Targeting the phosphatidylglycerol lipid: An amphiphilic dendrimer as a promising antibacterial candidate

The rapid emergence and spread of multidrug-resistant bacterial pathogens require the development of antibacterial agents that are robustly effective while inducing no toxicity or resistance development. In this context, we designed and synthesized amphiphilic dendrimers as antibacterial candidates. We report the promising potent antibacterial activity shown by the amphiphilic dendrimer , composed of a long hydrophobic alkyl chain and a tertiary amine-terminated poly(amidoamine) dendron, against a panel of Gram-negative bacteria, including multidrug-resistant and exhibited effective activity against drug-resistant bacterial infections in vivo. Mechanistic studies revealed that targeted the membrane phospholipids phosphatidylglycerol (PG) and cardiolipin (CL), leading to the disruption of the bacterial membrane and proton motive force, metabolic disturbance, leakage of cellular components, and, ultimately, cell death. Together, that specifically interacts with PG/CL in bacterial membranes supports the use of small amphiphilic dendrimers as a promising strategy to target drug-resistant bacterial pathogens and addresses the global antibiotic crisis.