Fighting Staphylococcus aureus infections with light and photoimmunoconjugates

Mafalda Alves Fernandes Bispo, Andrea Anaya Sánchez, Sabrina Suhani, Elisa Raineri, Marina Lopez Alvarez, Marjolein Heuker, Wiktor Szymanski, Francisco Romero Pastrana, Girbe Buist, Alexander R. Horswill, Kevin P. Francis, Go Dam, van, Marleen Oosten, van, Jan Maarten Dijl, van*

*Corresponding author for this work

Research output: Contribution to journalArticleProfessional

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Abstract

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.

Original languageEnglish
Article number139512
Number of pages17
JournalJCI Insight
Issue number22
DOIs
Publication statusPublished - 19-Nov-2020

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