Zwitterionic derivatization of rhamnolipids: An efficient and biologically friendly antibacterial agent

The development of efficient and biocompatible antibacterial agents is crucial to address multidrug resistance resulting from the abundant abuse of antibiotics; however, this endeavor remains challenging. This study prepared a zwitterionic rhamnolipid derivative (di-RLs-Arg-OH) containing both guanidine and carboxyl groups via amide condensation and demethylation reactions. This new derivative manifested improved antibacterial activity and reduced cytotoxicity against blood and NIH/3T3 cells compared with di-rhamnolipids. The MIC of di-RLs-Arg-OH against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) was lowered to 32–256 mg/L, while the HC 50 was as high as 917 mg/L. The involved mechanism might be attributed to the zwitterionic property of di-RLs-Arg-OH, which contains both carboxyl and guanidine groups. The findings in the present study facilitate the design of biosurfactant-based derivatives as bio-friendly antibacterial agents.