Ebselen’s Potential to Inhibit Planktonic and Biofilm Growth of Neisseria mucosa

Abstract

Background: Antibiotic resistance of various bacterial communities remains a global burden in the healthcare industry. Biofilm formation is one of the resistance mechanisms acquired by bacterial communities in order to reverse the action of antibiotics. There is an urgent need for the discovery of novel antimicrobials and novel approaches to tackle this problem. However, it is very expensive and challenging to develop new antibiotics. Drug repurposing is an efficient strategy which reduces time and cost associated with drug discovery. Objective: In the current study, anti-microbial and antibiofilm potential of an organoselenium clinical molecule Ebselen against Neisseria mucosa has been elucidated. Methods: Ebselen Antibacterial studies include Minimum Inhibitory Concentration (MIC), growthkill, Colony Forming Unit (CFU) assays and intracellular Reactive Oxygen Species (ROS) accumulation studies. Antibiofilm studies included inhibition, eradication and cell surface hydrophobicity assays, quantification of Extracellular Polymeric Substance (EPS) and eDNA and for anti-quorum sensing activity, protease and urease enzyme activities were elucidated. Results: Ebselen showed efficient bactericidal activity as indicated by its low MIC values, bacterial growth inhibition over time and its ability to prevent clonal propagation in this bacterium. Increased accumulation of ROS in Ebselen treated cells indicates radical mediated induction of bacterial death. Interestingly, Ebselen inhibited and distorted matured biofilms by degrading the eDNA component of the EPS layer. Ebselen also attenuated quorum-sensing pathway as indicated by decreased urease and protease enzyme activities. Conclusion: Taken together, these results paved the way to repurpose Ebselen as a potential drug target to curb Neisseria mucosa infections.