Phage activity against Staphylococcus aureus is impaired in plasma and synovial fluid
Abstract S. aureus is a pathogen that frequently causes severe morbidity and phage therapy is being discussed as an alternative to antibiotics for the treatment of S. aureus infections. In this in vitro and animal study, we demonstrated that the activity of anti-staphylococcal phages is severely imp...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-10-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-45405-8 |
| _version_ | 1797560206870183936 |
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| author | Michele Mutti David Sáez Moreno Marcela Restrepo-Córdoba Zehra Visram Grégory Resch Lorenzo Corsini |
| author_facet | Michele Mutti David Sáez Moreno Marcela Restrepo-Córdoba Zehra Visram Grégory Resch Lorenzo Corsini |
| author_sort | Michele Mutti |
| collection | DOAJ |
| description | Abstract S. aureus is a pathogen that frequently causes severe morbidity and phage therapy is being discussed as an alternative to antibiotics for the treatment of S. aureus infections. In this in vitro and animal study, we demonstrated that the activity of anti-staphylococcal phages is severely impaired in 0.5% plasma or synovial fluid. Despite phage replication in these matrices, lysis of the bacteria was slower than phage propagation, and no reduction of the bacterial population was observed. The inhibition of the phages associated with a reduction in phage adsorption, quantified to 99% at 10% plasma. S. aureus is known to bind multiple coagulation factors, resulting in the formation of aggregates and blood clots that might protect the bacterium from the phages. Here, we show that purified fibrinogen at a sub-physiological concentration of 0.4 mg/ml is sufficient to impair phage activity. In contrast, dissolution of the clots by tissue plasminogen activator (tPA) partially restored phage activity. Consistent with these in vitro findings, phage treatment did not reduce bacterial burdens in a neutropenic mouse S. aureus thigh infection model. In summary, phage treatment of S. aureus infections inside the body may be fundamentally challenging, and more investigation is needed prior to proceeding to in-human trials. |
| first_indexed | 2024-03-10T17:56:06Z |
| format | Article |
| id | doaj.art-8a7f31bf756e47c59dbe719d3c4cf9a9 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T17:56:06Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-8a7f31bf756e47c59dbe719d3c4cf9a92023-11-20T09:10:52ZengNature PortfolioScientific Reports2045-23222023-10-0113111310.1038/s41598-023-45405-8Phage activity against Staphylococcus aureus is impaired in plasma and synovial fluidMichele Mutti0David Sáez Moreno1Marcela Restrepo-Córdoba2Zehra Visram3Grégory Resch4Lorenzo Corsini5BioNTech R&D Austria GmbHBioNTech R&D Austria GmbHBioNTech R&D Austria GmbHBioNTech R&D Austria GmbHCenter for Research and Innovation in Clinical Pharmaceutical Sciences (CRISP), Lausanne Hospital (CHUV)BioNTech R&D Austria GmbHAbstract S. aureus is a pathogen that frequently causes severe morbidity and phage therapy is being discussed as an alternative to antibiotics for the treatment of S. aureus infections. In this in vitro and animal study, we demonstrated that the activity of anti-staphylococcal phages is severely impaired in 0.5% plasma or synovial fluid. Despite phage replication in these matrices, lysis of the bacteria was slower than phage propagation, and no reduction of the bacterial population was observed. The inhibition of the phages associated with a reduction in phage adsorption, quantified to 99% at 10% plasma. S. aureus is known to bind multiple coagulation factors, resulting in the formation of aggregates and blood clots that might protect the bacterium from the phages. Here, we show that purified fibrinogen at a sub-physiological concentration of 0.4 mg/ml is sufficient to impair phage activity. In contrast, dissolution of the clots by tissue plasminogen activator (tPA) partially restored phage activity. Consistent with these in vitro findings, phage treatment did not reduce bacterial burdens in a neutropenic mouse S. aureus thigh infection model. In summary, phage treatment of S. aureus infections inside the body may be fundamentally challenging, and more investigation is needed prior to proceeding to in-human trials.https://doi.org/10.1038/s41598-023-45405-8 |
| spellingShingle | Michele Mutti David Sáez Moreno Marcela Restrepo-Córdoba Zehra Visram Grégory Resch Lorenzo Corsini Phage activity against Staphylococcus aureus is impaired in plasma and synovial fluid Scientific Reports |
| title | Phage activity against Staphylococcus aureus is impaired in plasma and synovial fluid |
| title_full | Phage activity against Staphylococcus aureus is impaired in plasma and synovial fluid |
| title_fullStr | Phage activity against Staphylococcus aureus is impaired in plasma and synovial fluid |
| title_full_unstemmed | Phage activity against Staphylococcus aureus is impaired in plasma and synovial fluid |
| title_short | Phage activity against Staphylococcus aureus is impaired in plasma and synovial fluid |
| title_sort | phage activity against staphylococcus aureus is impaired in plasma and synovial fluid |
| url | https://doi.org/10.1038/s41598-023-45405-8 |
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