Figure 6: Quorum-sensing controls the lysis-lysogeny fate decision in phage VP882.

(A) Phage VP882 (multi-colored ring) can lyse or lysogenize its vibrio host. In the lysogenic state, Q (blue) production is repressed by cI (green). Lysis depends on inactivation of cI activity, and that is mediated by two independent inputs, host DNA damage or QS. Host DNA damage (lightning bolt) leads to RecA-assisted proteolysis (scissors) of the cI repressor. The QS input is mediated by VqmA_Phage (purple) binding to the host-produced DPO AI, which is derived from threonine via the Tdh enzyme. VqmA_Phage bound to DPO activates expression of qtip (red). Qtip aggreagates the cI protein. Irrespective of the input, reduced cI activity leads to derepression of q and subsequent expression of genes involved in lysis (yellow). VqmA_Phage, when bound to host DPO, also activates transcription of the host VqmA QS target, vqmR, leading to production of the sRNA VqmR. The VqmR regulon includes genes required for biofilm formation. (B) Growth of WT and Δtdh V. cholerae lysogens. Left; carrying inducible vqmA_Phage on a plasmid. Right; carrying inducible qtip on a plasmid. Top; no addition. Bottom; with 100 μM DPO. All strains carry phage VP882 vqmA_Phage::Tn₅. When present, as indicated in the associated keys, the inducers of vqmA_Phage and qtip (arabinose and aTc, respectively), were present at 0.035% and 10 ng mL⁻¹, respectively. (C) qPCR of phage DNA prepared from the samples in (B). Black; Δtdh, white; WT V. cholerae. Viral Load is the amount of VP882-specific DNA in the induced samples relative to the uninduced samples, in all cases relative to DNA of a non-phage plasmid (see Methods). Data are represented as mean ± std with n=3 biological replicates (B) and as mean ± sem with n=3 biological replicates and n=4 technical replicates (C). See also Figures S6 and S7.