Synergistic gentamicin-photodynamic therapy against resistant bacteria in burn wound infections

Multi-resistant bacteria, partially a result of the abuse of antibiotics, have greatly diminished the effectiveness of antibiotics. The combination of antibiotics with other therapies like antimicrobial photodynamic therapy (aPDT) may provide a useful strategy for fighting resistant bacteria. Here, the synergistic bactericidal effects of toluidine blue (TB)-aPDT and gentamicin (GEN) were evaluated in vitro and in vivo.

The Post-antibacterial effects were measured at 600 nm (OD600) by a microplate reader. The bacterial envelope and biofilm were observed by a field emission scanning electron microscope. The expression of oxidative stress and Agr system-related genes was analyzed by qRT-PCR after GEN combined with TB-aPDT (GEN&aPDT). Besides, the burn infection model was established to investigate the cloning efficiency of immobilized bacteria, wound healing and inflammatory factors in the lesions.

GEN&aPDT could inhibit the growth of Staphylococcus aureus (S. aureus) and multidrug-resistant S. aureus (MDR S. aureus) for up to 15 h, and destroyed the cell envelope and biofilm structure of S. aureus and MDR S. aureus. During the process, ROS played an important role, inducing oxidative stress and downregulating the expression of AgrA, AgrB and PSM in the Agr system, resulting in decreased bacterial virulence and infectivity. In addition, GEN&aPDT cotreatment could effectively promoted wound healing in burn-infected mice by reducing the numbers of bacterial colonization in the wound, decreasing the content of inflammatory factors, and increasing the expression of growth factors.

The present study confirmed a bactericidal synergy between GEN and aPDT in vitro and in vivo, therein, the oxidative stress exhibited an important role in decreasing bacterial virulence and infectivity, which may bring new ideas for the treatment of bacterial resistance.