title: Next-Generation "-omics" Approaches Reveal a Massive Alteration of Host RNA Metabolism during Bacteriophage Infection of Pseudomonas aeruginosa.
abstract: 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.
authors.affiliation: Institut Pasteur, Molecular Biology of the Gene in Extremophiles Unit, Department of Microbiology, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Chevallereau
authors.affiliation: Laboratory of Gene Technology, Department of Biosystems, KU Leuven, Leuven, Belgium.
authors.forename: Bob G
authors.initials: BG
authors.lastname: Blasdel
authors.affiliation: Laboratory of Gene Technology, Department of Biosystems, KU Leuven, Leuven, Belgium.
authors.forename: Jeroen
authors.identifier: 0000-0002-7200-089X
authors.initials: J
authors.lastname: De Smet
authors.affiliation: Institut Pasteur, Laboratoire Pathogenèse des bactéries anaérobies, Département de Microbiologie, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Monot
authors.affiliation: Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule (ETH) Zürich, Zürich, Switzerland.
authors.forename: Michael
authors.identifier: 0000-0002-5797-3589
authors.initials: M
authors.lastname: Zimmermann
authors.affiliation: Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule (ETH) Zürich, Zürich, Switzerland.
authors.forename: Maria
authors.initials: M
authors.lastname: Kogadeeva
authors.affiliation: Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule (ETH) Zürich, Zürich, Switzerland.
authors.forename: Uwe
authors.initials: U
authors.lastname: Sauer
authors.affiliation: Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, Center for Infectious Disease, University of Texas, Austin, Texas, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Jorth
authors.affiliation: Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, Center for Infectious Disease, University of Texas, Austin, Texas, United States of America.
authors.forename: Marvin
authors.initials: M
authors.lastname: Whiteley
authors.affiliation: Institut Pasteur, Molecular Biology of the Gene in Extremophiles Unit, Department of Microbiology, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Debarbieux
authors.affiliation: Laboratory of Gene Technology, Department of Biosystems, KU Leuven, Leuven, Belgium.
authors.forename: Rob
authors.initials: R
authors.lastname: Lavigne
mesh_terms: D001435:Bacteriophages / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D015967:Gene Expression Regulation, Viral; D059014:High-Throughput Nucleotide Sequencing; D055432:Metabolomics; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism
chemical_list: D012367:RNA, Viral