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1. Vibrio parahaemolyticus quorum sensing controls phage VP882 transmission

   https://doi.org/10.1128/mbio.00737-26  

   Sargen, Molly R; Bassler, Bonnie L (May 2026, mBio)

   Penades, José (Ed.)

   ABSTRACT Quorum sensing is a cell-to-cell communication process bacteria use to orchestrate collective behaviors. Quorum sensing involves the production, release, and detection of extracellular signal molecules called autoinducers. Some temperate phages can monitor bacterial autoinducers, enabling them to track the abundance of potential host cells in the vicinity. Quorum-sensing-responsive phages can preferentially launch the transition from lysogeny to lytic replication at high cell density, presumably maximizing transmission. Once the phage lytic program is enacted, if nearby host cells are already lysogens, infections initiated by released virions could be nonproductive due to homoimmunity or superinfection exclusion mechanisms, posing a conundrum for temperate phages, including those that surveil quorum-sensing autoinducers. Here, we define host and phage components that influence the transmission of the first-discovered quorum-sensing-responsive phage, phage VP882, in populations of its host,Vibrio parahaemolyticus. We show that phage VP882 uses the K-antigen of serotype O3:K6 as its receptor. We demonstrate that host cells can prevent phage access to the O3:K6 K-antigen via quorum-sensing control of the export of polysaccharides that shield the K-antigen from the phage at high cell density. We discover that phage VP882 can superinfect and superlysogenizeV. parahaemolyticus, overcoming the challenge of detecting whether or not potential hosts are lysogens. Following superlysogenization, recombination of the resident and newly infecting phage genomes can occur, possibly promoting phage VP882 genome diversification. IMPORTANCEA longstanding mystery is how temperate phages optimally time the launch of their lytic cascades to maximize spread. Quorum-sensing-responsive phages can preferentially execute their lytic replication programs at high host cell density, which in principle should foster transmission. However, if nearby host cells are already lysogens, infections initiated by released virions could be nonproductive due to homoimmunity or superinfection exclusion. We define host and phage components influencing the transmission of the quorum-sensing-responsive phage VP882 inVibrio parahaemolyticuspopulations. Phage VP882 uses the O3:K6 K-antigen as its receptor. Host cells prevent phage infection via quorum-sensing-controlled export of polysaccharides that shield the K-antigen at high cell density. We discover that phage VP882 can superinfect and superlysogenizeV. parahaemolyticus, overcoming the challenge of detecting whether or not potential hosts are lysogens. These findings reveal how phages can capitalize on interception of host quorum-sensing cues to maximize their reproductive success. 

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2. The LuxO-OpaR quorum-sensing cascade differentially controls Vibriophage VP882 lysis-lysogeny decision making in liquid and on surfaces

   https://doi.org/10.1371/journal.pgen.1011243  

   Santoriello, Francis J; Bassler, Bonnie L (July 2024, PLOS Genetics)

   Dalia, Ankur B (Ed.)

   Quorum sensing (QS) is a process of cell-to-cell communication that bacteria use to synchronize collective behaviors. QS relies on the production, release, and group-wide detection of extracellular signaling molecules called autoinducers.Vibrios use two QS systems: the LuxO-OpaR circuit and the VqmA-VqmR circuit. Both QS circuits control group behaviors including biofilm formation and surface motility. TheVibrio parahaemolyticustemperate phage φVP882 encodes a VqmA homolog (called VqmAφ). When VqmAφ is produced by φVP882 lysogens, it binds to the host-produced autoinducer called DPO and launches the φVP882 lytic cascade. This activity times induction of lysis with high host cell density and presumably promotes maximal phage transmission to new cells. Here, we explore whether, in addition to induction from lysogeny, QS controls the initial establishment of lysogeny by φVP882 in naïve host cells. Using mutagenesis, phage infection assays, and phenotypic analyses, we show that φVP882 connects its initial lysis-lysogeny decision to both host cell density and whether the host resides in liquid or on a surface. Host cells in the low-cell-density QS state primarily undergo lysogenic conversion. The QS regulator LuxO~P promotes φVP882 lysogenic conversion of low-cell-density planktonic host cells. By contrast, the ScrABC surface-sensing system regulates lysogenic conversion of low-cell-density surface-associated host cells. ScrABC controls the abundance of the second messenger molecule cyclic diguanylate, which in turn, modulates motility. ThescrABCoperon is only expressed when its QS repressor, OpaR, is absent. Thus, at low cell density, QS-dependent derepression ofscrABCdrives lysogenic conversion in surface-associated host cells. These results demonstrate that φVP882 integrates cues from multiple sensory pathways into its lifestyle decision making upon infection of a new host cell. 

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3. Mechanism underlying the DNA-binding preferences of the Vibrio cholerae and vibriophage VP882 VqmA quorum-sensing receptors

   https://doi.org/10.1371/journal.pgen.1009550  

   Duddy, Olivia P.; Huang, Xiuliang; Silpe, Justin E.; Bassler, Bonnie L. (July 2021, PLOS Genetics)

   Crosson, Sean (Ed.)

