TY - JOUR AU - Bispo, Mafalda AU - Anaya-Sanchez, Andrea AU - Suhani, Sabrina AU - Raineri, Elisa J. M. AU - López-Álvarez, Marina AU - Heuker, Marjolein AU - Szymański, Wiktor AU - Romero Pastrana, Francisco AU - Buist, Girbe AU - Horswill, Alexander R. AU - Francis, Kevin P. AU - van Dam, Gooitzen M. AU - van Oosten, Marleen AU - van Dijl, Jan Maarten T1 - Fighting Staphylococcus aureus infections with light and photoimmunoconjugates PY - 2020/11/19/ AB - Infections caused by multidrug-resistant Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), are responsible for high mortality and morbidity worldwide. Resistant lineages were previously confined to hospitals but are now also causing infections among healthy individuals in the community. It is therefore imperative to explore therapeutic avenues that are less prone to raise drug resistance compared with today’s antibiotics. An opportunity to achieve this ambitious goal could be provided by targeted antimicrobial photodynamic therapy (aPDT), which relies on the combination of a bacteria-specific targeting agent and light-induced generation of ROS by an appropriate photosensitizer. Here, we conjugated the near-infrared photosensitizer IRDye700DX to a fully human mAb, specific for the invariantly expressed staphylococcal antigen immunodominant staphylococcal antigen A (IsaA). The resulting immunoconjugate 1D9-700DX was characterized biochemically and in preclinical infection models. As demonstrated in vitro, in vivo, and in a human postmortem orthopedic implant infection model, targeted aPDT with 1D9-700DX is highly effective. Importantly, combined with the nontoxic aPDT-enhancing agent potassium iodide, 1D9-700DX overcomes the antioxidant properties of human plasma and fully eradicates high titers of MRSA. We show that the developed immunoconjugate 1D9-700DX targets MRSA and kills it upon illumination with red light, without causing collateral damage to human cells. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.139512 VL - 5 IS - 22 UR - https://doi.org/10.1172/jci.insight.139512 PB - The American Society for Clinical Investigation ER -