In Silico Hybridization and Molecular Dynamics Simulations for the Identification of Candidate Human MicroRNAs for Inhibition of Virulent Proteins' Expression in Staphylococcus aureus.

Abstract

Staphylococcus aureus is a major threat to human health, causing infections that range in severity from moderate to fatal. The rising rates of antibiotic resistance highlight the critical need for new therapeutic techniques to combat this infection. It has been recently discovered that microRNAs (miRNAs) are essential for cross-kingdom communication, especially when it comes to host-pathogen interactions. It has been demonstrated that these short noncoding RNAs control gene expression in the gut microbiota, maintaining homeostasis; dysbiosis in this system has been linked to several diseases, including cancer. Our research attempts to use this understanding to target specific bacterial species and prevent severe diseases. In particular, we look for putative human miRNAs that can attach to virulent bacterial proteins' mRNA and prevent them from being expressed. In-silico hybridization experiments were performed between 100 human miRNA sequences with varied expression levels in gram-positive bacterial infections and five virulence factor genes. In addition, these miRNAs' binding properties were investigated using molecular dynamics (MD) simulations. Our findings demonstrate that human miRNAs can target and inhibit the expression of bacterial virulent genes, thereby opening up new paths for developing innovative miRNA-based therapeutics. The implementation of MD simulations in our study not only improves the validity of our findings but also proposes a new method for constructing miRNA-based therapies against life-threatening bacterial infections.