Natural Inhibitors from Ganoderma lucidum Targeting BlaR1 Resistant Staphylococcus aureus in Athlete Skin Disease

Abstract

Introduction: Skin infections caused by Beta-lactam-resistant Staphylococcus aureus are a concern among athletes because they spread rapidly through skin contact. These infections can interfere with performance, delay training, and affect the team's overall health, making them a significant problem in the world of sports. This study explores the potential of secondary metabolites from Ganoderma lucidum as candidates for BlaR1 inhibitors, which can be a new approach to overcome the resistance mechanism in Staphylococcus aureus. Methods: 324 secondary metabolites from G. lucidum were downloaded from KNAPSACK. Drug pharmacokinetic evaluation was performed using SwissADME based on Lipinski’s Rule of Five, while acute toxicity prediction in mice was performed using the GUSAR and QSAR platforms. Compounds that met the criteria for drug pharmacokinetics and non-toxicity were then further analyzed through molecular docking simulations against the BlaR1 protein (PDB ID: 1XA1).  Results: The results showed that 26% (n=87/324) of metabolites met Lipinski's criteria and 4% (n=14/324) were predicted to be non-toxic. Based on the docking results, Lucidenic acid F was identified as the most potential candidate to inhibit antibiotic-resistant Staphylococcus aureus, with a binding affinity of -7.4 kcal/mol at the active site of BlaR1 protein. Conclusions: Lucidenic acid F has the potential to support future therapeutic development against skin disease in athletes caused by beta-lactam-resistant S. aureus. Further studies are needed in vitro and in vivo to evaluate the safety of Lucidenic acid F when applied clinically.