Empowering antimicrobial photodynamic therapy of Staphylococcus aureus infections with potassium iodide

Infections caused by the Gram-positive bacterium Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), impose a great burden on global healthcare systems. Thus, there is an urgent need for alternative approaches to fight staphylococcal infections, such as targeted antimicrobial photodynamic therapy (aPDT). We recently reported that targeted aPDT with the S. aureus-specific immunoconjugate 1D9-700DX can be effectively applied to eradicate MRSA. Nonetheless, the efficacy of aPDT in the human body may be diminished by powerful antioxidant activities. In particular, we observed that the efficacy of aPDT with 1D9-700DX towards MRSA was reduced in human plasma. Here we show that this antagonistic effect can be attributed to human serum albumin, which represents the largest pool of free thiols in plasma for trapping reactive oxygen species. Importantly, we also show that our targeted aPDT approach with 1D9-700DX can be empowered by the non-toxic inorganic salt potassium iodide (KI), which reacts with the singlet oxygen produced upon aPDT, resulting in the formation of free iodine. The targeted iodine formation allows full eradication of MRSA (more than 6-log reduction) without negatively affecting other non-targeted bacterial species or human cells. Altogether, we show that the addition of KI allows a drastic reduction of both the amount of the immunoconjugate 1D9-700DX and the irradiation time needed for effective elimination of MRSA by aPDT in the presence of human serum albumin.