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Pharmacology of T2R Mediated Host–Microbe Interactions

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The Pharmacology of Taste

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 275))

Abstract

Bitter taste receptors (T2Rs) belong to the G protein-coupled receptor superfamily. Humans express 25 T2Rs that are known to detect several bitter compounds including bacterial quorum sensing molecules (QSM). Primarily found to be key receptors for bitter sensation T2Rs are known to play an important role in mediating innate immune responses in oral and extraoral tissues. Several studies have led to identification of Gram-negative and Gram-positive bacterial QSMs as agonists for T2Rs in airway epithelial cells and immune cells. However, the pharmacological characterization for many of the QSM–T2R interactions remains poorly defined. In this chapter, we discuss the extraoral roles including localization of T2Rs in extracellular vesicles, molecular pharmacology of QSM–T2R interactions, role of T2Rs in mediating innate immune responses, and some of the challenges in understanding T2R pharmacology.

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References

  • Adler E, Hoon MA, Mueller KL, Chandrashekar J, Ryba NJ et al (2000) A novel family of mammalian taste receptors. Cell 100:693–702

    Article  CAS  PubMed  Google Scholar 

  • Avau B, Rotondo A, Thijs T, Andrews CN, Janssen P et al (2015) Targeting extra-oral bitter taste receptors modulates gastrointestinal motility with effects on satiation. Sci Rep 5:15985

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baker EK, Colley NJ, Zuker CS (1994) The cyclophilin homolog NinaA functions as a chaperone, forming a stable complex in vivo with its protein target rhodopsin. EMBO J 13:4886–4895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barber C, Tang J, Feng J, Pan M, Wilson T et al (1997) A novel regulatory system required for pathogenicity of Xanthomonas campestris is mediated by a small diffusible signal molecule. Mol Microbiol 24:555–566

    Article  CAS  PubMed  Google Scholar 

  • Barham HP, Cooper SE, Anderson CB, Tizzano M, Kingdom TT et al (2013) Solitary chemosensory cells and bitter taste receptor signaling in human sinonasal mucosa. Int Forum Allergy Rhinol 3:450–457

    Article  PubMed  PubMed Central  Google Scholar 

  • Barrett E, Ross R, O’toole P, Fitzgerald G, Stanton C (2012) γ-Aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol 113:411–417

    Article  CAS  PubMed  Google Scholar 

  • Barth C, Jakubczyk D, Kubas A, Anastassacos F, Brenner-Weiss G et al (2012) Interkingdom signaling: integration, conformation, and orientation of N-acyl-L-homoserine lactones in supported lipid bilayers. Langmuir 28:8456–8462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bartoshuk LM (2000) Comparing sensory experiences across individuals: recent psychophysical advances illuminate genetic variation in taste perception. Chem Senses 25:447–460

    Article  CAS  PubMed  Google Scholar 

  • Baumer-Harrison C, Raymond MA, Myers TA 2nd, Sussman KM, Rynberg ST et al (2020) Optogenetic stimulation of type I GAD65(+) cells in taste buds activates gustatory neurons and drives appetitive licking behavior in sodium-depleted mice. J Neurosci 40(41):7795–7810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bebelman MP, Crudden C, Pegtel DM, Smit MJ (2020) The convergence of extracellular vesicle and GPCR biology. Trends Pharmacol Sci 41:627–640

    Article  CAS  PubMed  Google Scholar 

  • Bhargava N, Sharma P, Capalash N (2012) N-acyl homoserine lactone mediated interspecies interactions between A. baumannii and P. aeruginosa. Biofouling 28:813–822

    Article  CAS  PubMed  Google Scholar 

  • Blanchard N, Lankar D, Faure F, Regnault A, Dumont C et al (2002) TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/zeta complex. J Immunol 168:3235–3241

    Article  CAS  PubMed  Google Scholar 

  • Brandenburg KS, Rodriguez KJ, McAnulty JF, Murphy CJ, Abbott NL et al (2013) Tryptophan inhibits biofilm formation by Pseudomonas aeruginosa. Antimicrob Agents Chemother 57:1921–1925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Braschi B, Denny P, Gray K, Jones T, Seal R et al (2019) Genenames.org: the HGNC and VGNC resources in 2019. Nucleic Acids Res 47:D786–D792

    Article  CAS  PubMed  Google Scholar 

  • Bredenbruch F, Nimtz M, Wray V, Morr M, Muller R et al (2005) Biosynthetic pathway of Pseudomonas aeruginosa 4-hydroxy-2-alkylquinolines. J Bacteriol 187:3630–3635

