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Structural Insights into Regulation of Vibrio Virulence Gene Networks

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Vibrio spp. Infections

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1404))

Abstract

One of the best studied aspects of pathogenic Vibrios are the virulence cascades that lead to the production of virulence factors and, ultimately, clinical outcomes. In this chapter, we will examine the regulation of Vibrio virulence gene networks from a structural and biochemical perspective. We will discuss the recent research into the numerous proteins that contribute to regulating virulence in Vibrio spp such as quorum sensing regulator HapR, the transcription factors AphA and AphB, or the virulence regulators ToxR and ToxT. We highlight how insights gained from these studies are already illuminating the basic molecular mechanisms by which the virulence cascade of pathogenic Vibrios unfold and contend that understanding how protein interactions contribute to the host–pathogen communications will enable the development of new antivirulence compounds that can effectively target these pathogens.

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References

  • Alam A, Tam V, Hamilton E, Dziejman M (2010) vttRA and vttRB encode ToxR family proteins that mediate bile-induced expression of type three secretion system genes in a non-O1/non-O139 Vibrio cholerae strain. Infect Immun 78:2554–2570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Almagro-Moreno S, Pruss K, Taylor RK (2015a) Intestinal colonization dynamics of Vibrio cholerae. PLoS Pathog 11:e1004787

    Article  PubMed  PubMed Central  Google Scholar 

  • Almagro-Moreno S, Root MZ, Taylor RK (2015b) Role of ToxS in the proteolytic cascade of virulence regulator ToxR in Vibrio cholerae. Mol Microbiol 98:963–976

    Article  CAS  PubMed  Google Scholar 

  • Aravind L, Anantharaman V, Balaji S, Babu MM, Iyer LM (2005) The many faces of the helix-turn-helix domain: transcription regulation and beyond. FEMS Microbiol Rev 29:231–262

    Article  CAS  PubMed  Google Scholar 

  • Ball AS, Chaparian RR, van Kessel JC (2017) Quorum sensing gene regulation by LuxR/HapR master regulators in Vibrios. J Bacteriol 199

    Google Scholar 

  • Barthelmebs L, Lecomte B, Divies C, Cavin J-F (2000) Inducible metabolism of phenolic acids in Pediococcus pentosaceus is encoded by an autoregulated operon which involves a new class of negative transcriptional regulator. J Bacteriol 182:6724–6731

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bellair M, Withey JH (2008) Flexibility of Vibrio cholerae ToxT in transcription activation of genes having altered promoter spacing. J Bacteriol 190:7925–7931

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blanco AG, Solà M, Gomis-Rüth FX, Coll M (2002) Tandem DNA recognition by PhoB, a two-component signal transduction transcriptional activator. Structure 10:701–713

    Article  CAS  PubMed  Google Scholar 

  • Bosire EM et al (2020) Diffusible signal factors act through AraC-type transcriptional regulators as chemical cues to repress virulence of enteric pathogens. Infect Immun 1–37. https://doi.org/10.1128/IAI.00226-20

  • Cegelski L, Marshall GR, Eldridge GR, Hultgren SJ (2008) The biology and future prospects of antivirulence therapies. Nat Rev Microbiol 6:17–27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chatterjee A, Dutta PK, Chowdhury R (2007) Effect of fatty acids and cholesterol present in bile on expression of virulence factors and motility of Vibrio cholerae. Infect Immun 75:1946–1953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Childers BM et al (2011) N-terminal residues of the Vibrio cholerae virulence regulatory protein ToxT involved in dimerization and modulation by fatty acids. J Biol Chem 286:28644–28655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clemens JD, Nair GB, Ahmed T, Qadri F, Holmgren J (2017) Cholera. Lancet Glob Health 2018(390):1539–1549

    Google Scholar 

  • Conte LM, Carroll KS (2013) The redox biochemistry of protein sulfenylation and sulfinylation. J Biol Chem 288:26480–26488

    Article  PubMed  PubMed Central  Google Scholar 

  • Crawford JA, Kaper JB, DiRita VJ (1998) Analysis of ToxR-dependent transcription activation of ompU, the gene encoding a major envelope protein in Vibrio cholerae. Mol Microbiol 29:235–246

    Article  CAS  PubMed  Google Scholar 

  • Crawford JA, Krukonis ES, DiRita VJ (2003) Membrane localization of the ToxR winged-helix domain is required for TcpP-mediated virulence gene activation in Vibrio cholerae. Mol Microbiol 47:1459–1473

