Global Transcriptomic Analysis of Bacteriophage-Host Interactions between a Kayvirus Therapeutic Phage and Staphylococcus aureus
ABSTRACT Kayviruses are polyvalent broad host range staphylococcal phages with a potential to combat staphylococcal infections. However, the implementation of rational phage therapy in medicine requires a thorough understanding of the interactions between bacteriophages and pathogens at omics level....
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-06-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.00123-22 |
| _version_ | 1818255490254110720 |
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| author | Adéla Finstrlová Ivana Mašlaňová Bob G. Blasdel Reuter Jiří Doškař Friedrich Götz Roman Pantůček |
| author_facet | Adéla Finstrlová Ivana Mašlaňová Bob G. Blasdel Reuter Jiří Doškař Friedrich Götz Roman Pantůček |
| author_sort | Adéla Finstrlová |
| collection | DOAJ |
| description | ABSTRACT Kayviruses are polyvalent broad host range staphylococcal phages with a potential to combat staphylococcal infections. However, the implementation of rational phage therapy in medicine requires a thorough understanding of the interactions between bacteriophages and pathogens at omics level. To evaluate the effect of a phage used in therapy on its host bacterium, we performed differential transcriptomic analysis by RNA-Seq from bacteriophage K of genus Kayvirus infecting two Staphylococcus aureus strains, prophage-less strain SH1000 and quadruple lysogenic strain Newman. The temporal transcriptional profile of phage K was comparable in both strains except for a few loci encoding hypothetical proteins. Stranded sequencing revealed transcription of phage noncoding RNAs that may play a role in the regulation of phage and host gene expression. The transcriptional response of S. aureus to phage K infection resembles a general stress response with differential expression of genes involved in a DNA damage response. The host transcriptional changes involved upregulation of nucleotide, amino acid and energy synthesis and transporter genes and downregulation of host transcription factors. The interaction of phage K with variable genetic elements of the host showed slight upregulation of gene expression of prophage integrases and antirepressors. The virulence genes involved in adhesion and immune evasion were only marginally affected, making phage K suitable for therapy. IMPORTANCE Bacterium Staphylococcus aureus is a common human and veterinary pathogen that causes mild to life-threatening infections. As strains of S. aureus are becoming increasingly resistant to multiple antibiotics, the need to search for new therapeutics is urgent. A promising alternative to antibiotic treatment of staphylococcal infections is a phage therapy using lytic phages from the genus Kayvirus. Here, we present a comprehensive view on the phage-bacterium interactions on transcriptomic level that improves the knowledge of molecular mechanisms underlying the Kayvirus lytic action. The results will ensure safer usage of the phage therapeutics and may also serve as a basis for the development of new antibacterial strategies. |
| first_indexed | 2024-12-12T17:12:41Z |
| format | Article |
| id | doaj.art-86ae0a436d7e42038659bf7c92690dbd |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-12-12T17:12:41Z |
| publishDate | 2022-06-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-86ae0a436d7e42038659bf7c92690dbd2022-12-22T00:17:51ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-06-0110310.1128/spectrum.00123-22Global Transcriptomic Analysis of Bacteriophage-Host Interactions between a Kayvirus Therapeutic Phage and Staphylococcus aureusAdéla Finstrlová0Ivana Mašlaňová1Bob G. Blasdel Reuter2Jiří Doškař3Friedrich Götz4Roman Pantůček5Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech RepublicDepartment of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech RepublicVésale Bioscience, Vésale Pharma, Noville sur Mehaigne, BelgiumDepartment of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech RepublicMicrobial Genetics, Interfaculty Institute of Microbiology and Infection Medicine Tübingen, University of Tübingen, Tübingen, GermanyDepartment of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech RepublicABSTRACT Kayviruses are polyvalent broad host range staphylococcal phages with a potential to combat staphylococcal infections. However, the implementation of rational phage therapy in medicine requires a thorough understanding of the interactions between bacteriophages and pathogens at omics level. To evaluate the effect of a phage used in therapy on its host bacterium, we performed differential transcriptomic analysis by RNA-Seq from bacteriophage K of genus Kayvirus infecting two Staphylococcus aureus strains, prophage-less strain SH1000 and quadruple lysogenic strain Newman. The temporal transcriptional profile of phage K was comparable in both strains except for a few loci encoding hypothetical proteins. Stranded sequencing revealed transcription of phage noncoding RNAs that may play a role in the regulation of phage and host gene expression. The transcriptional response of S. aureus to phage K infection resembles a general stress response with differential expression of genes involved in a DNA damage response. The host transcriptional changes involved upregulation of nucleotide, amino acid and energy synthesis and transporter genes and downregulation of host transcription factors. The interaction of phage K with variable genetic elements of the host showed slight upregulation of gene expression of prophage integrases and antirepressors. The virulence genes involved in adhesion and immune evasion were only marginally affected, making phage K suitable for therapy. IMPORTANCE Bacterium Staphylococcus aureus is a common human and veterinary pathogen that causes mild to life-threatening infections. As strains of S. aureus are becoming increasingly resistant to multiple antibiotics, the need to search for new therapeutics is urgent. A promising alternative to antibiotic treatment of staphylococcal infections is a phage therapy using lytic phages from the genus Kayvirus. Here, we present a comprehensive view on the phage-bacterium interactions on transcriptomic level that improves the knowledge of molecular mechanisms underlying the Kayvirus lytic action. The results will ensure safer usage of the phage therapeutics and may also serve as a basis for the development of new antibacterial strategies.https://journals.asm.org/doi/10.1128/spectrum.00123-22phage-host interactionsStaphylococcus phagesKayvirusRNA-Seqviral transcriptionnoncoding RNA |
| spellingShingle | Adéla Finstrlová Ivana Mašlaňová Bob G. Blasdel Reuter Jiří Doškař Friedrich Götz Roman Pantůček Global Transcriptomic Analysis of Bacteriophage-Host Interactions between a Kayvirus Therapeutic Phage and Staphylococcus aureus Microbiology Spectrum phage-host interactions Staphylococcus phages Kayvirus RNA-Seq viral transcription noncoding RNA |
| title | Global Transcriptomic Analysis of Bacteriophage-Host Interactions between a Kayvirus Therapeutic Phage and Staphylococcus aureus |
| title_full | Global Transcriptomic Analysis of Bacteriophage-Host Interactions between a Kayvirus Therapeutic Phage and Staphylococcus aureus |
| title_fullStr | Global Transcriptomic Analysis of Bacteriophage-Host Interactions between a Kayvirus Therapeutic Phage and Staphylococcus aureus |
| title_full_unstemmed | Global Transcriptomic Analysis of Bacteriophage-Host Interactions between a Kayvirus Therapeutic Phage and Staphylococcus aureus |
| title_short | Global Transcriptomic Analysis of Bacteriophage-Host Interactions between a Kayvirus Therapeutic Phage and Staphylococcus aureus |
| title_sort | global transcriptomic analysis of bacteriophage host interactions between a kayvirus therapeutic phage and staphylococcus aureus |
| topic | phage-host interactions Staphylococcus phages Kayvirus RNA-Seq viral transcription noncoding RNA |
| url | https://journals.asm.org/doi/10.1128/spectrum.00123-22 |
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