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1. Factor for Inversion Stimulation Connects Two Sensory Pathways, Quorum Sensing and Surface Sensing, to Control Motility in Vibrio parahaemolyticus

   https://doi.org/doi.org/10.3389/fmicb.2021.669447  

   Jessica G. Tague, Abish Regmi (October 2021, Frontiers in microbiology)

   null (Ed.)

   Factor for inversion stimulation is a global regulator that is highly expressed during exponential phase growth and undetectable in stationary phase growth. Quorum sensing (QS) is a global regulatory mechanism that controls gene expression in response to changes in cell density and growth phase. In Vibrio parahaemolyticus, a marine species and a significant human pathogen, the QS regulatory sRNAs, Qrr1 to Qrr5, are expressed during exponential growth and negatively regulate the high cell density QS master regulator OpaR. OpaR is a positive regulator of capsule polysaccharide (CPS) formation, which is required for biofilm formation, and is a repressor of lateral flagella required for swarming motility. In V. parahaemolyticus, we show that Fis is a positive regulator of the qrr sRNAs expression. In an in-frame fis deletion mutant, qrr expression was repressed and opaR expression was induced. The Δfis mutant produced CPS and biofilm, but swarming motility was abolished. Also, the fis deletion mutant was more sensitive to polymyxin B. Swarming motility requires expression of both the surface sensing scrABC operon and lateral flagella laf operon. Our data showed that in the Δfis mutant both laf and scrABC genes were repressed. Fis controlled swarming motility indirectly through the QS pathway and directly through the surface sensing pathway. To determine the effects of Fis on cellular metabolism, we performed in vitro growth competition assays, and found that Δfis was outcompeted by wild type in minimal media supplemented with intestinal mucus as a sole nutrient source. The data showed that Fis positively modulated mucus components L-arabinose, D-gluconate and N-acetyl-D-glucosamine catabolism gene expression. In an in vivo colonization competition assay, Δfis was outcompeted by wild type, indicating Fis is required for fitness. Overall, these data demonstrate a global regulatory role for Fis in V. parahaemolyticus that includes QS, motility, and metabolism. 

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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 biophysical limit for quorum sensing in biofilms

   https://doi.org/10.1073/pnas.2022818118  

   Narla, Avaneesh V.; Borenstein, David Bruce; Wingreen, Ned S. (May 2021, Proceedings of the National Academy of Sciences)

   null (Ed.)

   Bacteria grow on surfaces in complex immobile communities known as biofilms, which are composed of cells embedded in an extracellular matrix. Within biofilms, bacteria often interact with members of their own species and cooperate or compete with members of other species via quorum sensing (QS). QS is a process by which microbes produce, secrete, and subsequently detect small molecules called autoinducers (AIs) to assess their local population density. We explore the competitive advantage of QS through agent-based simulations of a spatial model in which colony expansion via extracellular matrix production provides greater access to a limiting diffusible nutrient. We note a significant difference in results based on whether AI production is constitutive or limited by nutrient availability: If AI production is constitutive, simple QS-based matrix-production strategies can be far superior to any fixed strategy. However, if AI production is limited by nutrient availability, QS-based strategies fail to provide a significant advantage over fixed strategies. To explain this dichotomy, we derive a biophysical limit for the dynamic range of nutrient-limited AI concentrations in biofilms. This range is remarkably small (less than 10-fold) for the realistic case in which a growth-limiting diffusible nutrient is taken up within a narrow active growth layer. This biophysical limit implies that for QS to be most effective in biofilms AI production should be a protected function not directly tied to metabolism. 

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4. 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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5. Quorum sensing mediates morphology and motility transitions in the model archaeon Haloferax volcanii

   https://doi.org/10.1128/mbio.00906-25  

   Chatterjee, Priyanka; Consoli, Caroline E; Schiller, Heather; Winter, Kiersten K; McCallum, Monica E; Schulze, Stefan; Pohlschroder, Mechthild (June 2025, mBio)

   Newman, Dianne K (Ed.)

   ABSTRACT Quorum sensing (QS) is a population density-dependent mechanism of intercellular communication, whereby microbes secrete and detect signals to regulate behaviors such as virulence and biofilm formation. Although QS is well-studied in bacteria, little is known about cell-cell communication in archaea. The model archaeonHaloferax volcaniican transition from motile rod-shaped cells to non-motile disks as population density increases. In this report, we demonstrate that this transition is induced by a secreted small molecule present in cell-free conditioned medium (CM). The CM also elicits a response from a bacterial QS bioreporter, suggesting the potential for inter-domain crosstalk. To investigate theHfx. volcaniiQS response, we performed quantitative proteomics and detected significant differential abundances of 236 proteins in the presence of CM, including proteins involved in cell structure, motility, glycosylation, and two-component systems. We also demonstrate that a mutant lacking the cell shape regulatory factor DdfA does not undergo shape and motility transitions in the presence of CM, allowing us to identify protein abundance changes in the QS response pathway separate from those involved in shape and motility. In the ∆ddfAstrain, only 110 proteins had significant differential abundance, and comparative analysis of these two proteomics experiments enabled us to identify proteins dependent on and independent of DdfA in the QS response pathway. Our study provides the first detailed analysis of QS pathways in any archaeon, strengthening our understanding of archaeal communication as well as providing the framework for studying intra- and interdomain crosstalk. IMPORTANCEUnderstanding the complex signaling networks in microbial communities has led to many invaluable applications in medicine and industry. Yet, while archaea are ubiquitous and play key roles in nutrient cycling, little is known about the roles of archaeal intra- and interspecies cell-cell communication in environments such as the human, soil, and marine microbiomes. In this study, we established the first robust system for studying quorum sensing in archaea by using the model archaeonHaloferax volcanii. We demonstrated that different behaviors, such as cell shape and motility, are mediated by a signal molecule, and we uncovered key regulatory components of the signaling pathway. This work advances our understanding of microbial communication, shedding light on archaeal intra- and interdomain interactions, and contributes to a more complete picture of the interconnected networks of life on Earth. 

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