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Phage co-infection: a missing link in deciphering phage co-evolutionary dynamics

Project description

Bacteriophage evolution driven by concurrent infection

Bacteriophages – or phages for short – are viruses that specifically infect and replicate within bacteria. Phages can exchange genetic material between them as well as recombine their genome with host DNA, which influences phage genome mosaicism and subsequent evolution. Funded by the European Research Council, the MULTIPHAGE project will employ omics technologies and experimental analyses of model systems in culture to advance the understanding of phage-phage and phage-host co-evolution. The working hypothesis is that phage evolution is also driven by the simultaneous infection of the bacterial host by multiple phages. Given the role of phages in horizontal gene transfer and bacterial population control, project findings have the potential to improve biotechnology and medicine applications.

Objective

Phage genomes represent an impressive mosaicism with different genomic regions having distinct evolutionary histories resulting from horizontal gene transfer. By initiating an estimated 10^25 bacterial infections globally every second, phages encounter and recombine with DNA of the host or of prophage origin, further adding to their genome mosaicism. Accumulating evidence, including from my work, suggest that the simultaneous infection of bacterial host by multiple phages (co-infection) could also be an important driver of phage genome evolution. However, methodological limitations have so far prevented rigorous testing of this hypothesis due to failure of studying phage co-infection in natural settings. MULTIPHAGE will overcome these limitations by developing a novel approach for precisely deciphering how phage co-infection governs the co-evolutionary dynamics of phage genomes by pursuing three objectives. First, my team will quantify the prevalence of phage co-infection by constructing phage-host infection networks. Then, we will decipher the co-evolutionary relations of phage genes with no detectable sequence homology, using the novel concept of clusters of orthologous structures (COSs) and reconstructing structural phylogeny. Finally, we will unearth phage-phage interaction and co-infection strategies in high resolution by taking advantage of cultured model systems containing multiple phages co-infecting a single bacterial host population. To achieve these objectives, we will combine integrated omics methods (metaHiC proximity ligation, long-read metagenomic sequencing, and single-cell amplified genomics), COSs and structural phylogeny with high-resolution experimental confirmation of co-infection strategies. With its ground-breaking approach, MULTIPHAGE will transform our view of phage-host co-evolution by uncovering how phage co-infection and broad host range modulate the complexity of the infection network, clarifying its enigmatic co-evolutionary dynamics.

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Host institution

SVERIGES LANTBRUKSUNIVERSITET
Net EU contribution
€ 1 499 401,00
Address
ALMAS ALLE 8
750 07 Uppsala
Sweden

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Region
Östra Sverige Östra Mellansverige Uppsala län
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 499 401,00

Beneficiaries (1)