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.

Low-level predation by lytic phage phiIPLA-RODI promotes biofilm formation and triggers the stringent response in Staphylococcus aureus

“…on E. coli describes the upregulation of spoT at 30 minutes post infection with phage PRD1. Additionally, a recent study using a metabolomics approach detected that changes in the levels of (p)ppGpp were fairly common in the infection of P. aeruginosa with different phages51. This clearly suggests that albeit the stringent response is not always present upon phage infection, it is fairly widespread in different microbe-phage systems.…”

Bacterial cell‐to‐cell signaling promotes the evolution of resistance to parasitic bacteriophages

“…(2013) and De Smet et al. (2016) used lytic phages belonging to a family Myoviridae . A recently published paper has also demonstrated that lysogenic phages can turn a susceptible E. coli strain resistant to a lytic phage via CRISPR‐Cas system modification (Yosef, Manor, Kiro, & Qimron, 2015).…”

Identification of Essential Genes in the Salmonella Phage SPN3US Reveals Novel Insights into Giant Phage Head Structure and Assembly

“…One approach to understanding phage infections is to use omics approaches, including transcriptomics and metabolomics (26, 27); however, seeing a clear link between any individual phage gene and its functions is not always straightforward. Historically, the genetic system based on the T4 phage has been one of the most paradigm-shifting model systems in biology, and it is critical for our understanding of the fine structure of the gene and many of the founding principles of molecular genetics (28–31).…”