Chemosensory bitter taste receptors (T2Rs) are activated by multiple antibiotics

FASEB Journal

Volumn 33, Issue 1, 2019, Pages 501-517

  Jaggupilli, Appalaraju ^a   Singh, Nisha ^a   De Jesus, Vivianne Cruz ^a   Gounni, Mohamed Soussi ^a   Dhanaraj, Premnath ^a   Chelikani, Prashen ^a  

^a UNIVERSITY OF MANITOBA   (Canada)

Author keywords

Cystic fibrosis; GPCR; Levofloxacin; Structure function; Tobramycin

Indexed keywords

AMINO ACID; ANTIBIOTIC AGENT; AZITHROMYCIN; BITTER TASTE RECEPTOR; BITTER TASTE RECEPTOR T214; BITTER TASTE RECEPTOR T2R1; BITTER TASTE RECEPTOR T2R20; BITTER TASTE RECEPTOR T2R4; CAFFEINE; CIPROFLOXACIN; CROMOGLYCATE DISODIUM; DEXTROMETHORPHAN; DIPHENHYDRAMINE; ERYTHROMYCIN; G PROTEIN COUPLED RECEPTOR; LEVOFLOXACIN; QUININE; TOBRAMYCIN; UNCLASSIFIED DRUG; ANTIINFECTIVE AGENT; CALCIUM; TASTE RECEPTORS, TYPE 2;

AIRWAY; ARTICLE; BITTER TASTE; CELL ASSAY; CONTROLLED STUDY; DRUG BINDING SITE; HOST CELL; HUMAN; HUMAN CELL; MOLECULAR DOCKING; MOLECULAR MODEL; MUTATIONAL ANALYSIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; RECEPTOR BINDING; RECEPTOR UPREGULATION; SENSORY ANALYSIS; SITE DIRECTED MUTAGENESIS; TASTE BUD; AMINO ACID SEQUENCE; DRUG EFFECT; GENE EXPRESSION REGULATION; GENETICS; HEK293 CELL LINE; METABOLISM; MUTATION; PHYSIOLOGY; PROTEIN SECONDARY STRUCTURE; TASTE;

AMINO ACID SEQUENCE; ANTI-BACTERIAL AGENTS; CALCIUM; GENE EXPRESSION REGULATION; HEK293 CELLS; HUMANS; MODELS, MOLECULAR; MUTAGENESIS, SITE-DIRECTED; MUTATION; PROTEIN STRUCTURE, SECONDARY; RECEPTORS, G-PROTEIN-COUPLED; TASTE;

EID: 85059234847     PISSN: 08926638     EISSN: 15306860     Source Type: Journal    
DOI: 10.1096/fj.201800521RR     Document Type: Article

References (62)

