A phage satellite manipulates the viral DNA packaging motor to inhibit phage and promote satellite spread
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Updated: Jun 27, 2025

Phage-Mediated Genetic Manipulation of the Lyme Disease Spirochete Borrelia burgdorferi
Published on: September 28, 2022
Caroline M Boyd1, Kimberley D Seed1
1Plant and Microbial Biology, University of California - Berkeley, Berkeley, CA, 94720, USA.
Abstract:
ICP1, a lytic bacteriophage of Vibrio cholerae, is parasitized by phage satellites, PLEs, which hijack ICP1 proteins for their own horizontal spread. PLEs' dependence on ICP1's DNA replication machinery, and virion components results in inhibition of ICP1's lifecycle. PLEs' are expected to depend on ICP1 factors for genome packaging, but the mechanism(s) PLEs use to inhibit ICP1 genome packaging is currently unknown. Here, we identify and characterize Gpi, PLE's indiscriminate genome packaging inhibitor. Gpi binds to ICP1's large terminase (TerL), the packaging motor, and blocks genome packaging. To overcome Gpi's negative effect on TerL, a component PLE also requires, PLE uses two genome packaging specifiers, GpsA and GpsB, that specifically allow packaging of PLE genomes. Surprisingly, PLE also uses mimicry of ICP1's pac site as a backup strategy to ensure genome packaging. PLE's pac site mimicry, however, is only sufficient if PLE can inhibit ICP1 at other stages of its lifecycle, suggesting an advantage to maintaining Gpi, GpsA, and GpsB. Collectively, these results provide mechanistic insights into another stage of ICP1's lifecycle that is inhibited by PLE, which is currently the most inhibitory of the documented phage satellites. More broadly, Gpi represents the first satellite-encoded inhibitor of a phage TerL.
Insights
Phage satellites (PLEs) inhibit Vibrio cholerae phage ICP1 packaging by blocking its motor (TerL) with Gpi. PLEs use specific factors (GpsA, GpsB) and mimicry to package their own DNA, representing a novel phage-ICP1 interaction.
Area of Science:
- Microbiology
- Virology
- Molecular Biology
Background:
- Bacteriophages like ICP1 are crucial in controlling bacterial populations, including pathogens like Vibrio cholerae.
- Phage satellites (PLEs) are genetic elements that depend on helper phages, like ICP1, for replication and spread.
- PLEs interfere with ICP1's lifecycle, but the mechanisms inhibiting ICP1's genome packaging were previously unknown.
Conclusions:
- PLEs possess sophisticated mechanisms to inhibit ICP1's lifecycle, including blocking its DNA packaging machinery.
- Gpi is the first identified satellite-encoded inhibitor targeting a phage TerL, highlighting novel host-parasite dynamics.
- The multifaceted strategy of PLEs ensures their propagation at the expense of the helper phage ICP1, making them highly effective inhibitors.
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