Study on the Role of Human Gut Microbiome in Controlling MRSA-Induced Sepsis Using Proteomics Tool

Background: Sepsis is defined as the extreme response of a body to an infection, leading to untimely death if left untreated. The human gut microbiome is characterized by the presence of several microorganisms in the gastrointestinal tract. This study provides insight into the potential therapeutic effects of a peptide present in the human gut microbiome that helps control sepsis. Aim: This study aimed to explore the therapeutic application of a peptide from Lactobacillus sp. in the human gut microbiome as an alternative to MRSA, which causes severe, fatal diseases like sepsis. It also elucidates the peptide-protein interactions that enhance the efficacy of infection control and treatment. Objectives: We aimed to investigate the interactions between protein-peptide and protein-drug complexes through in silico analyses. Methods: Molecular docking was performed using PyRx and HADDOCK tools. Next, we performed molecular simulation studies using GROMACS v2020.6 at different physiological pH values of 4, 6, and 7.4. Stability, compactness, and binding energies were analyzed using parameters such as RMSD, Rg, and MMPBSA, among other parameters. Results: We observed stability on docking between Plantaricin KL-1Y, an effective bacteriocin from Lactobacillus plantarum (organism from gut microbiome), and PBP2a from Staphylococcus aureus (causative organism of sepsis). This was indicated by a binding affinity of -13.4 kcal/mol, higher than that of PBP2a-FDA-approved drug (-8 kcal/mol). The MMPBSA results of the PBP2a- Plantaricin KL-1Y complex showed a significantly higher binding affinity at pH 7.4 of -228.451 kcal/mol in comparison to -69.5747 kcal/mol for the PBP2a-Ceftaroline fosamil complex. Conclusion: These results indicate the possible use of a peptide from the human gut as a potential therapeutic agent against S. aureus infection.