Harnessing light-activated gallium porphyrins to combat intracellular Staphylococcus aureus using an in vitro keratinocyte infection model
Abstract Staphylococcus aureus (S. aureus) can survive inside nonprofessional phagocytes such as keratinocytes, enabling it to evade antibiotics and cause recurrent infections once treatment stops. New antibacterial strategies to eliminate intracellular, multidrug-resistant bacteria are needed. This...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-84312-4 |
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| author | Klaudia Szymczak Michał Rychłowski Lei Zhang Joanna Nakonieczna |
| author_facet | Klaudia Szymczak Michał Rychłowski Lei Zhang Joanna Nakonieczna |
| author_sort | Klaudia Szymczak |
| collection | DOAJ |
| description | Abstract Staphylococcus aureus (S. aureus) can survive inside nonprofessional phagocytes such as keratinocytes, enabling it to evade antibiotics and cause recurrent infections once treatment stops. New antibacterial strategies to eliminate intracellular, multidrug-resistant bacteria are needed. This study used a keratinocyte model infected with methicillin-resistant S. aureus (MRSA) to test light-activated compounds, specifically heme-mimetic gallium (III) porphyrin (Ga3+CHP) and visible light, known as antimicrobial photodynamic inactivation (aPDI), for eliminating intracellular MRSA. Ga3+CHP was found to accumulate more in infected cells, particularly within lysosomal structures where MRSA resides. Flow cytometry and fluorescence microscopy revealed significant colocalization of MRSA and Ga3+CHP. Under aPDI, MRSA showed reduced adhesion to host cells and a 70% reduction in the GFP signal from intracellular bacteria. Additionally, light-activated Ga3+CHP significantly decreased the number of extracellular bacteria, reducing the potential for further infection. This study is the first to analyze aPDI toxicity in real time within an infection model, demonstrating that this method is neither cytotoxic nor phototoxic. |
| format | Article |
| id | doaj-art-504619703e8947dfa7998983a60ca3ff |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-504619703e8947dfa7998983a60ca3ff2025-01-12T12:24:15ZengNature PortfolioScientific Reports2045-23222025-01-0115111510.1038/s41598-024-84312-4Harnessing light-activated gallium porphyrins to combat intracellular Staphylococcus aureus using an in vitro keratinocyte infection modelKlaudia Szymczak0Michał Rychłowski1Lei Zhang2Joanna Nakonieczna3Laboratory of Photobiology and Molecular Diagnostics, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of GdanskLaboratory of Virus Molecular Biology, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of GdanskDepartment of Biochemical Engineering, School of Chemical Engineering and Technology, Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (MOE), Tianjin UniversityLaboratory of Photobiology and Molecular Diagnostics, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of GdanskAbstract Staphylococcus aureus (S. aureus) can survive inside nonprofessional phagocytes such as keratinocytes, enabling it to evade antibiotics and cause recurrent infections once treatment stops. New antibacterial strategies to eliminate intracellular, multidrug-resistant bacteria are needed. This study used a keratinocyte model infected with methicillin-resistant S. aureus (MRSA) to test light-activated compounds, specifically heme-mimetic gallium (III) porphyrin (Ga3+CHP) and visible light, known as antimicrobial photodynamic inactivation (aPDI), for eliminating intracellular MRSA. Ga3+CHP was found to accumulate more in infected cells, particularly within lysosomal structures where MRSA resides. Flow cytometry and fluorescence microscopy revealed significant colocalization of MRSA and Ga3+CHP. Under aPDI, MRSA showed reduced adhesion to host cells and a 70% reduction in the GFP signal from intracellular bacteria. Additionally, light-activated Ga3+CHP significantly decreased the number of extracellular bacteria, reducing the potential for further infection. This study is the first to analyze aPDI toxicity in real time within an infection model, demonstrating that this method is neither cytotoxic nor phototoxic.https://doi.org/10.1038/s41598-024-84312-4 |
| spellingShingle | Klaudia Szymczak Michał Rychłowski Lei Zhang Joanna Nakonieczna Harnessing light-activated gallium porphyrins to combat intracellular Staphylococcus aureus using an in vitro keratinocyte infection model Scientific Reports |
| title | Harnessing light-activated gallium porphyrins to combat intracellular Staphylococcus aureus using an in vitro keratinocyte infection model |
| title_full | Harnessing light-activated gallium porphyrins to combat intracellular Staphylococcus aureus using an in vitro keratinocyte infection model |
| title_fullStr | Harnessing light-activated gallium porphyrins to combat intracellular Staphylococcus aureus using an in vitro keratinocyte infection model |
| title_full_unstemmed | Harnessing light-activated gallium porphyrins to combat intracellular Staphylococcus aureus using an in vitro keratinocyte infection model |
| title_short | Harnessing light-activated gallium porphyrins to combat intracellular Staphylococcus aureus using an in vitro keratinocyte infection model |
| title_sort | harnessing light activated gallium porphyrins to combat intracellular staphylococcus aureus using an in vitro keratinocyte infection model |
| url | https://doi.org/10.1038/s41598-024-84312-4 |
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