   Quorum sensing is a chemical communication process that bacteria use to coordinate group behaviors. In the global pathogen Vibrio cholerae , one quorum-sensing receptor and transcription factor, called VqmA (VqmA Vc ), activates expression of the vqmR gene encoding the small regulatory RNA VqmR, which represses genes involved in virulence and biofilm formation. Vibriophage VP882 encodes a VqmA homolog called VqmA Phage that activates transcription of the phage gene qtip , and Qtip launches the phage lytic program. Curiously, VqmA Phage can activate vqmR expression but VqmA Vc cannot activate expression of qtip . Here, we investigate the mechanism underlying this asymmetry. We find that promoter selectivity is driven by each VqmA DNA-binding domain and key DNA sequences in the vqmR and qtip promoters are required to maintain specificity. A protein sequence-guided mutagenesis approach revealed that the residue E194 of VqmA Phage and A192, the equivalent residue in VqmA Vc , in the helix-turn-helix motifs contribute to promoter-binding specificity. A genetic screen to identify VqmA Phage mutants that are incapable of binding the qtip promoter but maintain binding to the vqmR promoter delivered additional VqmA Phage residues located immediately C-terminal to the helix-turn-helix motif as required for binding the qtip promoter. Surprisingly, these residues are conserved between VqmA Phage and VqmA Vc . A second, targeted genetic screen revealed a region located in the VqmA Vc DNA-binding domain that is necessary to prevent VqmA Vc from binding the qtip promoter, thus restricting DNA binding to the vqmR promoter. We propose that the VqmA Vc helix-turn-helix motif and the C-terminal flanking residues function together to prohibit VqmA Vc from binding the qtip promoter. 

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4. A family of linear plasmid phages that detect a quorum-sensing autoinducer exists in multiple bacterial species

   https://doi.org/10.1128/mbio.02320-25  

   Santoriello, Francis J; Bassler, Bonnie L (January 2026, mBio)

   Hatfull, Graham F (Ed.)

   ABSTRACT Temperate phages oscillate between lysogeny, a genomic maintenance state within a bacterial host, and lytic replication, in which the host is killed, and newly made phage particles are released. Successful transmission to new hosts requires that temperate phages appropriately time their transitions from lysogeny to lysis. It is well understood that temperate phages trigger lysis upon detection of host cell stress. Understanding of the breadth of cues that induce lysis expanded with the discovery of phages carrying quorum-sensing receptor genes that promote lytic induction exclusively at high host cell density. Bacteria engage in a cell-cell communication process called quorum sensing, which relies on the production, release, accumulation, and group-wide detection of extracellular signal molecules called autoinducers. Bacteria use quorum sensing to monitor changes in population density and synchronize collective behaviors. The temperate phage VP882 (φVP882) encodes VqmAφ—a homolog of its host’s quorum-sensing receptor/transcription factor VqmA. VqmAφ allows φVP882 to detect the accumulation of the host autoinducer called DPO. Presumably, launching the lytic induction program at high host cell density maximizes φVP882 transmission to new hosts. Here, by mining sequence databases for linear plasmid phages, we identify VP882-like phages in multiple DPO-producing bacterial species isolated at diverse times and geographic locations. We show that the VqmAφ homologs can indeed detect DPO and, in response, activate the lytic pathway. Our findings indicate that φVP882 is a member of a family of globally dispersed temperate phages that possess the potential to respond to host quorum sensing. IMPORTANCEThe discovery of quorum-sensing responsive linear plasmid phages has transformed understanding of phage-bacterial interactions by demonstrating inter-domain chemical communication. To date, however, examples of quorum-sensing responsive phages have been sparse. The founding example of such a phage, φVP882, detects a chemical communication signal molecule called DPO that is produced by diverse bacterial species. We investigated whether a family of VP882-like phages might exist that detect and respond to DPO. We find that indeed, VP882-like phages reside in DPO-producing bacterial species isolated at different times and geographic locations, suggesting their wide circulation in the environment. This discovery strengthens the evidence for the generality of phage-bacterial inter-domain chemical communication. 

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5. A transcription factor-sRNA-mediated double-negative feedback loop confers pathogen-specific control of quorum-sensing genes

   https://doi.org/10.1128/mbio.00633-26  

   Mashruwala, Ameya A; Decker, Kaitlin; Fei, Chenyi; Valastyan, Julie; Bassler, Bonnie L (May 2026, mBio)

   Whiteley, Marvin (Ed.)

   ABSTRACT The cell-to-cell communication process called quorum sensing enables bacteria to synchronize collective behaviors. Quorum sensing relies on the production, release, and detection of signaling molecules called autoinducers. InVibrio cholerae, the VqmA transcription factor, following binding of the DPO autoinducer, activates the expression of the gene encoding the VqmR small regulatory RNA. VqmR controls traits including biofilm formation. Here, we identify repressors of DPO-VqmA-VqmR signaling. We focus on one identified repressor, the LuxT transcription factor. We show that LuxT repressesvqmRtranscription. VqmR post-transcriptionally repressesluxTtranslation. This arrangement forms a double-negative feedback loop between the two regulators. Reciprocal control hinges on the N-terminal eight amino acids of LuxT. The nucleotide sequence encoding this LuxT region serves as the VqmR binding site in theluxTmRNA and the amino acids specified by this same N-terminal region are required for LuxT to bind thevqmRpromoter. This same LuxT N-terminal region also expands the DNA motifs to which LuxT can bind. We show this regulatory circuit is unique toV. choleraeand closely related species and absent from other vibrios. We define the set of LuxT-controlled genes inV. choleraeand show that LuxT promotes biofilm formation, a key requirement for successful colonization of eukaryotic hosts.IMPORTANCEBacterial quorum sensing enables control of collective behaviors. InVibrio cholerae, the DPO-VqmA-VqmR quorum-sensing circuit governs key processes, including biofilm formation. Here, we identify a double-negative feedback loop between the transcription factor LuxT and the small RNA VqmR. This regulatory circuit depends on an eight amino acid N-terminal region that exists only inV. choleraeLuxT and LuxT from its close relatives. This short peptide sequence confers three distinct functions: it enables LuxT to repressvqmR, rendersluxTmRNA susceptible to VqmR repression, and governs which DNA motifs LuxT can bind. Our findings reveal a pathogen-specific regulatory module that links small RNA targeting of mRNAs to transcription factor DNA binding specificity. The results show how evolution tailors bacterial regulatory circuits to adapt to different environments. 

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