    Article  CAS  PubMed  Google Scholar 

  • Cruite J, Succo P, Raychaudhuri S, Kull FJ (2018) Crystal structure of an inactive variant of the quorum-sensing master regulator HapR from the protease-deficient non-O1, non-O139 Vibrio cholerae strain V2. Acta Crystallogr F Struct Biol Commun 74:331–336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cruite JT et al (2019) Structural basis for virulence regulation in Vibrio cholerae by unsaturated fatty acid components of bile. Commun Biol 2:440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cuthbertson L, Nodwell JR (2013) The TetR family of regulators. Microbiol Mol Biol Rev 77:440–475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Silva RS et al (2005) Crystal structure of the virulence gene activator AphA from Vibrio cholerae reveals it is a novel member of the winged helix transcription factor superfamily. J Biol Chem 280:13779–13783

    Article  PubMed  Google Scholar 

  • De Silva RS et al (2007) Crystal structure of the Vibrio cholerae quorum-sensing regulatory protein HapR. J Bacteriol 189:5683–5691

    Article  PubMed  PubMed Central  Google Scholar 

  • DiRita VJ, Mekalanos JJ (1991) Periplasmic interaction between two membrane regulatory proteins, ToxR and ToxS, results in signal transduction and transcriptional activation. Cell 64:29–37

    Article  CAS  PubMed  Google Scholar 

  • DiRita VJ, Parsot C, Jander G, Mekalanos JJ (1991) Regulatory cascade controls virulence in Vibrio cholerae. Proc Natl Acad Sci 88:5403–5407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dongre M et al (2011) Evidence on how a conserved glycine in the hinge region of HapR regulates its DNA binding ability: lessons from a natural variant. J Biol Chem 286:15043–15049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dziejman M, Mekalanos JJ (1994) Analysis of membrane protein interaction: ToxR can dimerize the amino terminus of phage lambda repressor. Mol Microbiol 13:485–494

    Article  CAS  PubMed  Google Scholar 

  • Dziejman M, Kolmar H, Fritz H-J, Mekalanos JJ (1999) ToxR co-operative interactions are not modulated by environmental conditions or periplasmic domain conformation. Mol Microbiol 31:305–317

    Article  CAS  PubMed  Google Scholar 

  • Elgaml A, Miyoshi S-I (2017) Regulation systems of protease and hemolysin production in Vibrio vulnificus. Microbiol Immunol 61:1–11

    Article  CAS  PubMed  Google Scholar 

  • Fan F et al (2014) Enhanced interaction of Vibrio cholerae virulence regulators TcpP and ToxR under oxygen-limiting conditions. Infect Immun 82:1676–1682

    Article  PubMed  PubMed Central  Google Scholar 

  • Finkelstein RA, Boesman-Finkelstein M, Chang Y, Hase CC (1991) Vibrio cholerae hemagglutinin/protease, colonial variation, virulence, and detachment. Infect Immun 60:472–478

    Article  Google Scholar 

  • Gao X et al (2017) Identification of the regulon of AphB and its essential roles in LuxR and exotoxin Asp expression in the pathogen Vibrio alginolyticus. J Bacteriol 199

    Google Scholar 

  • Golubeva YA, Ellermeier JR, Cott Chubiz JE, Slauch JM (2016) Intestinal long-chain fatty acids act as a direct signal to modulate expression of the Salmonella pathogenicity island 1 type III secretion system. MBio 7:e02170–e02115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gotoh K et al (2010) Bile acid-induced virulence gene expression of Vibrio parahaemolyticus reveals a novel therapeutic potential for bile acid sequestrants. PLoS One 5:e13365–e13312

    Article  PubMed  PubMed Central  Google Scholar 

  • Gubensäk N et al (2021a) The periplasmic domains of Vibrio cholerae ToxR and ToxS are forming a strong heterodimeric complex independent on the redox state of ToxR cysteines. Mol Microbiol 115:1277–1291

    Article  PubMed  PubMed Central  Google Scholar 

  • Gubensäk N et al (2021b) Structural and DNA-binding properties of the cytoplasmic domain of Vibrio cholerae transcription factor ToxR. J Biol Chem 297:101167

