The Influence of Bacteriophages on the Metabolic Condition of Human Fibroblasts in Light of the Safety of Phage Therapy in Staphylococcal Skin Infections
Phage therapy has been successfully used as an experimental therapy in the treatment of multidrug-resistant strains of <i>Staphylococcus aureus</i> (MDRSA)-caused skin infections and is seen as the most promising alternative to antibiotics. However, in recent years a number of reports in...
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/6/5961 |
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| author | Katarzyna Kosznik-Kwaśnicka Małgorzata Stasiłojć Grzegorz Stasiłojć Natalia Kaźmierczak Lidia Piechowicz |
| author_facet | Katarzyna Kosznik-Kwaśnicka Małgorzata Stasiłojć Grzegorz Stasiłojć Natalia Kaźmierczak Lidia Piechowicz |
| author_sort | Katarzyna Kosznik-Kwaśnicka |
| collection | DOAJ |
| description | Phage therapy has been successfully used as an experimental therapy in the treatment of multidrug-resistant strains of <i>Staphylococcus aureus</i> (MDRSA)-caused skin infections and is seen as the most promising alternative to antibiotics. However, in recent years a number of reports indicating that phages can interact with eukaryotic cells emerged. Therefore, there is a need to re-evaluate phage therapy in light of safety. It is important to analyze not only the cytotoxicity of phages alone but also the impact their lytic activity against bacteria may have on human cells. As progeny virions rupture the cell wall, lipoteichoic acids are released in high quantities. It has been shown that they act as inflammatory agents and their presence could lead to the worsening of the patient’s condition and influence their recovery. In our work, we have tested if the treatment of normal human fibroblasts with staphylococcal phages will influence the metabolic state of the cell and the integrity of cell membranes. We have also analyzed the effectiveness of bacteriophages in reducing the number of MDRSA attached to human fibroblasts and the influence of the lytic activity of phages on cell viability. We observed that, out of three tested anti-<i>Staphylococcal</i> phages—vB_SauM-A, vB_SauM-C and vB_SauM-D—high concentrations (10<sup>9</sup> PFU/mL) of two, vB_SauM-A and vB_SauM-D, showed a negative impact on the viability of human fibroblasts. However, a dose of 10<sup>7</sup> PFU/mL had no effect on the metabolic activity or membrane integrity of the cells. We also observed that the addition of phages alleviated the negative effect of the MDRSA infection on fibroblasts’ viability, as phages were able to effectively reduce the number of bacteria in the co-culture. We believe that these results will contribute to a better understanding of the influence of phage therapy on human cells and encourage even more studies on this topic. |
| first_indexed | 2024-03-11T06:24:10Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:24:10Z |
| publishDate | 2023-03-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-882126e1ec634fcf8fa8c8b755a971322023-11-17T11:41:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246596110.3390/ijms24065961The Influence of Bacteriophages on the Metabolic Condition of Human Fibroblasts in Light of the Safety of Phage Therapy in Staphylococcal Skin InfectionsKatarzyna Kosznik-Kwaśnicka0Małgorzata Stasiłojć1Grzegorz Stasiłojć2Natalia Kaźmierczak3Lidia Piechowicz4Department of Medical Microbiology, Faculty of Medicine, Medical University of Gdańsk, Dębowa 25, 80-204 Gdansk, PolandDepartment of Cell Biology and Immunology, Intercollegiate Faculty of Biotechnology of University of Gdańsk and Medical University of Gdańsk, Dębinki 1, 80-211 Gdańsk, PolandDepartment of Cell Biology and Immunology, Intercollegiate Faculty of Biotechnology of University of Gdańsk and Medical University of Gdańsk, Dębinki 1, 80-211 Gdańsk, PolandDepartment of Medical Microbiology, Faculty of Medicine, Medical University of Gdańsk, Dębowa 25, 80-204 Gdansk, PolandDepartment of Medical Microbiology, Faculty of Medicine, Medical University of Gdańsk, Dębowa 25, 80-204 Gdansk, PolandPhage therapy has been successfully used as an experimental therapy in the treatment of multidrug-resistant strains of <i>Staphylococcus aureus</i> (MDRSA)-caused skin infections and is seen as the most promising alternative to antibiotics. However, in recent years a number of reports indicating that phages can interact with eukaryotic cells emerged. Therefore, there is a need to re-evaluate phage therapy in light of safety. It is important to analyze not only the cytotoxicity of phages alone but also the impact their lytic activity against bacteria may have on human cells. As progeny virions rupture the cell wall, lipoteichoic acids are released in high quantities. It has been shown that they act as inflammatory agents and their presence could lead to the worsening of the patient’s condition and influence their recovery. In our work, we have tested if the treatment of normal human fibroblasts with staphylococcal phages will influence the metabolic state of the cell and the integrity of cell membranes. We have also analyzed the effectiveness of bacteriophages in reducing the number of MDRSA attached to human fibroblasts and the influence of the lytic activity of phages on cell viability. We observed that, out of three tested anti-<i>Staphylococcal</i> phages—vB_SauM-A, vB_SauM-C and vB_SauM-D—high concentrations (10<sup>9</sup> PFU/mL) of two, vB_SauM-A and vB_SauM-D, showed a negative impact on the viability of human fibroblasts. However, a dose of 10<sup>7</sup> PFU/mL had no effect on the metabolic activity or membrane integrity of the cells. We also observed that the addition of phages alleviated the negative effect of the MDRSA infection on fibroblasts’ viability, as phages were able to effectively reduce the number of bacteria in the co-culture. We believe that these results will contribute to a better understanding of the influence of phage therapy on human cells and encourage even more studies on this topic.https://www.mdpi.com/1422-0067/24/6/5961phage therapyMDRSAMRSA<i>Staphylococcus aureus</i>bacteriophagesfibroblasts |
| spellingShingle | Katarzyna Kosznik-Kwaśnicka Małgorzata Stasiłojć Grzegorz Stasiłojć Natalia Kaźmierczak Lidia Piechowicz The Influence of Bacteriophages on the Metabolic Condition of Human Fibroblasts in Light of the Safety of Phage Therapy in Staphylococcal Skin Infections International Journal of Molecular Sciences phage therapy MDRSA MRSA <i>Staphylococcus aureus</i> bacteriophages fibroblasts |
| title | The Influence of Bacteriophages on the Metabolic Condition of Human Fibroblasts in Light of the Safety of Phage Therapy in Staphylococcal Skin Infections |
| title_full | The Influence of Bacteriophages on the Metabolic Condition of Human Fibroblasts in Light of the Safety of Phage Therapy in Staphylococcal Skin Infections |
| title_fullStr | The Influence of Bacteriophages on the Metabolic Condition of Human Fibroblasts in Light of the Safety of Phage Therapy in Staphylococcal Skin Infections |
| title_full_unstemmed | The Influence of Bacteriophages on the Metabolic Condition of Human Fibroblasts in Light of the Safety of Phage Therapy in Staphylococcal Skin Infections |
| title_short | The Influence of Bacteriophages on the Metabolic Condition of Human Fibroblasts in Light of the Safety of Phage Therapy in Staphylococcal Skin Infections |
| title_sort | influence of bacteriophages on the metabolic condition of human fibroblasts in light of the safety of phage therapy in staphylococcal skin infections |
| topic | phage therapy MDRSA MRSA <i>Staphylococcus aureus</i> bacteriophages fibroblasts |
| url | https://www.mdpi.com/1422-0067/24/6/5961 |
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