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Phage Phenomics: Physiological Approaches to Characterize Novel Viral Proteins
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Phage portal proteins counteract stringent-response-mediated restriction.

Kristina Kronborg1, Luokai Wang1,2, Muriel Leandra Schicketanz1,3

  • 1Department of Biology, University of Copenhagen, Copenhagen, Denmark.

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|July 11, 2026
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Summary

Bacteriophage T7 uses its portal protein Gp8 to suppress the bacterial stringent response, a host defense mechanism. This interaction allows phages to overcome host-imposed barriers and replicate effectively.

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06:10

Following Cell-fate in E. coli After Infection by Phage Lambda

Published on: October 14, 2011

Area of Science:

  • Microbiology
  • Virology
  • Molecular Biology

Background:

  • Bacteria employ physiological states, including the stringent response, to limit viral replication.
  • The stringent response, mediated by alarmone nucleotides (ppGpp and pppGpp), creates a growth-restrictive environment hindering phage infection.

Purpose of the Study:

  • To investigate how bacteriophages overcome host-imposed barriers, specifically the stringent response.
  • To elucidate the mechanism by which bacteriophage T7 counteracts the stringent response.

Main Methods:

  • Investigated the interaction between bacteriophage T7's portal protein Gp8 and host stringent response regulators RelA and SpoT.
  • Utilized portal mutations to assess the impact on alarmone accumulation, phage replication, and lysis.
  • Examined portal proteins from other coliphages for similar stringent-response-linked features.

Main Results:

  • Bacteriophage T7's portal protein Gp8 directly engages RelA and SpoT, inhibiting their synthetase activity and suppressing alarmone accumulation.
  • Mutations in Gp8 that disrupt this interaction lead to sustained alarmone elevation, delayed lysis, and impaired phage replication.
  • The negative impact of portal mutations is alleviated in alarmone-deficient host strains.
  • Similar stringent-response-linked features were observed in portal proteins of other coliphages.

Conclusions:

  • Bacterial stringent response acts as a significant barrier to phage infection.
  • Bacteriophage portal proteins possess a dual role, acting as essential virion components and antagonists of host stress physiology.
  • This mechanism of counteracting host stringent response is conserved among coliphages, highlighting a common viral strategy.