Response of Staphylococcus aureus to combination of virulent bacteriophage vB_SauM-515A1 and linezolid
The combined use of lytic bacteriophages with antibiotics is currently being explored as a strategy to enhance the effectiveness of infectious disease therapies, including those caused by Staphylococcus aureus. In this study, we investigated the synergistic potential of bacteriophage vB_SauM-515A1 (...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1519312/full |
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| author | Narina K. Abdraimova Egor A. Shitikov Dmitry A. Bespiatykh Roman B. Gorodnichev Ksenia M. Klimina Vladimir A. Veselovsky Daria I. Boldyreva Alexandra S. Bogdanova Alexandra S. Bogdanova Dmitry V. Klinov Dmitry V. Klinov Maria A. Kornienko |
| author_facet | Narina K. Abdraimova Egor A. Shitikov Dmitry A. Bespiatykh Roman B. Gorodnichev Ksenia M. Klimina Vladimir A. Veselovsky Daria I. Boldyreva Alexandra S. Bogdanova Alexandra S. Bogdanova Dmitry V. Klinov Dmitry V. Klinov Maria A. Kornienko |
| author_sort | Narina K. Abdraimova |
| collection | DOAJ |
| description | The combined use of lytic bacteriophages with antibiotics is currently being explored as a strategy to enhance the effectiveness of infectious disease therapies, including those caused by Staphylococcus aureus. In this study, we investigated the synergistic potential of bacteriophage vB_SauM-515A1 (Herelleviridae family) and the first-line antibiotic linezolid against the methicillin-resistant S. aureus strain SA0413Rev. A checkerboard assay revealed a significant synergistic effect against planktonic cells (FIC = 0.225): a combination of 1/8 MIC of linezolid and 0.01 MOI of the bacteriophage completely inhibited bacterial growth. However, the impact on biofilm-associated cells depended on the treatment sequence. Sequential administration resulted in antagonism, while simultaneous application demonstrated a synergistic effect, as confirmed through scanning electron microscopy. Transcriptomic analysis of S. aureus SA0413Rev under the combined influence of linezolid (1/4 MIC) and bacteriophage vB_SauM-515A1 (10 MOI) predominantly reflected changes associated with productive bacteriophage infection, including alterations in nucleotide metabolism, activation of prophage regions, and virulence factors. Furthermore, both agents affected energy and carbon metabolism. These findings contribute to the development of combination therapy approaches for infections caused by S. aureus and highlight the importance of optimizing treatment conditions for maximal therapeutic efficacy. |
| format | Article |
| id | doaj-art-b9b16cec0c1446a0b3cf8a5af679b724 |
| institution | OA Journals |
| issn | 1664-302X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj-art-b9b16cec0c1446a0b3cf8a5af679b7242025-08-20T01:58:35ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2024-12-011510.3389/fmicb.2024.15193121519312Response of Staphylococcus aureus to combination of virulent bacteriophage vB_SauM-515A1 and linezolidNarina K. Abdraimova0Egor A. Shitikov1Dmitry A. Bespiatykh2Roman B. Gorodnichev3Ksenia M. Klimina4Vladimir A. Veselovsky5Daria I. Boldyreva6Alexandra S. Bogdanova7Alexandra S. Bogdanova8Dmitry V. Klinov9Dmitry V. Klinov10Maria A. Kornienko11Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, RussiaLopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, RussiaLopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, RussiaLopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, RussiaLopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, RussiaLopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, RussiaLopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, RussiaLopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, RussiaMoscow Institute of Physics and Technology, National Research University, Dolgoprudny, RussiaLopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, RussiaMoscow Institute of Physics and Technology, National Research University, Dolgoprudny, RussiaLopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, RussiaThe combined use of lytic bacteriophages with antibiotics is currently being explored as a strategy to enhance the effectiveness of infectious disease therapies, including those caused by Staphylococcus aureus. In this study, we investigated the synergistic potential of bacteriophage vB_SauM-515A1 (Herelleviridae family) and the first-line antibiotic linezolid against the methicillin-resistant S. aureus strain SA0413Rev. A checkerboard assay revealed a significant synergistic effect against planktonic cells (FIC = 0.225): a combination of 1/8 MIC of linezolid and 0.01 MOI of the bacteriophage completely inhibited bacterial growth. However, the impact on biofilm-associated cells depended on the treatment sequence. Sequential administration resulted in antagonism, while simultaneous application demonstrated a synergistic effect, as confirmed through scanning electron microscopy. Transcriptomic analysis of S. aureus SA0413Rev under the combined influence of linezolid (1/4 MIC) and bacteriophage vB_SauM-515A1 (10 MOI) predominantly reflected changes associated with productive bacteriophage infection, including alterations in nucleotide metabolism, activation of prophage regions, and virulence factors. Furthermore, both agents affected energy and carbon metabolism. These findings contribute to the development of combination therapy approaches for infections caused by S. aureus and highlight the importance of optimizing treatment conditions for maximal therapeutic efficacy.https://www.frontiersin.org/articles/10.3389/fmicb.2024.1519312/fullbacteriophageStaphylococcus aureuslinezolidcombination therapybiofilm |
| spellingShingle | Narina K. Abdraimova Egor A. Shitikov Dmitry A. Bespiatykh Roman B. Gorodnichev Ksenia M. Klimina Vladimir A. Veselovsky Daria I. Boldyreva Alexandra S. Bogdanova Alexandra S. Bogdanova Dmitry V. Klinov Dmitry V. Klinov Maria A. Kornienko Response of Staphylococcus aureus to combination of virulent bacteriophage vB_SauM-515A1 and linezolid Frontiers in Microbiology bacteriophage Staphylococcus aureus linezolid combination therapy biofilm |
| title | Response of Staphylococcus aureus to combination of virulent bacteriophage vB_SauM-515A1 and linezolid |
| title_full | Response of Staphylococcus aureus to combination of virulent bacteriophage vB_SauM-515A1 and linezolid |
| title_fullStr | Response of Staphylococcus aureus to combination of virulent bacteriophage vB_SauM-515A1 and linezolid |
| title_full_unstemmed | Response of Staphylococcus aureus to combination of virulent bacteriophage vB_SauM-515A1 and linezolid |
| title_short | Response of Staphylococcus aureus to combination of virulent bacteriophage vB_SauM-515A1 and linezolid |
| title_sort | response of staphylococcus aureus to combination of virulent bacteriophage vb saum 515a1 and linezolid |
| topic | bacteriophage Staphylococcus aureus linezolid combination therapy biofilm |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2024.1519312/full |
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