydrogen bonds and aromatic interactions. These results show that ebselen has potent antibiofilm potential that can be explored to identify treatment against bacterial infections.

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