Oxidized pullulan exhibits potent antibacterial activity against S. aureus by disrupting its membrane integrity

The capability of bacteria to withstand the misuse of antibiotics leads to the generation of multi-drug resistant strains, posing a new challenge to curb wound infections. The biological macromolecules, due to their biocompatibility, biodegradability, and antimicrobial properties, have been explored for a variety of antimicrobial and therapeutic purposes. This work reports that a single-step oxidation of pullulan polymer leads to the formation of oxidized pullulan (o-pullulan), which shows striking antibacterial and antibiofilm activities against the Gram-positive bacteria, Staphylococcus aureus, implicated in wound-related infections. Oxidation of pullulan generates 28 % aldehyde groups (3.462 mmol/g) which exerted 97 % bactericidal activity against S. aureus by targeting cell wall-associated membrane protein SpA (Staphylococcal protein A). The molecular docking, gene silencing, and fluorescence quenching studies revealed a direct binding of o-pullulan with the B and C domains of SpA, which alters the membrane potential and inhibits Ca²⁺-Mg²⁺-ATPase pumps. O-pullulan also exhibited scavenging activity against intracellular reactive oxygen species (ROS), and non-immunotoxic activity and was found to be non-toxic to mammalian cells. Thus, o-pullulan shows great promise as an antimicrobial polymer against S. aureus for chronic wound management.