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cancello R, Micheletto G, Meta D, Lavagno R, Bevilacqua E et al (2020) Expanding the role of bitter taste receptor in extra oral tissues: TAS2R38 is expressed in human adipocytes. Adipocytes 9:7–15

    Article  CAS  Google Scholar 

  • Carey RM, Workman AD, Hatten KM, Siebert AP, Brooks SG et al (2017a) Denatonium-induced sinonasal bacterial killing may play a role in chronic rhinosinusitis outcomes. Int Forum Allergy Rhinol 7:699–704

    Article  PubMed  PubMed Central  Google Scholar 

  • Carey RM, Workman AD, Yan CH, Chen B, Adappa ND et al (2017b) Sinonasal T2R-mediated nitric oxide production in response to Bacillus cereus. Am J Rhinol Allergy 31:211–215

    Article  PubMed  PubMed Central  Google Scholar 

  • Chandrashekar J, Mueller KL, Hoon MA, Adler E, Feng L et al (2000) T2Rs function as bitter taste receptors. Cell 100:703–711

    Article  CAS  PubMed  Google Scholar 

  • Chen J, Larson ED, Anderson CB, Agarwal P, Frank DN et al (2019) Expression of bitter taste receptors and solitary chemosensory cell markers in the human sinonasal cavity. Chem Senses 44:483–495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cvitkovitch D (2001) Genetic competence and transformation in oral streptococci. Crit Rev Oral Biol Med 12:217–243

    Article  CAS  PubMed  Google Scholar 

  • Delcayre A, Estelles A, Sperinde J, Roulon T, Paz P et al (2005) Exosome display technology: applications to the development of new diagnostics and therapeutics. Blood Cells Mol Dis 35:158–168

    Article  CAS  PubMed  Google Scholar 

  • DeWire SM, Ahn S, Lefkowitz RJ, Shenoy SK (2007) Beta-arrestins and cell signaling. Annu Rev Physiol 69:483–510

    Article  CAS  PubMed  Google Scholar 

  • Diggle SP, Cornelis P, Williams P, Camara M (2006) 4-quinolone signalling in Pseudomonas aeruginosa: old molecules, new perspectives. Int J Med Microbiol 296:83–91

    Article  CAS  PubMed  Google Scholar 

  • DiPatrizio NV (2014) Is fat taste ready for primetime? Physiol Behav 136:145–154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dwyer ND, Troemel ER, Sengupta P, Bargmann CI (1998) Odorant receptor localization to olfactory cilia is mediated by ODR-4, a novel membrane-associated protein. Cell 93:455–466

    Article  CAS  PubMed  Google Scholar 

  • Estelles A, Sperinde J, Roulon T, Aguilar B, Bonner C et al (2007) Exosome nanovesicles displaying G protein-coupled receptors for drug discovery. Int J Nanomedicine 2:751–760

    CAS  PubMed  PubMed Central  Google Scholar 

  • Farquhar DR, Kovatch KJ, Palmer JN, Shofer FS, Adappa ND et al (2015) Phenylthiocarbamide taste sensitivity is associated with sinonasal symptoms in healthy adults. Int Forum Allergy Rhinol 5:111–118

    Article  PubMed  Google Scholar 

  • Flavier AB, Clough SJ, Schell MA, Denny TP (1997) Identification of 3-hydroxypalmitic acid methyl ester as a novel autoregulator controlling virulence in Ralstonia solanacearum. Mol Microbiol 26:251–259

    Article  CAS  PubMed  Google Scholar 

  • Freund JR, Mansfield CJ, Doghramji LJ, Adappa ND, Palmer JN et al (2018) Activation of airway epithelial bitter taste receptors by Pseudomonas aeruginosa quinolones modulates calcium, cyclic-AMP, and nitric oxide signaling. J Biol Chem 293:9824–9840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gaida MM, Dapunt U, Hänsch GM (2016a) Sensing developing biofilms: the bitter receptor T2R38 on myeloid cells. Pathog Dis 74(3):ftw004

    Article  PubMed  PubMed Central  Google Scholar 

  • Gaida MM, Mayer C, Dapunt U, Stegmaier S, Schirmacher P et al (2016b) Expression of the bitter receptor T2R38 in pancreatic cancer: localization in lipid droplets and activation by a bacteria-derived quorum-sensing molecule. Oncotarget 7:12623–12632

    Article  PubMed  PubMed Central  Google Scholar 

  • Gallo S, Grossi S, Montrasio G, Binelli G, Cinquetti R et al (2016) TAS2R38 taste receptor gene and chronic rhinosinusitis: new data from an Italian population. BMC Med Genet 17:54