    Article  PubMed  PubMed Central  Google Scholar 

  • Gupta S, Chowdhury R (1997) Bile affects production of virulence factors and motility of Vibrio cholerae. Infect Immun 65:1131–1134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hase CC, Mekalanos JJ (1998) TcpP protein is a positive regulator of virulence gene expression in Vibrio cholerae. Proc Natl Acad Sci U S A 95:730–734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herrington DA et al (1988) Toxin, toxin-coregulated pili, and the toxR regulon are essential for Vibrio cholerae pathogenesis in humans. J Exp Med 168:1487–1492

    Article  CAS  PubMed  Google Scholar 

  • Higgins DE, Nazareno E, DiRita VJ (1992) The virulence gene activator ToxT from Vibrio cholerae is a member of the AraC family of transcriptional activators. J Bacteriol 174:6974–6980

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Holm L, Laakso LM (2016) Dali server update. Nucleic Acids Res 44:W351–W355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hubbard TP et al (2016) Genetic analysis of Vibrio parahaemolyticus intestinal colonization. Proc Natl Acad Sci U S A 113:6283–6288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hung DT, Shakhnovich EA, Pierson E, Mekalanos JJ (2005) Small-molecule inhibitor of Vibrio cholerae virulence and intestinal colonization. Science 310:670–674

    Article  CAS  PubMed  Google Scholar 

  • Jeong HG, Choi SH (2008) Evidence that AphB, essential for the virulence of Vibrio vulnificus, is a global regulator. J Bacteriol 190:3768–3773

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jers C et al (2018) The global acetylome of the human pathogen Vibrio cholerae V52 reveals lysine acetylation of major transcriptional regulators. Front Cell Infect Microbiol 7:537

    Article  PubMed  PubMed Central  Google Scholar 

  • Jo I et al (2019) Structural basis for HOCl recognition and regulation mechanisms of HypT, a hypochlorite-specific transcriptional regulator. Proc Natl Acad Sci U S A 116:3740–3745

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jobling MG, Holmes RK (1997) Characterization of hapR, a positive regulator of the Vibrio cholerae HA/protease gene hap, and its identification as a functional homologue of the Vibrio harveyi luxR gene. Mol Microbiol 26:1023. https://doi.org/10.1046/j.1365-2958.1997.6402011.x

    Article  CAS  PubMed  Google Scholar 

  • Kim Y et al (2010) Crystal structure of SmcR, a quorum-sensing master regulator of Vibrio vulnificus, provides insight into its regulation of transcription. J Biol Chem 285:14020–14030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim SM et al (2013) LuxR homologue SmcR is essential for Vibrio vulnificus pathogenesis and biofilm detachment, and its expression is induced by host cells. Infect Immun 81:3721–3730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim BS et al (2018) QStatin, a selective inhibitor of quorum sensing in Vibrio species. MBio 9

    Google Scholar 

  • Kodama T et al (2010) Two regulators of Vibrio parahaemolyticus play important roles in enterotoxicity by controlling the expression of genes in the Vp-PAI region. PLoS One 5:e8678–e8612

    Article  PubMed  PubMed Central  Google Scholar 

  • Kolmar H et al (1995) Membrane insertion of the bacterial signal transduction protein ToxR and requirements of transcription activation studied by modular replacement of different protein substructures. EMBO J 14:3895–3904

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kovacikova G, Skorupski K (1999) A Vibrio cholerae LysR homolog, AphB, cooperates with AphA at the tcpPH promoter to activate expression of the ToxR virulence cascade. J Bacteriol 181:4250–4256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kovacikova G, Skorupski K (2000) Differential activation of the tcpPH promoter by AphB determines biotype specificity of virulence gene expression in Vibrio cholerae. J Bacteriol 182:3228–3238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kovacikova G, Skorupski K (2001) Overlapping binding sites for the virulence gene regulators AphA, AphB and cAMP-CRP at the Vibrio cholerae tcpPH promoter. Mol Microbiol 41:393–407

    Article  CAS  PubMed  Google Scholar 

  • Kovacikova G, Skorupski K (2002) Regulation of virulence gene expression in Vibrio cholerae by quorum sensing: HapR functions at the aphA promoter. Mol Microbiol 46:1135–1147

    Article  CAS  PubMed  Google Scholar 

  • Kovacikova G, Lin W, Skorupski K (2004) Vibrio cholerae AphA uses a novel mechanism for virulence gene activation that involves interaction with the LysR-type regulator AphB at the tcpPH promoter. Mol Microbiol 53:129–142

