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Insights into Gene Transcriptional Regulation of Kayvirus Bacteriophages Obtained from Therapeutic Mixtures.

ABSTRACT: Bacteriophages (phages) of the genus Kayvirus of Staphylococcus aureus are promising agents for therapeutic applications. In this study, we isolated Kayvirus phages, SAM1 and SAM2, from the Fersisi commercial phage cocktail (George Eliava Institute, Tbilisi, Georgia), which exhibits high sequence homology with phage K (≥94%, BLASTn). We found that phages SAM1 and SAM2 infected 95% and 86% of 21 MRSA of differing sequence types (MLST, SCCmec type) obtained from the Irish National MRSA collection, respectively. We conducted differential transcriptomic analysis by RNA-Seq on phage SAM1 during host infection, showing differential expression of its genes at different points during host infection. This analysis also allowed the identification of potentially adverse outcomes in the application of these phages to target MRSA as therapy. The interaction of phage SAM1 on the host caused the upregulation of prophage genes. Additionally, phage infection was found to cause the slight upregulation of host genes implicated in virulence factors relating to hemolysins, immune evasion, and adhesion, but also the downregulation of genes associated with enterotoxins. The findings of this study give further insights into the biology of kayviruses and their use as therapeutics.

SUBMITTER: Arroyo-Moreno S

PROVIDER: S-EPMC8952766 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Insights into Gene Transcriptional Regulation of Kayvirus Bacteriophages Obtained from Therapeutic Mixtures.

Arroyo-Moreno Sara S Buttimer Colin C Bottacini Francesca F Chanishvili Nina N Ross Paul P Hill Colin C Coffey Aidan A

Viruses 20220317 3

Bacteriophages (phages) of the genus Kayvirus of Staphylococcus aureus are promising agents for therapeutic applications. In this study, we isolated Kayvirus phages, SAM1 and SAM2, from the Fersisi commercial phage cocktail (George Eliava Institute, Tbilisi, Georgia), which exhibits high sequence homology with phage K (≥94%, BLASTn). We found that phages SAM1 and SAM2 infected 95% and 86% of 21 MRSA of differing sequence types (MLST, SCCmec type) obtained from the Iri ...[more]

PMID: 35337034

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Project description: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.

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Insights into Gene Transcriptional Regulation of Kayvirus Bacteriophages Obtained from Therapeutic Mixtures.

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Insights into Gene Transcriptional Regulation of <i>Kayvirus</i> Bacteriophages Obtained from Therapeutic Mixtures.

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