    Article  PubMed  PubMed Central  Google Scholar 

  • Gilbertson TA, Avenet P, Kinnamon SC, Roper SD (1992) Proton currents through amiloride-sensitive Na channels in hamster taste cells. Role in acid transduction. J Gen Physiol 100:803–824

    Article  CAS  PubMed  Google Scholar 

  • González JF, Venturi V (2013) A novel widespread interkingdom signaling circuit. Trends Plant Sci 18:167–174

    Article  PubMed  Google Scholar 

  • Gopallawa I, Freund JR, Lee RJ (2020) Bitter taste receptors stimulate phagocytosis in human macrophages through calcium, nitric oxide, and cyclic-GMP signaling. Cell Mol Life Sci. https://doi.org/10.1007/s00018-020-03494-y

  • Hansch GM, Prior B, Brenner-Weiss G, Obst U, Overhage J (2014) The Pseudomonas quinolone signal (PQS) stimulates chemotaxis of polymorphonuclear neutrophils. J Appl Biomater Funct Mater 12:21–26

    PubMed  Google Scholar 

  • Hariri BM, McMahon DB, Chen B, Freund JR, Mansfield CJ et al (2017) Flavones modulate respiratory epithelial innate immunity: anti-inflammatory effects and activation of the T2R14 receptor. J Biol Chem 292:8484–8497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Håvarstein LS, Coomaraswamy G, Morrison DA (1995) An unmodified heptadecapeptide pheromone induces competence for genetic transformation in Streptococcus pneumoniae. Proc Natl Acad Sci U S A 92:11140–11144

    Article  PubMed  PubMed Central  Google Scholar 

  • He W, Danilova V, Zou S, Hellekant G, Max M et al (2002) Partial rescue of taste responses of alpha-gustducin null mice by transgenic expression of alpha-transducin. Chem Senses 27:719–727

    Article  CAS  PubMed  Google Scholar 

  • Heck GL, Mierson S, DeSimone JA (1984) Salt taste transduction occurs through an amiloride-sensitive sodium transport pathway. Science 223:403–405

    Article  CAS  PubMed  Google Scholar 

  • Heeb S, Fletcher MP, Chhabra SR, Diggle SP, Williams P et al (2011) Quinolones: from antibiotics to autoinducers. FEMS Microbiol Rev 35:247–274

    Article  CAS  PubMed  Google Scholar 

  • Holden MT, Ram Chhabra S, De Nys R, Stead P, Bainton NJ et al (1999) Quorum-sensing cross talk: isolation and chemical characterization of cyclic dipeptides from Pseudomonas aeruginosa and other gram-negative bacteria. Mol Microbiol 33:1254–1266

    Article  CAS  PubMed  Google Scholar 

  • Hossain MS, Biswas I (2012) An extracelluar protease, SepM, generates functional competence-stimulating peptide in Streptococcus mutans UA159. J Bacteriol 194:5886–5896

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Isberg V, Mordalski S, Munk C, Rataj K, Harpsoe K et al (2017) GPCRdb: an information system for G protein-coupled receptors. Nucleic Acids Res 45:2936

    Article  CAS  PubMed  Google Scholar 

  • Itoigawa A, Hayakawa T, Suzuki-Hashido N, Imai H (2019) A natural point mutation in the bitter taste receptor TAS2R16 causes inverse agonism of arbutin in lemur gustation. Proc Biol Sci 286:20190884

    CAS  PubMed  PubMed Central  Google Scholar 

  • Iven J, Biesiekierski JR, Zhao D, Deloose E, O’Daly OG et al (2019) Intragastric quinine administration decreases hedonic eating in healthy women through peptide-mediated gut-brain signaling mechanisms. Nutr Neurosci 22:850–862

    Article  CAS  PubMed  Google Scholar 

  • Jaggupilli A, Howard R, Upadhyaya JD, Bhullar RP, Chelikani P (2016) Bitter taste receptors: novel insights into the biochemistry and pharmacology. Int J Biochem Cell Biol 77:184–196

    Article  CAS  PubMed  Google Scholar 

  • Jaggupilli A, Singh N, Upadhyaya J, Sikarwar AS, Arakawa M et al (2017) Analysis of the expression of human bitter taste receptors in extraoral tissues. Mol Cell Biochem 426:137–147

    Article  CAS  PubMed  Google Scholar 

  • Jaggupilli A, Singh N, Jesus VC, Duan K, Chelikani P (2018) Characterization of the binding sites for bacterial acyl homoserine lactones (AHLs) on human bitter taste receptors (T2Rs). ACS Infect Dis 4:1146–1156

    Article  CAS  PubMed  Google Scholar 

  • Jaggupilli A, Singh N, De Jesus VC, Gounni MS, Dhanaraj P et al (2019) Chemosensory bitter taste receptors (T2Rs) are activated by multiple antibiotics. FASEB J 33:501–517

