Executive Summary : | Diabetic foot ulcers (DFU) are a significant complication of diabetes, exacerbated by microbial infection. These ulcers are polymicrobial in nature, and understanding the interactions between microbial pathogens and their hosts can improve wound healing and management. Extracellular vesicles (EVs) have been recognized as key mediators of host-pathogen interactions, contributing to various roles such as transporting biologically important molecules, pathogen survival, virulence, antibiotic resistance, biofilm formation, and immune regulation. EVs are released by both microbes and hosts, making them attractive candidates for investigating microbe-microbe and microbe-host communications. RNA, a key component of EV cargo, is of great importance due to its immunomodulatory properties. However, there are still unanswered questions about EV RNA's role in polymicrobial communication, interaction with host cells, host gene targets, and pathogen survival. The study aims to isolate and characterize RNA from EVs produced during microbial interactions in DFU, analyze their effects on host cells and other target microorganisms, and study the impact of EVs on infection severity and wound closure using an in vivo animal model. This will provide mechanistic insights into potential gene pathways involved in biogenesis, communication, and regulation of host immunity via EVs, helping design efficacious, target-specific EVs and novel antibiotics. Exploring the immune responses elicited by EVs can also help design EVs with RNA content that can trigger desirable immune responses in the host. |