    Article  CAS  PubMed  Google Scholar 

  • Kovacikova G, Lin W, Skorupski K (2010) The LysR-type virulence activator AphB regulates the expression of genes in Vibrio cholerae in response to low pH and anaerobiosis. J Bacteriol 192:4181–4191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krukonis ES, DiRita VJ (2003) DNA binding and ToxR responsiveness by the wing domain of TcpP, an activator of virulence gene expression in Vibrio cholerae. Mol Cell 12:157–165

    Article  CAS  PubMed  Google Scholar 

  • Krukonis ES, Yu RR, DiRita VJ (2000) The Vibrio cholerae ToxR/TcpP/ToxT virulence cascade: distinct roles for two membrane-localized transcriptional activators on a single promoter. Mol Microbiol 38:67–84

    Article  CAS  PubMed  Google Scholar 

  • Lembke M et al (2018) Proteolysis of ToxR is controlled by cysteine-thiol redox state and bile salts in Vibrio cholerae. Mol Microbiol 110:796–810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lembke M et al (2020) Host stimuli and operator binding sites controlling protein interactions between virulence master regulator ToxR and ToxS in Vibrio cholerae. Mol Microbiol 1–48:262. https://doi.org/10.1111/mmi.14510

    Article  CAS  Google Scholar 

  • Li CC, Crawford JA, DiRita VJ, Kaper JB (2000) Molecular cloning and transcriptional regulation of ompT, a ToxR-repressed gene in Vibrio cholerae. Mol Microbiol 35:189–203

    Article  PubMed  Google Scholar 

  • Li Y-C et al (2014) Structural dynamics of the two-component response regulator RstA in recognition of promoter DNA element. Nucleic Acids Res 42:8777–8788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li P et al (2016a) Bile salt receptor complex activates a pathogenic type III secretion system. eLife 5:1153

    Article  Google Scholar 

  • Li J, Wehmeyer G, Lovell S, Battaile KP, Egan SM (2016b) 1.65 Å resolution structure of the AraC-family transcriptional activator ToxT from Vibrio cholerae. Acta Crystallogr F Struct Biol Commun 72:726–731

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lim JG, Park JH, Choi SH (2014) Low cell density regulator AphA upregulates the expression of Vibrio vulnificus iscR gene encoding the Fe-S cluster regulator IscR. J Microbiol 52:413–421

    Article  CAS  PubMed  Google Scholar 

  • Liu Z et al (2011) Vibrio cholerae anaerobic induction of virulence gene expression is controlled by thiol-based switches of virulence regulator AphB. Proc Natl Acad Sci U S A 108:810–815

    Article  CAS  PubMed  Google Scholar 

  • Lowden MJ et al (2010) Structure of Vibrio cholerae ToxT reveals a mechanism for fatty acid regulation of virulence genes. Proc Natl Acad Sci U S A 107:2860–2865

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maddocks SE, Oyston PCF (2008) Structure and function of the LysR-type transcriptional regulator (LTTR) family proteins. Microbiology 154:3609–3623

    Article  CAS  PubMed  Google Scholar 

  • Mandal RS et al (2016) Ribavirin suppresses bacterial virulence by targeting LysR-type transcriptional regulators. Sci Rep 6:39454–39416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Markham LE, Tolbert JD, Kull FJ, Midgett CR, Micalizio GC (2021) An enantiodefined conformationally constrained fatty acid mimetic and potent inhibitor of ToxT. ACS Med Chem Lett 12:1493. https://doi.org/10.1021/acsmedchemlett.1c00378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martínez-Hackert E, Stock AM (1997) The DNA-binding domain of OmpR: crystal structures of a winged helix transcription factor. Structure 5:109–124