    Article  CAS  PubMed  Google Scholar 

  • Kahn R, Mossberg M, Ståhl AL, Johansson K, Lopatko Lindman I et al (2017) Microvesicle transfer of kinin B1-receptors is a novel inflammatory mechanism in vasculitis. Kidney Int 91:96–105

    Article  CAS  PubMed  Google Scholar 

  • Karlsson T, Turkina MV, Yakymenko O, Magnusson K-E, Vikström E (2012) The Pseudomonas aeruginosa N-acylhomoserine lactone quorum sensing molecules target IQGAP1 and modulate epithelial cell migration. PLoS Pathog 8:e1002953

    Article  PubMed  PubMed Central  Google Scholar 

  • Kim K, Kim YU, Koh BH, Hwang SS, Kim S-H et al (2010) HHQ and PQS, two Pseudomonas aeruginosa quorum-sensing molecules, down-regulate the innate immune responses through the nuclear factor-kappaB pathway. Immunology 129:578–588

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim KS, Egan JM, Jang HJ (2014) Denatonium induces secretion of glucagon-like peptide-1 through activation of bitter taste receptor pathways. Diabetologia 57:2117–2125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim D, Pauer SH, Yong HM, An SS, Liggett SB (2016) beta2-adrenergic receptors chaperone trapped bitter taste receptor 14 to the cell surface as a heterodimer and exert unidirectional desensitization of taste receptor function. J Biol Chem 291:17616–17628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kinnamon SC, Cummings TA (1992) Chemosensory transduction mechanisms in taste. Annu Rev Physiol 54:715–731

    Article  CAS  PubMed  Google Scholar 

  • Kleerebezem M, Quadri LE, Kuipers OP, de Vos WM (1997) Quorum sensing by peptide pheromones and two-component signal-transduction systems in gram-positive bacteria. Mol Microbiol 24:895–904

    Article  CAS  PubMed  Google Scholar 

  • Kravchenko VV, Kaufmann GF, Mathison JC, Scott DA, Katz AZ et al (2006) N-(3-Oxo-acyl)homoserine lactones signal cell activation through a mechanism distinct from the canonical pathogen-associated molecular pattern recognition receptor pathways. J Biol Chem 281:28822–28830

    Article  CAS  PubMed  Google Scholar 

  • Kravchenko VV, Kaufmann GF, Mathison JC, Scott DA, Katz AZ et al (2008) Modulation of gene expression via disruption of NF-κb signaling by a bacterial small molecule. Science 321:259–263

    Article  CAS  PubMed  Google Scholar 

  • Kwon SH, Liu KD, Mostov KE (2014) Intercellular transfer of GPRC5B via exosomes drives HGF-mediated outward growth. Curr Biol 24:199–204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lam H, Oh D-C, Cava F, Takacs CN, Clardy J et al (2009) D-amino acids govern stationary phase cell wall remodeling in bacteria. Science 325:1552–1555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Latorre R, Huynh J, Mazzoni M, Gupta A, Bonora E et al (2016) Expression of the bitter taste receptor, T2R38, in enteroendocrine cells of the colonic mucosa of overweight/obese vs. lean subjects. PLoS One 11:e0147468

    Article  PubMed  PubMed Central  Google Scholar 

  • Laugerette F, Passilly-Degrace P, Patris B, Niot I, Febbraio M et al (2005) CD36 involvement in orosensory detection of dietary lipids, spontaneous fat preference, and digestive secretions. J Clin Invest 115:3177–3184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lazazzera BA, Grossman AD (1998) The ins and outs of peptide signaling. Trends Microbiol 6:288–294

    Article  CAS  PubMed  Google Scholar 

  • Lee J, Zhang L (2015) The hierarchy quorum sensing network in Pseudomonas aeruginosa. Protein Cell 6:26–41

    Article  CAS  PubMed  Google Scholar 

  • Lee RJ, Xiong G, Kofonow JM, Chen B, Lysenko A et al (2012) T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection. J Clin Investig 122:4145–4159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee RJ, Kofonow JM, Rosen PL, Siebert AP, Chen B et al (2014) Bitter and sweet taste receptors regulate human upper respiratory innate immunity. J Clin Invest 124:1393–1405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee RJ, Hariri BM, McMahon DB, Chen B, Doghramji L et al (2017) Bacterial class d-amino acids suppress sinonasal innate immunity through sweet taste receptors in solitary chemosensory cells. Sci Signal 10:eaam7703

