title: High coverage metabolomics analysis reveals phage-specific alterations to Pseudomonas aeruginosa physiology during infection.
abstract: Phage-mediated metabolic changes in bacteria are hypothesized to markedly alter global nutrient and biogeochemical cycles. Despite their theoretic importance, experimental data on the net metabolic impact of phage infection on the bacterial metabolism remains scarce. In this study, we tracked the dynamics of intracellular metabolites using untargeted high coverage metabolomics in Pseudomonas aeruginosa cells infected with lytic bacteriophages from six distinct phage genera. Analysis of the metabolomics data indicates an active interference in the host metabolism. In general, phages elicit an increase in pyrimidine and nucleotide sugar metabolism. Furthermore, clear phage-specific and infection stage-specific responses are observed, ranging from extreme metabolite depletion (for example, phage YuA) to complete reorganization of the metabolism (for example, phage phiKZ). As expected, pathways targeted by the phage-encoded auxiliary metabolic genes (AMGs) were enriched among the metabolites changing during infection. The effect on pyrimidine metabolism of phages encoding AMGs capable of host genome degradation (for example, YuA and LUZ19) was distinct from those lacking nuclease-encoding genes (for example, phiKZ), which demonstrates the link between the encoded set of AMGs of a phage and its impact on host physiology. However, a large fraction of the profound effect on host metabolism could not be attributed to the phage-encoded AMGs. We suggest a potentially crucial role for small, 'non-enzymatic' peptides in metabolism take-over and hypothesize on potential biotechnical applications for such peptides. The highly phage-specific nature of the metabolic impact emphasizes the potential importance of the 'phage diversity' parameter when studying metabolic interactions in complex communities.
authors.affiliation: Laboratory of Gene Technology, Department of Biosystems, KU Leuven, Heverlee, Belgium.
authors.forename: Jeroen
authors.initials: J
authors.lastname: De Smet
authors.affiliation: Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule (ETH) Zürich, Zürich, Switzerland.
authors.forename: Michael
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: Laboratory of Gene Technology, Department of Biosystems, KU Leuven, Heverlee, Belgium.|Unit Bacterial Diseases, Scientific Institute of Public Health (WIV-ISP), Brussels, Belgium.
authors.forename: Pieter-Jan
authors.initials: PJ
authors.lastname: Ceyssens
authors.affiliation: Laboratory of Gene Technology, Department of Biosystems, KU Leuven, Heverlee, Belgium.
authors.forename: Wesley
authors.initials: W
authors.lastname: Vermaelen
authors.affiliation: Laboratory of Gene Technology, Department of Biosystems, KU Leuven, Heverlee, Belgium.
authors.forename: Bob
authors.initials: B
authors.lastname: Blasdel
authors.affiliation: Laboratory of Gene Technology, Department of Biosystems, KU Leuven, Heverlee, Belgium.
authors.forename: Ho
authors.initials: H
authors.lastname: Bin Jang
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: Laboratory of Gene Technology, Department of Biosystems, KU Leuven, Heverlee, Belgium.
authors.forename: Rob
authors.initials: R
authors.lastname: Lavigne
mesh_terms: D016679:Genome, Viral / Q000235:genetics*; D055432:Metabolomics; D017900:Myoviridae / Q000235:genetics; D017105:Pseudomonas Phages / Q000235:genetics / Q000502:physiology*; D011550:Pseudomonas aeruginosa / Q000502:physiology / Q000821:virology*