GC-MS unveils monosaccharide D-Allose in Terminalia arjuna bark extract acting against biofilm regulatory proteins (SrtA and SarA) of Staphylococcus aureus: A drug discovery approach

Abstract

The rising prevalence of biofilm-related infections and foodborne diseases, particularly those caused by Staphylococcus aureus, presents significant challenges to conventional treatment strategies due to the increasing phenomenon of antibiotic resistance caused by biofilm. In response, this study employed GC-MS analysis of the methanolic and n-hexane extracts of Terminalia arjuna bark, a traditional medicinal plant, and identified a diverse array of bioactive compounds. All 79 compounds identified from GC-MS data were examined to determine the best binding score with SrtA and SarA, two key proteins involved in the development of biofilms and the pathogenicity of Staphylococcus aureus. Among 79 compounds, D-Allose, a monosaccharide, demonstrated the best binding affinity with SrtA (−6.304 kcal/mol) by involving five hydrogen bonds and SarA (−5.101 kcal/mol) by involving three hydrogen bonds, compared to other compounds among 158 interactions. Molecular dynamics and simulations were performed for 100 ns to analyze the interaction parameters with SrtA and SarA. Corresponding MM-GBSA binding energy values were −33.66 kcal/mol (D-Allose with SrtA), −18.09 kcal/mol (D-Allose with SarA). The fact that D-Allose has zero violations of Lipinski's Rule of Five further exemplifies its suitability as a medication candidate. These interactions suggest that D-Allose may interfere with bacterial adhesion, quorum sensing, and the synthesis of the biofilm matrix by interacting with SrtA and SarA. To the best of our knowledge, this is the first study to elucidate the potential mechanism by which D-Allose exerts its antibiofilm activity. Future research on in vitro and in vivo studies should focus on experimental validation to establish D-Allose as a promising monosaccharide candidate for combating biofilm-related antibiotic-resistant Staphylococcus aureus infections.