1. Adler, E., Hoon, M. A., Mueller, K. L., Chandrashekar, J., Ryba, N. J., and Zuker, C. S. (2000) A novel family of mammalian taste receptors. Cell 100, 693-702
2. Munk, C., Isberg, V., Mordalski, S., Harpsøe, K., Rataj, K., Hauser, A. S., Kolb, P., Bojarski, A. J., Vriend, G., and Gloriam, D. E. (2016) GPCRdb: the G protein-coupled receptor database-an introduction. Br. J. Pharmacol. 173, 2195-2207
3. Jaggupilli, A., Howard, R., Upadhyaya, J. D., Bhullar, R. P., and Chelikani, P. (2016) Bitter taste receptors: novel insights into the biochemistry and pharmacology. Int. J. Biochem. Cell Biol. 77, 184-196
4. Di Pizio, A., Levit, A., Slutzki, M., Behrens, M., Karaman, R., and Niv, M. Y. (2016) Comparing Class A GPCRs to bitter taste receptors: structural motifs, ligand interactions and agonist-to-antagonist ratios. Methods Cell Biol. 132, 401-427
5. Pydi, S. P., Upadhyaya, J., Singh, N., Pal Bhullar, R., and Chelikani, P. (2012) Recent advances in structure and function studies on human bitter taste receptors. Curr. Protein Pept. Sci. 13, 501-508
6. Shaik, F. A., Singh, N., Arakawa, M., Duan, K., Bhullar, R. P., and Chelikani, P. (2016) Bitter taste receptors: extraoral roles in pathophysiology. Int. J. Biochem. Cell Biol. 77, 197-204
7. Lu, P., Zhang, C. H., Lifshitz, L. M., and ZhuGe, R. (2017) Extraoral bitter taste receptors in health and disease. J. Gen. Physiol. 149, 181-197
8. Avau, B., and Depoortere, I. (2016) The bitter truth about bitter taste receptors: beyond sensing bitter in the oral cavity. Acta Physiol. (Oxf.) 216, 407-420
9. Jaggupilli, A., Singh, N., Upadhyaya, J., Sikarwar, A. S., Arakawa, M., Dakshinamurti, S., Bhullar, R. P., Duan, K., and Chelikani, P. (2017) Analysisofthe expression of human bitter taste receptorsin extraoral tissues. Mol. Cell. Biochem. 426, 137-147
10. Lee, R. J., and Cohen, N. A. (2015) Taste receptors in innate immunity. Cell. Mol. Life Sci. 72, 217-236
11. Wu, S. V., Rozengurt, N., Yang, M., Young, S. H., Sinnett-Smith, J., and Rozengurt, E. (2002) Expression of bitter taste receptors of the T2R family in the gastrointestinal tract and enteroendocrine STC-1 cells. Proc. Natl. Acad. Sci. USA 99, 2392-2397
12. Rozengurt, N., Wu, S. V., Chen, M. C., Huang, C., Sternini, C., and Rozengurt, E. (2006) Colocalization of the a-subunit of gustducin with PYY and GLP-1 in L cells of human colon. Am. J. Physiol. Gastro-intest. Liver Physiol. 291, G792-G802
13. Finger, T. E., Böttger, B., Hansen, A., Anderson, K. T., Alimohammadi, H., and Silver, W. L. (2003) Solitary chemoreceptor cells in the nasal cavity serve as sentinels of respiration. Proc. Natl. Acad. Sci. USA 100, 8981-8986
14. Tizzano, M., Gulbransen, B. D., Vandenbeuch, A., Clapp, T. R., Herman, J. P., Sibhatu, H. M., Churchill, M. E. A., Silver, W. L., Kinnamon, S. C., and Finger, T. E. (2010) Nasal chemosensory cells use bitter taste signaling to detect irritants and bacterial signals. Proc. Natl. Acad. Sci. USA 107, 3210-3215
15. Deshpande, D. A., Wang, W. C., McIlmoyle, E. L., Robinett, K. S., Schillinger, R. M., An, S. S., Sham, J. S., and Liggett, S. B. (2010) Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction. Nat. Med. 16, 1299-1304
16. Foster, S. R., Porrello, E. R., Purdue, B., Chan, H. W., Voigt, A., Frenzel, S., Hannan, R. D., Moritz, K. M., Simmons, D. G., Molenaar, P., Roura, E., Boehm, U., Meyerhof, W., and Thomas, W. G. (2013) Expression, regulation and putative nutrient-sensing function of taste GPCRs in the heart. PLoS One 8, e64579
17. Orsmark-Pietras, C., James, A., Konradsen, J. R., Nordlund, B., Söderhäll, C., Pulkkinen, V., Pedroletti, C., Daham, K., Kupczyk, M., Dahlén, B., Kere, J., Dahlén, S. E., Hedlin, G., and Melén, E. (2013) Transcriptome analysis reveals upregulation of bitter taste receptors in severe asthmatics. Eur. Respir. J. 42, 65-78
18. Foster, S. R., Roura, E., and Thomas, W. G. (2014) Extrasensory perception: odorant and taste receptors beyond the nose and mouth. Pharmacol. Ther. 142, 41-61
19. Oliveira-Maia, A. J., Stapleton-Kotloski, J. R., Lyall, V., Phan, T. H., Mummalaneni, S., Melone, P., Desimone, J. A., Nicolelis, M. A., and Simon, S. A. (2009) Nicotine activates TRPM5-dependent and independent taste pathways. Proc. Natl. Acad. Sci. USA 106, 1596-1601
20. Upadhyaya, J. D., Singh, N., Sikarwar, A. S., Chakraborty, R., Pydi, S. P., Bhullar, R. P., Dakshinamurti, S., and Chelikani, P. (2014) Dextromethorphan mediated bitter taste receptor activation in the pulmonary circuit causes vasoconstriction. PLoS One 9, e110373
21. Liggett, S. B. (2014) Bitter taste receptors in the wrong place: novel airway smooth muscle targets for treating asthma. Trans. Am. Clin. Climatol. Assoc. 125, 64-75
22. Pawlowski, A. C., Johnson, J. W., and Wright, G. D. (2016) Evolving medicinal chemistry strategies in antibiotic discovery. Curr. Opin. Biotechnol. 42, 108-117
