Next-Generation '-omics' Approaches Reveal a Massive Alteration of Host RNA Metabolism during Bacteriophage Infection of Pseudomonas aeruginosa
| Autor: | Peter Jorth, Marc Monot, Michael B. Zimmermann, Uwe Sauer, Maria Kogadeeva, Jeroen De Smet, Anne Chevallereau, Marvin Whiteley, Rob Lavigne, Bob G. Blasdel, Laurent Debarbieux |
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| Přispěvatelé: | Biologie Moléculaire du Gène chez les Extrêmophiles (BMGE), Institut Pasteur [Paris], Cellule Pasteur, PRES Sorbonne Paris Cité-Université Paris Diderot - Paris 7 (UPD7), Laboratory of Gene Technology, Department of Biosystems, KU Leuven, Pathogénèse des Bactéries Anaérobies / Pathogenesis of Bacterial Anaerobes (PBA (U-Pasteur_6)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7), Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, Center for Infectious Disease, University of Texas at Austin [Austin], This research was supported by the Geconcerteerde Onderzoeks Actie grant ‘Phage Biosystems’ from the KULeuven (http://www.kuleuven.be/onderzoek/kernprojecten/goa.htm). BGB has a PhD scholarship within the framework of an Onderzoeks Toelage grant of the KULeuven. AC was supported by PhD fellowships from the Ministère de l’Enseignement Supérieur et de la Recherche, ED N°516 B3MI Paris Diderot University (http://www.enseignementsup-recherche.gouv.fr/)., Ansaldi, Mireille, Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Institut Pasteur [Paris] (IP), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Bacterial Diseases Cancer Research Operon Gene Expression Pathogenesis medicine.disease_cause Pathology and Laboratory Medicine Biochemistry Bacteriophage Gene expression Medicine and Health Sciences Bacteriophages Genetics (clinical) Antisense RNA biology High-Throughput Nucleotide Sequencing Pseudomonas Aeruginosa 3. Good health Bacterial Pathogens Nucleic acids Infectious Diseases Medical Microbiology Pyrimidine metabolism Viruses Host-Pathogen Interactions RNA Viral Metabolic Pathways Pathogens Research Article Gene Expression Regulation Viral lcsh:QH426-470 Virulence Genomics Microbiology Virus Effects on Host Gene Expression 03 medical and health sciences Virology Pseudomonas medicine Genetics Metabolomics Pseudomonas Infections Molecular Biology Escherichia coli Microbial Pathogens Ecology Evolution Behavior and Systematics Bacteria Organisms Biology and Life Sciences Gene Expression Regulation Bacterial biology.organism_classification [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology lcsh:Genetics 030104 developmental biology Metabolism RNA |
| Zdroj: | PLoS Genetics PLoS Genetics, Public Library of Science, 2016, 12 (7), pp.e1006134. ⟨10.1371/journal.pgen.1006134⟩ PLoS Genetics, Vol 12, Iss 7, p e1006134 (2016) PLoS Genetics, 12 (7) PLoS Genetics, 2016, 12 (7), pp.e1006134. ⟨10.1371/journal.pgen.1006134⟩ |
| ISSN: | 1553-7390 1553-7404 |
| DOI: | 10.1371/journal.pgen.1006134⟩ |
| Popis: | As interest in the therapeutic and biotechnological potentials of bacteriophages has grown, so has value in understanding their basic biology. However, detailed knowledge of infection cycles has been limited to a small number of model bacteriophages, mostly infecting Escherichia coli. We present here the first analysis coupling data obtained from global next-generation approaches, RNA-Sequencing and metabolomics, to characterize interactions between the virulent bacteriophage PAK_P3 and its host Pseudomonas aeruginosa. We detected a dramatic global depletion of bacterial transcripts coupled with their replacement by viral RNAs over the course of infection, eventually leading to drastic changes in pyrimidine metabolism. This process relies on host machinery hijacking as suggested by the strong up-regulation of one bacterial operon involved in RNA processing. Moreover, we found that RNA-based regulation plays a central role in PAK_P3 lifecycle as antisense transcripts are produced mainly during the early stage of infection and viral small non coding RNAs are massively expressed at the end of infection. This work highlights the prominent role of RNA metabolism in the infection strategy of a bacteriophage belonging to a new characterized sub-family of viruses with promising therapeutic potential. Author Summary The increase of the proportion of multidrug resistant bacterial strains is alarming and alternative ways to treat infections are necessary such as the use of the natural enemies of bacteria, also known as phage therapy. However, explorations of the molecular mechanisms underlying the viral cycle of bacteriophages have been so far restricted to a small number of viruses infecting model bacteria such as Escherichia coli. By combining next-generation transcriptomics and metabolomics approaches, we have now demonstrated that the virulent bacteriophage PAK_P3, infecting the opportunistic pathogen Pseudomonas aeruginosa, directly interferes with specific host metabolic pathways to complete its infection cycle. In particular, it triggers a dramatic degradation of host RNAs and stimulates bacterial pyrimidine metabolism to promote a nucleotide turnover. Overall, we found that upon PAK_P3 infection, host metabolism is redirected to generate the required building blocks for efficient viral replication. We also showed that PAK_P3 gene expression relies on RNA-based regulation strategies using small non coding RNAs and antisense RNAs. Our findings highlight the molecular strategies employed by this virulent phage, which is a representative of a new subfamily of viruses shown to display promising therapeutic values. |
| Databáze: | OpenAIRE |
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