    Article  PubMed  Google Scholar 

  • Mathur J, Waldor MK (2004) The Vibrio cholerae ToxR-regulated porin OmpU confers resistance to antimicrobial peptides. Infect Immun 72:3577–3583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matson JS, Withey JH, DiRita VJ (2007) Regulatory networks controlling Vibrio cholerae virulence gene expression. Infect Immun 75:5542–5549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mey AR, Craig SA, Payne SM (2012) Effects of amino acid supplementation on porin expression and ToxR levels in Vibrio cholerae. Infect Immun 80:518–528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Midgett CR et al (2017) Bile salts and alkaline pH reciprocally modulate the interaction between the periplasmic domains of Vibrio cholerae ToxR and ToxS. Mol Microbiol 105:258–272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Midgett CR, Swindell RA, Pellegrini M, Jon Kull F (2020) A disulfide constrains the ToxR periplasmic domain structure, altering its interactions with ToxS and bile-salts. Sci Rep 10:9002–9011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Midgett CR, Talbot KM, Day JL, Munson GP, Kull FJ (2021) Structure of the master regulator Rns reveals an inhibitor of enterotoxigenic Escherichia coli virulence regulons. Sci Rep 11:15663–15613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller VL, Mekalanos JJ (1988) A novel suicide vector and its use in construction of insertion mutations: osmoregulation of outer membrane proteins and virulence determinants in Vibrio cholerae requires toxR. J Bacteriol 170:2575–2583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller VL, Taylor RK, Mekalanos JJ (1987) Cholera toxin transcriptional activator ToxR is a transmembrane DNA binding protein. Cell 48:271–279

    Article  PubMed  Google Scholar 

  • Miller VL, DiRita VJ, Mekalanos JJ (1989) Identification of toxS, a regulatory gene whose product enhances toxR-mediated activation of the cholera toxin promoter. J Bacteriol 171:1288–1293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller KA, Sofia MK, Weaver JWA, Seward CH, Dziejman M (2016) Regulation by ToxR-like proteins converges on vttRB expression to control type 3 secretion system-dependent caco2-bbe cytotoxicity in Vibrio cholerae. J Bacteriol 198:1675–1682

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morgan SJ et al (2011) The two faces of ToxR: activator of ompU, co-regulator of toxT in Vibrio cholerae. Mol Microbiol 81:113–128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morgan SJ, French EL, Plecha SC, Krukonis ES (2019) The wing of the ToxR winged helix-turn-helix domain is required for DNA binding and activation of toxT and ompU. PLoS One 14:e0221936–e0221919

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Newman JD et al (2021a) Amino acid divergence in the ligand-binding pocket of Vibrio LuxR/HapR proteins determines the efficacy of thiophenesulfonamide inhibitors. Mol Microbiol 116:1173. https://doi.org/10.1111/mmi.14804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Newman JD et al (2021b) The DNA binding domain of the Vibrio vulnificus SmcR transcription factor is flexible and binds diverse DNA sequences. Nucleic Acids Res 49:5967–5984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ottemann KM, Mekalanos JJ (1995) Analysis of Vibrio cholerae ToxR function by construction of novel fusion proteins. Mol Microbiol 15:719–731

    Article  CAS  PubMed  Google Scholar 

  • Park SC, Kwak YM, Song WS, Hong M, Yoon S-I (2017a) Structural basis of effector and operator recognition by the phenolic acid-responsive transcriptional regulator PadR. Nucleic Acids Res 45:13080–13093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park N et al (2017b) Crystal structure of the regulatory domain of AphB from Vibrio vulnificus, a virulence gene regulator. Mol Cells 40:299–306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pearson GDN et al (1990) New attenuated derivatives of Vibrio cholerae. Res Microbiol 141:893–899

    Article  CAS  PubMed  Google Scholar 

  • Privett BR et al (2017) Identification of a small molecule activator for AphB, a LysR-type virulence transcriptional regulator in Vibrio cholerae. Biochemistry 56:3840–3849

    Article  CAS  PubMed  Google Scholar 

  • Provenzano D, Schuhmacher DA, Barker JL, Klose KE (2000) The virulence regulatory protein ToxR mediates enhanced bile resistance in Vibrio cholerae and other pathogenic Vibrio species. Infect Immun 68:1491–1497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rhee JE, Jeong HG, Lee JH, Choi SH (2006) AphB influences acid tolerance of Vibrio vulnificus by activating expression of the positive regulator CadC. J Bacteriol 188:6490–6497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rutherford ST, van Kessel JC, Shao Y, Bassler BL (2011) AphA and LuxR/HapR reciprocally control quorum sensing in vibrios. Genes Dev 25:397–408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sadotra S et al (2021) Structural basis for promoter DNA recognition by the response regulator OmpR. J Struct Biol 213:107638

    Article  CAS  PubMed  Google Scholar 

  • Schlundt A et al (2017) Structure-function analysis of the DNA-binding domain of a transmembrane transcriptional activator. Sci Rep 7:1051–1016

