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1. Natural and synthetic inhibitors of a phage-encoded quorum-sensing receptor affect phage–host dynamics in mixed bacterial communities

   https://doi.org/10.1073/pnas.2217813119  

   Silpe, Justin E.; Duddy, Olivia P.; Bassler, Bonnie L. (December 2022, Proceedings of the National Academy of Sciences)

   Viruses that infect bacteria, called phages, shape the composition of bacterial communities and are important drivers of bacterial evolution. We recently showed that temperate phages, when residing in bacteria (i.e., prophages), are capable of manipulating the bacterial cell-to-cell communication process called quorum sensing (QS). QS relies on the production, release, and population-wide detection of signaling molecules called autoinducers (AI). Gram-negative bacteria commonly employ N -acyl homoserine lactones (HSL) as AIs that are detected by LuxR-type QS receptors. Phage ARM81ld is a prophage of the aquatic bacterium Aeromonas sp. ARM81, and it encodes a homolog of a bacterial LuxR, called LuxR ARM81ld . LuxR ARM81ld detects host Aeromonas -produced C4-HSL, and in response, activates the phage lytic program, triggering death of its host and release of viral particles. Here, we show that phage LuxR ARM81ld activity is modulated by noncognate HSL ligands and by a synthetic small molecule inhibitor. We determine that HSLs with acyl chain lengths equal to or longer than C8 antagonize LuxR ARM81ld . For example, the C8-HSL AI produced by Vibrio fischeri that coexists with Aeromonads in aquatic environments, binds to and inhibits LuxR ARM81ld , and consequently, protects the host from lysis. Coculture of V. fischeri with the Aeromonas sp. ARM81 lysogen suppresses phage ARM81ld virion production. We propose that the cell density and species composition of the bacterial community could determine outcomes in bacterial-phage partnerships. 

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2. Phage Infection Restores PQS Signaling and Enhances Growth of a Pseudomonas aeruginosa lasI Quorum-Sensing Mutant

   https://doi.org/10.1128/jb.00557-21  

   Høyland-Kroghsbo, Nina Molin; Bassler, Bonnie L. (January 2022, Journal of Bacteriology)

   Bondy-Denomy, Joseph (Ed.)

   ABSTRACT Chemical communication between bacteria and between bacteria and the bacteriophage (phage) viruses that prey on them can shape the outcomes of phage-bacterial encounters. Quorum sensing (QS) is a bacterial cell-to-cell communication process that promotes collective undertaking of group behaviors. QS relies on the production, release, accumulation, and detection of signal molecules called autoinducers. Phages can exploit QS-mediated communication to manipulate their hosts and maximize their own survival. In the opportunistic pathogen Pseudomonas aeruginosa , the LasI/R QS system induces the RhlI/R QS system, and in opposing manners, these two systems control the QS system that relies on the autoinducer called PQS. A P. aeruginosa Δ lasI mutant is impaired in PQS synthesis, leading to accumulation of the precursor molecule HHQ, and HHQ suppresses growth of the P. aeruginosa Δ lasI strain. We show that, in response to a phage infection, the P. aeruginosa Δ lasI mutant reactivates QS, which, in turn, restores pqsH expression, enabling conversion of HHQ into PQS. Moreover, downstream QS target genes encoding virulence factors are induced. Additionally, phage-infected P. aeruginosa Δ lasI cells transiently exhibit superior growth compared to uninfected cells. IMPORTANCE Clinical isolates of P. aeruginosa frequently harbor mutations in particular QS genes. Here, we show that infection by select temperate phages restores QS, a cell-to-cell communication mechanism in a P. aeruginosa QS mutant. Restoration of QS increases expression of genes encoding virulence factors. Thus, phage infection of select P. aeruginosa strains may increase bacterial pathogenicity, underscoring the importance of characterizing phage-host interactions in the context of bacterial mutants that are relevant in clinical settings. 

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3. 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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4. 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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5. Natural silencing of quorum-sensing activity protects Vibrio parahaemolyticus from lysis by an autoinducer-detecting phage

   https://doi.org/10.1371/journal.pgen.1010809  

   Duddy, Olivia P.; Silpe, Justin E.; Fei, Chenyi; Bassler, Bonnie L. (July 2023, PLOS Genetics)

   Matic, Ivan (Ed.)

   Quorum sensing (QS) is a chemical communication process that bacteria use to track population density and orchestrate collective behaviors. QS relies on the production, accumulation, and group-wide detection of extracellular signal molecules called autoinducers. Vibriophage 882 (phage VP882), a bacterial virus, encodes a homolog of theVibrioQS receptor-transcription factor, called VqmA, that monitors theVibrioQS autoinducer DPO. Phage VqmA binds DPO at high host-cell density and activates transcription of the phage geneqtip. Qtip, an antirepressor, launches the phage lysis program. Phage-encoded VqmA when bound to DPO also manipulates host QS by activating transcription of the host genevqmR. VqmR is a small RNA that controls downstream QS target genes. Here, we sequenceVibrio parahaemolyticusstrain O3:K6 882, the strain from which phage VP882 was initially isolated. The chromosomal region normally encodingvqmRandvqmAharbors a deletion encompassingvqmRand a portion of thevqmApromoter, inactivating that QS system. We discover thatV.parahaemolyticusstrain O3:K6 882 is also defective in its other QS systems, due to a mutation inluxO, encoding the central QS transcriptional regulator LuxO. Both thevqmR-vqmAandluxOmutations lockV.parahaemolyticusstrain O3:K6 882 into the low-cell density QS state. Reparation of the QS defects inV.parahaemolyticusstrain O3:K6 882 promotes activation of phage VP882 lytic gene expression and LuxO is primarily responsible for this effect. Phage VP882-infected QS-competentV.parahaemolyticusstrain O3:K6 882 cells lyse more rapidly and produce more viral particles than the QS-deficient parent strain. We propose that, inV.parahaemolyticusstrain O3:K6 882, constitutive maintenance of the low-cell density QS state suppresses the launch of the phage VP882 lytic cascade, thereby protecting the bacterial host from phage-mediated lysis. 

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