Investigation of the Antibacterial Mechanisms and Anti-biofilm Formation of Coronarin D against Staphylococcus Pathogens: A Molecular Docking Approach

The effect of coronarin D on staphylococcal bacteria has been researched in the past. However, the mechanisms of action and the inhibitory effect on biofilm formation have not been investigated. Therefore, the primary aim of this study was to explore the antibacterial mechanism of coronarin D against Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis), including its molecular docking interactions with bacterial membranes. Our initial approach involved conducting antibacterial tests using microdilution methods. Furthermore, we utilized the LIVE/DEAD BacLight bacterial viability assay and cell leakage analysis to evaluate the impact of coronarin D on the integrity of the bacterial membrane. Molecular docking investigations were carried out using AutoDock 4.2 software. Coronarin D exhibited a dose- and time-dependent antibacterial effect, with increased concentrations (12.5 to 25 μg/mL) leading to more rapid and extensive bacterial cell death over a 24-hour period. Specifically, the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) for both Staphylococcus species were determined at 12.5 μg/mL and 25 μg/mL, respectively. Noteworthy findings from molecular docking studies revealed significant interactions between coronarin D and bacterial membrane proteins, particularly through hydrogen bonding and hydrophobic interactions with key residues in proteins X and Y. These interactions suggest that coronarin D may disrupt membrane integrity, contributing to its antibacterial action. In addition, coronarin D demonstrated inhibitory effects on biofilm formation at sub-MIC concentrations (0.25MIC), reducing biofilm formation by 34.17% in S. aureus and 43.63% in S. epidermidis, despite no reduction in viable bacterial counts at this concentration. The compound also showed slight to moderate toxicity on human epidermal keratinocyte (HaCaT) cells, with a half-maximal inhibitory concentration (IC50) of 41.358 µg/mL, indicating a moderate safety margin compared to other known antimicrobials. These findings highlight coronarin D's potential as a potent antibacterial agent against Staphylococcus spp., offering promising avenues for managing Staphylococcal infections, particularly those involving biofilm-associated resistanceF.

Investigation of the Antibacterial Mechanisms and Anti-biofilm Formation of Coronarin D against Staphylococcus Pathogens: A Molecular Docking Approach Keywords:

Antibacterial mechanisms , Anti-Biofilm Formation , Coronarin D , Staphylococcus pathogens , Molecular docking