Biocompatible Rhamnolipid Self-Assemblies with pH-Responsive Antimicrobial Activity

There is an urgent need for alternative antimicrobial materials due to the growing challenge of bacteria becoming resistant to conventional antibiotics. This study demonstrates the creation of a biocompatible pH-switchable antimicrobial material by combining bacteria-derived rhamnolipids (RL) and food-grade glycerol monooleate (GMO). The integration of RL into dispersed GMO particles, with an inverse-type liquid crystalline cubic structure in the core, leads to colloidally stable supramolecular materials. The composition and pH-triggered structural transformations are studied with small-angle X-ray scattering, cryogenic transmission electron microscopy, and dynamic light scattering. The composition-structure-activity relationship is analyzed and optimized to target bacteria at acidic pH values of acute wounds. The new RL/GMO dispersions reduce Staphylococcus aureus (S. aureus) populations by 7-log after 24 h of treatment with 64 mu g mL-1 of RL and prevent biofilm formation at pH = 5.0, but have no activity at pH = 7.0. Additionally, the system is active against methicillin-resistant S. aureus (MRSA) with minimum inhibitory concentration of 128 mu g mL-1 at pH 5.0. No activity is found against several Gram-negative bacteria at pH 5.0 and 7.0. The results provide a fundamental understanding of lipid self-assembly and the design of lipid-based biomaterials, which can further guide the development of alternative bio-based solutions to combat bacteria. This study introduces a pH-responsive antimicrobial nanomaterial made from bio-derived rhamnolipids and glycerol monooleate. pH- and composition-triggered colloidal transformations are reported and optimized for antimicrobial performance. The material kills Staphylococcus aureus and methicillin-resistant Staphylococcus aureus at pH 5.0 but not at pH 7.0. Furthermore, it inhibits Staphylococcus aureus biofilm formation. The nanomaterial shown biocompatible with human dermal fibroblasts.image