Bacteriophage self-counting in the presence of viral replication

Tianyou Yao, Seth Coleman, Thu Vu Phuc Nguyen, Ido Golding, Oleg A. Igoshin

Research output: Contribution to journalArticlepeer-review


When host cells are in low abundance, temperate bacteriophages opt for dormant (lysogenic) infection. Phage lambda implements this strategy by increasing the frequency of lysogeny at higher multiplicity of infection (MOI). However, it remains unclear how the phage reliably counts infecting viral genomes even as their intracellular number increases because of replication. By combining theoretical modeling with single-cell measurements of viral copy number and gene expression, we find that instead of hindering lambda’s decision, replication facilitates it. In a nonreplicating mutant, viral gene expression simply scales with MOI rather than diverging into lytic (virulent) and lysogenic trajectories. A similar pattern is followed during early infection by wild-type phage. However, later in the infection, the modulation of viral replication by the decision genes amplifies the initially modest gene expression differences into divergent trajectories. Replication thus ensures the optimal decision—lysis upon single-phage infection and lysogeny at higher MOI.

Original languageEnglish (US)
Article numbere2104163118
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number51
StatePublished - Dec 21 2021


  • Bacteriophage
  • Cell-fate decision
  • E. coli
  • Mathematical modeling
  • Single cell

ASJC Scopus subject areas

  • General


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