    Article  PubMed  PubMed Central  Google Scholar 

  • Lepine F, Milot S, Deziel E, He J, Rahme LG (2004) Electrospray/mass spectrometric identification and analysis of 4-hydroxy-2-alkylquinolines (HAQs) produced by Pseudomonas aeruginosa. J Am Soc Mass Spectrom 15:862–869

    Article  CAS  PubMed  Google Scholar 

  • Lewandowski BC, Sukumaran SK, Margolskee RF, Bachmanov AA (2016) Amiloride-insensitive salt taste is mediated by two populations of type III taste cells with distinct transduction mechanisms. J Neurosci 36:1942–1953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Z, Nair SK (2012) Quorum sensing: how bacteria can coordinate activity and synchronize their response to external signals? Protein Sci 21:1403–1417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li H, Li X, Wang Z, Fu Y, Ai Q et al (2015) Autoinducer-2 regulates Pseudomonas aeruginosa PAO1 biofilm formation and virulence production in a dose-dependent manner. BMC Microbiol 15:192–192

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu X, Yu Y, Qin D, Song Z, Huang Z et al (2020) Expression analysis of taste receptor genes (T1R1, T1R3, and T2R4) in response to bacterial, viral and parasitic infection in rainbow trout, Oncorhynchus mykiss. Fish Shellfish Immunol 101:176–185

    Article  CAS  PubMed  Google Scholar 

  • Lossow K, Hubner S, Roudnitzky N, Slack JP, Pollastro F et al (2016) Comprehensive analysis of mouse bitter taste receptors reveals different molecular receptive ranges for orthologous receptors in mice and humans. J Biol Chem 291:15358–15377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lyte M, Ernst S (1993) Alpha and beta adrenergic receptor involvement in catecholamine-induced growth of gram-negative bacteria. Biochem Biophys Res Commun 190:447–452

    Article  CAS  PubMed  Google Scholar 

  • Martin LTP, Nachtigal MW, Selman T, Nguyen E, Salsman J et al (2019) Bitter taste receptors are expressed in human epithelial ovarian and prostate cancers cells and noscapine stimulation impacts cell survival. Mol Cell Biochem 454:203–214

    Article  CAS  PubMed  Google Scholar 

  • Maurer S, Wabnitz GH, Kahle NA, Stegmaier S, Prior B et al (2015) Tasting Pseudomonas aeruginosa biofilms: human neutrophils express the bitter receptor T2R38 as sensor for the quorum sensing molecule N-(3-oxododecanoyl)-l-homoserine lactone. Front Immunol 6:369

    Article  PubMed  PubMed Central  Google Scholar 

  • Medapati MR, Singh A, Korupally RR, Henderson D, Klonisch T et al (2017) Characterization of GPCRs in extracellular vesicle (EV). Methods Cell Biol 142:119–132

    Article  CAS  PubMed  Google Scholar 

  • Medapati MR, Singh N, Chelikani P (2018) The role of bitter taste receptors in oral innate immunity. In: IADR/PER 96th general session, London

    Google Scholar 

  • Meyerhof W, Batram C, Kuhn C, Brockhoff A, Chudoba E et al (2010) The molecular receptive ranges of human TAS2R bitter taste receptors. Chem Senses 35:157–170

    Article  CAS  PubMed  Google Scholar 

  • Milioni C, Martínez B, Degl’Innocenti S, Turchi B, Fratini F et al (2015) A novel bacteriocin produced by Lactobacillus plantarum LpU4 as a valuable candidate for biopreservation in artisanal raw milk cheese. Dairy Sci Technol 95:479–494

    Article  CAS  Google Scholar 

  • Miller EL, Kjos M, Abrudan MI, Roberts IS, Veening J-W et al (2018) Eavesdropping and crosstalk between secreted quorum sensing peptide signals that regulate bacteriocin production in Streptococcus pneumoniae. ISME J 12:2363–2375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Montgomery ST, Mall MA, Kicic A, Stick SM (2017) Hypoxia and sterile inflammation in cystic fibrosis airways: mechanisms and potential therapies. Eur Respir J 49:1600903

    Article  PubMed  Google Scholar 

  • Ozeck M, Brust P, Xu H, Servant G (2004) Receptors for bitter, sweet and umami taste couple to inhibitory G protein signaling pathways. Eur J Pharmacol 489:139–149

    Article  CAS  PubMed  Google Scholar 

  • Pacheco AR, Sperandio V (2009) Inter-kingdom signaling: chemical language between bacteria and host. Curr Opin Microbiol 12:192–198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pándy-Szekeres G, Munk C, Tsonkov TM, Mordalski S, Harpsøe K et al (2018) GPCRdb in 2018: adding GPCR structure models and ligands. Nucleic Acids Res 46:D440–d446