    Article  PubMed  PubMed Central  Google Scholar 

  • Shakhnovich EA, Hung DT, Pierson E, Lee K, Mekalanos JJ (2007) Virstatin inhibits dimerization of the transcriptional activator ToxT. Proc Natl Acad Sci U S A 104:2372–2377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shrestha M, Xiao Y, Robinson H, Schubot FD (2015) Structural analysis of the regulatory domain of ExsA, a key transcriptional regulator of the type three secretion system in Pseudomonas aeruginosa. PLoS One 10:e0136533–e0136517

    Article  PubMed  PubMed Central  Google Scholar 

  • Skorupski K, Taylor RK (1999) A new level in the Vibrio cholerae ToxR virulence cascade: AphA is required for transcriptional activation of the tcpPH operon. Mol Microbiol 31:763–771

    Article  CAS  PubMed  Google Scholar 

  • Soisson SM, MacDougall-Shackleton B, Schleif R, Wolberger C (1997) The 1.6 A crystal structure of the AraC sugar-binding and dimerization domain complexed with D-fucose. J Mol Biol 273:226–237

    Article  CAS  PubMed  Google Scholar 

  • Stutzmann S, Blokesch M (2016) Circulation of a quorum-sensing-impaired variant of Vibrio cholerae strain C6706 masks important phenotypes. mSphere 1

    Google Scholar 

  • Taylor JL et al (2012) The crystal structure of AphB, a virulence gene activator from Vibrio cholerae, reveals residues that influence its response to oxygen and pH. Mol Microbiol 83:457–470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsou AM, Cai T, Liu Z, Zhu J, Kulkarni RV (2009) Regulatory targets of quorum sensing in Vibrio cholerae: evidence for two distinct HapR-binding motifs. Nucleic Acids Res 37:2747–2756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Whitaker WB, Parent MA, Boyd A, Richards GP, Boyd EF (2012) The Vibrio parahaemolyticus ToxRS regulator is required for stress tolerance and colonization in a novel orogastric streptomycin-induced adult murine model. Infect Immun 80:1834–1845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Withey JH, DiRita VJ (2006) The toxbox: specific DNA sequence requirements for activation of Vibrio cholerae virulence genes by ToxT. Mol Microbiol 59:1779–1789

    Article  CAS  PubMed  Google Scholar 

  • Woodbrey AK et al (2017) A new class of inhibitors of the AraC family virulence regulator Vibrio cholerae ToxT. Sci Rep 1–11. https://doi.org/10.1038/srep45011

  • Woodbrey AK, Onyango EO, Kovacikova G, Kull FJ, Gribble GW (2018) A modified ToxT inhibitor reduces Vibrio cholerae virulence in vivo. Biochemistry 57:5609–5615

    Article  CAS  PubMed  Google Scholar 

  • Yang Y, Isberg RR (1997) Transcriptional regulation of the Yersinia pseudotuberculosis pH 6 antigen adhesin by two envelope-associated components. Mol Microbiol 24:499–510

    Article  CAS  PubMed  Google Scholar 

  • Yang M et al (2013) Bile salt-induced intermolecular disulfide bond formation activates Vibrio cholerae virulence. Proc Natl Acad Sci U S A 110:2348–2353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang J et al (2021) Binding site profiles and N-terminal minor groove interactions of the master quorum-sensing regulator LuxR enable flexible control of gene activation and repression. Nucleic Acids Res 49:3274–3293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu J, Mekalanos JJ (2003) Quorum sensing-dependent biofilms enhance colonization in Vibrio cholerae. Dev Cell 5:647–656

    Article  CAS  PubMed  Google Scholar 

  • Zhu J et al (2002) Quorum-sensing regulators control virulence gene expression in Vibrio cholerae. Proc Natl Acad Sci 99:3129–3134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Chemistry Department, Dartmouth College, Hanover, NH, USA

    Charles R. Midgett & F. Jon Kull

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  1. Charles R. Midgett
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  2. F. Jon Kull
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Correspondence to F. Jon Kull .

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  1. Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL, USA

    Salvador Almagro-Moreno

  2. Department of Biology, The City College of New York, New York, NY, USA

    Stefan Pukatzki

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Midgett, C.R., Kull, F.J. (2023). Structural Insights into Regulation of Vibrio Virulence Gene Networks. In: Almagro-Moreno, S., Pukatzki, S. (eds) Vibrio spp. Infections. Advances in Experimental Medicine and Biology, vol 1404. Springer, Cham. https://doi.org/10.1007/978-3-031-22997-8_14

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