Prostaglandin E2 attenuates synergistic bactericidal effects between COX inhibitors and antibiotics on Staphylococcus aureus.

PGE2 is found to attenuate the bactericidal effects of kanamycin or ampicillin in Staphylococcus aureus, as well as the methicillin-resistant S. aureus (MRSA). Co-treatment with cyclooxygenase (COX) inhibitors (celecoxib, aspirin or naproxen) synergistically enhances kanamycin or ampicillin-induced cell death of S. aureus and MRSA. COX inhibitors repressed bacterial multidrug resistance through down-regulating efflux pump activity in antibiotics-treated S. aureus and MRSA. However, this synergistic bactericidal effects are reduced by the treatment with PGE2. PGE2 restores the efflux pump activity as well as increases biofilm formation in S. aureus and MRSA. Collectively, the enhancement of efflux pump activity and biofilm formation with PGE2 might partially explain the resistance to synergistic bactericidal effects between COX inhibitors and antibiotics in PGE2-treated S. aureus.

Concentration-dependent dual effects of silibinin on kanamycin-induced cells death in Staphylococcus aureus.

Silibinin has dual effects on bacteria, depending on the concentrations or living contexts. The mechanism of either action has not yet been elucidated. Present study suggests that silibinin has yinyang impacts on the growth of Staphylococcus aureus depending on doses. S. aureus treated with low concentration of silibinin (L, 6.2 µM) showed enhanced resistance to kanamycin through increased level of hydrogen peroxide (H2O2). However, S. aureus treated with medium concentration of silibinin (M, 50 µM) showed increased susceptibility to kanamycin through reduced level of H2O2. These findings suggested that dual effects of silibinin were concentration-dependent and apparently related to the levels of H2O2 that assist bacterial survival at higher concentrations. Interestingly, treatment with high concentration of silibinin (H, 400 µM) alone without kanamycin exhibited cytotoxicity to S. aureus regardless of H2O2 levels. Based on the findings in vitro, we moved to examine the influence of silibinin on S. aureus-induced mouse peritonitis model. Silibinin at high concentration was shown to enhance the survival of peritonitis mice and protected them from S. aureus-induced tissue injury presumably by antibacterial effect of high concentration of silibinin. When the infected mice were co-treated with kanamycin, bacterial burden and H2O2 levels in lung, liver and spleen were all increased by treatment with a low dose of silibinin, while decreased with a medium dose of silibinin. Thus, the findings highlighted the potential of silibinin to be as a modifying agent in case of antibiotic resistance.

Salicylate induces reactive oxygen species and reduces ultraviolet C susceptibility in Staphylococcus aureus.

This study demonstrates that growth of Staphylococcus aureus in the presence of salicylate reduces ultraviolet C (UVC)-induced cell death and increases the generation of reactive oxygen species (ROS). In addition, compounds that scavenge ROS (N-acetylcysteine, glutathione, catalase and superoxide dismutase) reverse the increased UVC survival induced by growth in the presence of salicylate, while ROS donors (tert-butylhydroperoxide, H2O2 and NaClO) enhance survival of salicylate challenged cultures. Collectively, these findings suggest that ROS production induced by growth in the presence of salicylate protects S. aureus from UVC-induced cell death.