    Article  PubMed  Google Scholar 

  • Park J, Kim KS, Kim KH, Lee IS, Jeong HS et al (2015) GLP-1 secretion is stimulated by 1,10-phenanthroline via colocalized T2R5 signal transduction in human enteroendocrine L cell. Biochem Biophys Res Commun 468:306–311

    Article  CAS  PubMed  Google Scholar 

  • Pironti G, Strachan RT, Abraham D, Mon-Wei Yu S, Chen M et al (2015) Circulating exosomes induced by cardiac pressure overload contain functional angiotensin II type 1 receptors. Circulation 131:2120–2130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pydi SP, Bhullar RP, Chelikani P (2012) Constitutively active mutant gives novel insights into the mechanism of bitter taste receptor activation. J Neurochem 122:537–544

    Article  CAS  PubMed  Google Scholar 

  • Pydi SP, Chakraborty R, Bhullar RP, Chelikani P (2013) Role of rhodopsin N-terminus in structure and function of rhodopsin-bitter taste receptor chimeras. Biochem Biophys Res Commun 430:179–182

    Article  CAS  PubMed  Google Scholar 

  • Pydi SP, Bhullar RP, Chelikani P (2014a) Constitutive activity of bitter taste receptors (T2Rs). Adv Pharmacol 70:303–326

    Article  CAS  PubMed  Google Scholar 

  • Pydi SP, Sobotkiewicz T, Billakanti R, Bhullar RP, Loewen MC et al (2014b) Amino acid derivatives as bitter taste receptor (T2R) blockers. J Biol Chem 289:25054–25066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pydi SP, Jaggupilli A, Nelson KM, Abrams SR, Bhullar RP et al (2015) Abscisic acid acts as a blocker of the bitter taste G protein-coupled receptor T2R4. Biochemistry 54:2622–2631

    Article  CAS  PubMed  Google Scholar 

  • Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV et al (1996) B lymphocytes secrete antigen-presenting vesicles. J Exp Med 183:1161–1172

    Article  CAS  PubMed  Google Scholar 

  • Roland WS, Gouka RJ, Gruppen H, Driesse M, van Buren L et al (2014) 6-Methoxyflavanones as bitter taste receptor blockers for hTAS2R39. PLoS One 9:e94451

    Article  PubMed  PubMed Central  Google Scholar 

  • Rom DI, Christensen JM, Alvarado R, Sacks R, Harvey RJ (2017) The impact of bitter taste receptor genetics on culturable bacteria in chronic rhinosinusitis. Rhinology 55:90–94

    Article  CAS  PubMed  Google Scholar 

  • Sainz E, Cavenagh MM, Gutierrez J, Battey JF, Northup JK et al (2007) Functional characterization of human bitter taste receptors. Biochem J 403:537–543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salvadori G, Junges R, Morrison DA, Petersen FC (2019) Competence in Streptococcus pneumoniae and close commensal relatives: mechanisms and implications. Front Cell Infect Microbiol 9

    Google Scholar 

  • Sarkar S, Pires MM (2015) D-amino acids do not inhibit biofilm formation in Staphylococcus aureus. PLoS One 10:e0117613

    Article  PubMed  PubMed Central  Google Scholar 

  • Saunders CJ, Christensen M, Finger TE, Tizzano M (2014) Cholinergic neurotransmission links solitary chemosensory cells to nasal inflammation. Proc Natl Acad Sci U S A 111:6075–6080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schertzer JW, Brown SA, Whiteley M (2010) Oxygen levels rapidly modulate Pseudomonas aeruginosa social behaviours via substrate limitation of PqsH. Mol Microbiol 77:1527–1538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schneider KB, Palmer TM, Grossman AD (2002) Characterization of comQ and comX, two genes required for production of ComX pheromone in Bacillus subtilis. J Bacteriol 184:410–419

    Article  CAS  PubMed Central  Google Scholar 

  • Schwarzer C, Wong S, Shi J, Matthes E, Illek B et al (2010) Pseudomonas aeruginosa homoserine lactone activates store-operated cAMP and cystic fibrosis transmembrane regulator-dependent Cl− secretion by human airway epithelia. J Biol Chem 285:34850–34863

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seo Y, Kim YS, Lee KE, Park TH, Kim Y (2017) Anti-cancer stemness and anti-invasive activity of bitter taste receptors, TAS2R8 and TAS2R10, in human neuroblastoma cells. PLoS One 12:e0176851

