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A Host-Produced Quorum-Sensing Autoinducer Controls a Phage Lysis-Lysogeny Decision.
Justin E Silpe1, Bonnie L Bassler2
1Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Cell
|December 18, 2018
Summary
Vibrio cholerae and its phages use the same signal molecule, DPO, for pathogenesis. Phage VqmA activates host virulence genes, while host VqmA represses them, revealing a complex interplay in bacterial infection.
Area of Science:
- Microbiology
- Molecular Biology
- Bacteriology
Background:
- Vibrio cholerae utilizes a quorum-sensing (QS) system involving 3,5-dimethylpyrazin-2-ol (DPO) and VqmA (VqmAVc) to regulate virulence and biofilm formation.
- The vqmA gene is found in Vibrio species and in the vibriophage VP882, suggesting horizontal gene transfer and shared regulatory mechanisms.
Purpose of the Study:
- To investigate the role of phage-encoded VqmA (VqmAPhage) in the interaction between V. cholerae and its infecting phage.
- To understand how phages integrate host-derived signals into their life cycle decisions (lysis-lysogeny).
- To explore the potential for reprogramming phages to control bacterial infections.
Main Methods:
- Comparative analysis of VqmAVc and VqmAPhage interactions with DPO.
- Investigation of phage antirepressor function and its interference with related phage repressors.
- Functional assays to assess the activation of host VqmAVc regulon by VqmAPhage.
- Reprogramming of phages to respond to user-defined cues for lysis induction.
Main Results:
- Phage VqmAPhage binds to host-produced DPO, initiating the phage lysis program.
- VqmAPhage acts via an antirepressor that inactivates the phage repressor and interferes with related phage repressors.
- VqmAPhage activates the host VqmAVc regulon, demonstrating an asymmetric regulatory interaction.
- Host VqmAVc cannot induce phage-mediated lysis, highlighting unidirectional phage influence.
Conclusions:
- Both V. cholerae and its infecting phages rely on the same signal molecule (DPO) for pathogenesis.
- Phages leverage host QS machinery for their own propagation, integrating host signals into lysis-lysogeny decisions.
- Reprogramming phages offers a potential strategy for therapeutic intervention against bacterial infections.
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