    Article  PubMed  PubMed Central  Google Scholar 

  • Shah AS, Ben-Shahar Y, Moninger TO, Kline JN, Welsh MJ (2009) Motile cilia of human airway epithelia are chemosensory. Science 325:1131–1134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shaik FA, Singh N, Arakawa M, Duan K, Bhullar RP et al (2016) Bitter taste receptors: extraoral roles in pathophysiology. Int J Biochem Cell Biol 77:197–204

    Article  CAS  PubMed  Google Scholar 

  • Shaik FA, Medapati MR, Chelikani P (2019) Cholesterol modulates the signaling of chemosensory bitter taste receptor T2R14 in human airway cells. Am J Physiol Lung Cell Mol Physiol 316:L45–L57

    Article  CAS  PubMed  Google Scholar 

  • Shiner EK, Rumbaugh KP, Williams SC (2005) Interkingdom signaling: deciphering the language of acyl homoserine lactones. FEMS Microbiol Rev 29:935–947

    Article  CAS  PubMed  Google Scholar 

  • Shiner E, Terentyev D, Bryan A, Sennoune S, Martinez-Zaguilan R et al (2006) Pseudomonas aeruginosa autoinducer modulates host cell responses through calcium signalling. Cell Microbiol 8:1601–1610

    Article  CAS  PubMed  Google Scholar 

  • Simhadri VR, Reiners KS, Hansen HP, Topolar D, Simhadri VL et al (2008) Dendritic cells release HLA-B-associated transcript-3 positive exosomes to regulate natural killer function. PLoS One 3:e3377

    Article  PubMed  PubMed Central  Google Scholar 

  • Singh N, Vrontakis M, Parkinson F, Chelikani P (2011) Functional bitter taste receptors are expressed in brain cells. Biochem Biophys Res Commun 406:146–151

    Article  CAS  PubMed  Google Scholar 

  • Singh N, Shaik FA, Myal Y, Chelikani P (2020) Chemosensory bitter taste receptors T2R4 and T2R14 activation attenuates proliferation and migration of breast cancer cells. Mol Cell Biochem 465:199–214

    Article  CAS  PubMed  Google Scholar 

  • Sturme MH, Kleerebezem M, Nakayama J, Akkermans AD, Vaughan EE et al (2002) Cell to cell communication by autoinducing peptides in gram-positive bacteria. Antonie Van Leeuwenhoek 81:233–243

    Article  CAS  PubMed  Google Scholar 

  • Taga ME, Bassler BL (2003) Chemical communication among bacteria. Proc Natl Acad Sci 100:14549–14554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Taher S, Borja Y, Cabanela L, Costers VJ, Carson-Marino M et al (2019) Cholecystokinin, gastrin, cholecystokinin/gastrin receptors, and bitter taste receptor TAS2R14: trophoblast expression and signaling. Am J Physiol Regul Integr Comp Physiol 316:R628–r639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Telford G, Wheeler D, Williams P, Tomkins P, Appleby P et al (1998) The Pseudomonas aeruginosa quorum-sensing signal moleculen-(3-oxododecanoyl)-l-homoserine lactone has immunomodulatory activity. Infect Immun 66:36–42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thoendel M, Kavanaugh JS, Flack CE, Horswill AR (2011) Peptide signaling in the staphylococci. Chem Rev 111:117–151

    Article  CAS  PubMed  Google Scholar 

  • Tizzano M, Gulbransen BD, Vandenbeuch A, Clapp TR, Herman JP et al (2010) Nasal chemosensory cells use bitter taste signaling to detect irritants and bacterial signals. Proc Natl Acad Sci 107:3210–3215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trams EG, Lauter CJ, Salem N Jr, Heine U (1981) Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim Biophys Acta 645:63–70

    Article  CAS  PubMed  Google Scholar 

  • Tran HTT, Herz C, Ruf P, Stetter R, Lamy E (2018) Human T2R38 bitter taste receptor expression in resting and activated lymphocytes. Front Immunol 9:2949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tu YH, Cooper AJ, Teng B, Chang RB, Artiga DJ et al (2018) An evolutionarily conserved gene family encodes proton-selective ion channels. Science 359:1047–1050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Turnbull AR, Murphy R, Behrends V, Lund-Palau H, Simbo A et al (2018) Impact of T2R38 receptor polymorphisms on Pseudomonas aeruginosa infection in cystic fibrosis. Am J Respir Crit Care Med 197:1635–1638

    Article  PubMed  PubMed Central  Google Scholar 

  • Ueda T, Ugawa S, Yamamura H, Imaizumi Y, Shimada S (2003) Functional interaction between T2R taste receptors and G-protein alpha subunits expressed in taste receptor cells. J Neurosci 23:7376–7380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Upadhyaya JD, Chakraborty R, Shaik FA, Jaggupilli A, Bhullar RP et al (2016) The pharmacochaperone activity of quinine on bitter taste receptors. PLoS One 11:e0156347

    Article  PubMed  PubMed Central  Google Scholar 

  • Verbeke F, De Craemer S, Debunne N, Janssens Y, Wynendaele E et al (2017) Peptides as quorum sensing molecules: measurement techniques and obtained levels in vitro and in vivo. Front Neurosci 11

    Google Scholar 

  • Verbeurgt C, Veithen A, Carlot S, Tarabichi M, Dumont JE et al (2017) The human bitter taste receptor T2R38 is broadly tuned for bacterial compounds. PLoS One 12:e0181302

    Article  PubMed  PubMed Central  Google Scholar 

  • Wade DS, Calfee MW, Rocha ER, Ling EA, Engstrom E et al (2005) Regulation of pseudomonas quinolone signal synthesis in Pseudomonas aeruginosa. J Bacteriol 187:4372–4380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Q, Liszt KI, Deloose E, Canovai E, Thijs T et al (2019) Obesity alters adrenergic and chemosensory signaling pathways that regulate ghrelin secretion in the human gut. FASEB J 33:4907–4920

    Article  CAS  PubMed  Google Scholar 

  • Wei H, Ahn S, Shenoy SK, Karnik SS, Hunyady L et al (2003) Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2. Proc Natl Acad Sci U S A 100:10782–10787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wong GT, Gannon KS, Margolskee RF (1996) Transduction of bitter and sweet taste by gustducin. Nature 381:796–800

    Article  CAS  PubMed  Google Scholar 

  • Woo JA, Castano M, Goss A, Kim D, Lewandowski EM et al (2019) Differential long-term regulation of TAS2R14 by structurally distinct agonists. FASEB J 33:12213–12225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Workman AD, Maina IW, Brooks SG, Kohanski MA, Cowart BJ et al (2018) The role of quinine-responsive taste receptor family 2 in airway immune defense and chronic Rhinosinusitis. Front Immunol 9:624

    Article  PubMed  PubMed Central  Google Scholar 

  • Xu J, Cao J, Iguchi N, Riethmacher D, Huang L (2013) Functional characterization of bitter-taste receptors expressed in mammalian testis. Mol Hum Reprod 19:17–28

    Article  PubMed  Google Scholar 

  • Yang Y, Koirala B, Sanchez LA, Phillips NR, Hamry SR et al (2017) Structure-activity relationships of the competence stimulating peptides (CSPs) in Streptococcus pneumoniae reveal motifs critical for intra-group and cross-group ComD receptor activation. ACS Chem Biol 12:1141–1151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang C, Alashi AM, Singh N, Liu K, Chelikani P et al (2018) Beef protein-derived peptides as bitter taste receptor T2R4 blockers. J Agric Food Chem 66:4902–4912

    Article  CAS  PubMed  Google Scholar 

  • Zheng X, Tizzano M, Redding K, He J, Peng X et al (2019) Gingival solitary chemosensory cells are immune sentinels for periodontitis. Nat Commun 10:4496

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The work in this review was supported by operating grants from the Natural Sciences and Engineering Research Council of Canada (NSERC), Cystic Fibrosis Canada, and the Canadian Institute of Health Research (CIHR) to P.C. M.R.M. is supported by a doctoral fellowship from Research Manitoba/Children’s Hospital Research Institute of Manitoba, University of Manitoba Graduate Fellowship/MITACS award. A.Y.B is supported by a postdoctoral fellowship from Research Manitoba/Children’s Hospital Research Institute of Manitoba.

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  1. Manitoba Chemosensory Biology Research Group, Department of Oral Biology, Dr. Gerald Niznick College of Dentistry, University of Manitoba, Winnipeg, MB, Canada

    Manoj Reddy Medapati, Anjali Y. Bhagirath, Nisha Singh & Prashen Chelikani

  2. Children’s Hospital Research Institute of Manitoba, Winnipeg, MB, Canada

    Manoj Reddy Medapati, Anjali Y. Bhagirath, Nisha Singh & Prashen Chelikani

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  1. Manoj Reddy Medapati
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  2. Anjali Y. Bhagirath
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  3. Nisha Singh
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Correspondence to Prashen Chelikani .

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    R. Kyle Palmer

  2. Research and Development, Firmenich, Inc., San Diego, CA, USA

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Medapati, M.R., Bhagirath, A.Y., Singh, N., Chelikani, P. (2021). Pharmacology of T2R Mediated Host–Microbe Interactions. In: Palmer, R.K., Servant, G. (eds) The Pharmacology of Taste . Handbook of Experimental Pharmacology, vol 275. Springer, Cham. https://doi.org/10.1007/164_2021_435

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