23. Miravitlles, M., and Anzueto, A. (2013) Antibiotics for acute and chronic respiratory infection in patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 188, 1052-1057
24. Sengupta, S., Chattopadhyay, M. K., and Grossart, H. P. (2013) The multifaceted roles of antibiotics and antibiotic resistance in nature. Front. Microbiol. 4, 47
25. Perry, J. A., and Wright, G. D. (2014) Forces shaping the antibiotic resistome. BioEssays 36, 1179-1184
26. Geller, D. E. (2009) Aerosolantibioticsincysticfibrosis. Respir. Care 54, 658-670
27. Culić, O., Eraković, V., and Parnham, M. J. (2001) Anti-inflammatory effects of macrolide antibiotics. Eur. J. Pharmacol. 429, 209-229
28. Good, J. T., Jr., Rollins, D. R., and Martin, R. J. (2012) Macrolides in the treatment of asthma. Curr. Opin. Pulm. Med. 18, 76-84
29. Rollins, D. R., Beuther, D. A., and Martin, R. J. (2010) Update on infection and antibiotics in asthma. Curr. Allergy Asthma Rep. 10, 67-73
30. Gao, X., Ray, R., Xiao, Y., Ishida, K., and Ray, P. (2010) Macrolide antibiotics improve chemotactic and phagocytic capacity as well as reduce inflammation in sulfur mustard-exposed monocytes. Pulm. Pharmacol. Ther. 23, 97-106
31. Suresh Babu, K., Kastelik, J., and Morjaria, J. B. (2013) Role of long term antibiotics in chronic respiratory diseases. Respir. Med. 107, 800-815
32. Badal, S., Her, Y. F., and Maher, L. J. (2015) Nonantibiotic effects of fluoroquinolones in mammalian cells. J. Biol. Chem. 290, 22287-22297
33. Hobson-Webb, L. D., Roach, E. S., and Donofrio, P. D. (2006) Metronidazole: newly recognized cause of autonomic neuropathy. J. Child Neurol. 21, 429-431
34. Park-Wyllie, L. Y., Juurlink, D. N., Kopp, A., Shah, B. R., Stukel, T. A., Stumpo, C., Dresser, L., Low, D. E., and Mamdani, M. M. (2006) Outpatient gatifloxacin therapy and dysglycemia in older adults. N. Engl. J. Med. 354, 1352-1361
35. Siva, R., Bafadhel, M., Monteiro, W., Brightling, C. E., and Pavord, I. D. (2014) Effect of levofloxacin on neutrophilic airway inflammation in stable COPD: a randomized, double-blind, placebo-controlled trial. Int. J. Chron. Obstruct. Pulmon. Dis. 9, 179-186
36. Kitazawa, T., Nakayama, K., Okugawa, S., Koike, K., Shibasaki, Y., and Ota, Y. (2007) Biphasic regulation of levofloxacin on lipopolysaccharide-induced IL-1b production. Life Sci. 80, 1572-1577
37. Huth, M. E., Han, K. H., Sotoudeh, K., Hsieh, Y. J., Effertz, T., Vu, A. A., Verhoeven, S., Hsieh, M. H., Greenhouse, R., Cheng, A. G., and Ricci, A. J. (2015) Designer aminoglycosides prevent cochlear hair cell loss and hearing loss. J. Clin. Invest. 125, 583-592
38. Jiang, M., Karasawa, T., and Steyger, P. S. (2017) Aminoglycoside-induced cochleotoxicity: a review. Front. Cell. Neurosci. 11, 308
39. Clark, A. A., Liggett, S. B., and Munger, S. D. (2012) Extraoral bitter taste receptors as mediators of off-target drug effects. FASEB J. 26, 4827-4831
40. Levit, A., Nowak, S., Peters, M., Wiener, A., Meyerhof, W., Behrens, M., and Niv, M. Y. (2014) The bitter pill: clinical drugs that activate the human bitter taste receptor TAS2R14. FASEB J. 28, 1181-1197
41. Dotson, C. D., Zhang, L., Xu, H., Shin, Y. K., Vigues, S., Ott, S. H., Elson, A. E., Choi, H. J., Shaw, H., Egan, J. M., Mitchell, B. D., Li, X., Steinle, N. I., and Munger, S. D. (2008) Bitter taste receptors influence glucose homeostasis. PLoS One 3, e3974
42. Meyerhof, W., Batram, C., Kuhn, C., Brockhoff, A., Chudoba, E., Bufe, B., Appendino, G., and Behrens, M. (2010) The molecular receptive ranges of human TAS2R bitter taste receptors. Chem. Senses 35, 157-170
43. Upadhyaya, J. D., Chakraborty, R., Shaik, F. A., Jaggupilli, A., Bhullar, R. P., and Chelikani, P. (2016) The pharmacochaperone activity of quinine on bitter taste receptors. PLoS One 11, e0156347
44. Chakraborty, R., Xu, B., Bhullar, R. P., and Chelikani, P. (2015) Expression of G protein-coupled receptors in mammalian cells. Methods Enzymol. 556, 267-281
45. Liu, K., Jaggupilli, A., Premnath, D., and Chelikani, P. (2018) Plasticity of the ligandbinding pocketinthe bittertaste receptorT2R7. Biochim. Biophys. Acta 1860, 991-999
46. Pydi, S. P., Jafurulla, M., Wai, L., Bhullar, R. P., Chelikani, P., and Chattopadhyay, A. (2016) Cholesterol modulates bitter taste receptor function. Biochim. Biophys. Acta 1858, 2081-2087
47. Upadhyaya, J., Singh, N., Bhullar, R. P., and Chelikani, P. (2015) The structure-function role of C-terminus in human bitter taste receptor T2R4 signaling. Biochim. Biophys. Acta 1848, 1502-1508
48. Jaggupilli, A., Singh, N., Jesus, V. C., Duan, K., and Chelikani, P. (2018) Characterization of the binding sites for bacterial acyl homoserine lactones (AHLs) on human bitter taste receptors (T2Rs). [E-pub ahead of print] ACS Infect. Dis. 10.1021/acsinfecdis.8b00094
49. Pydi, S. P., Sobotkiewicz, T., Billakanti, R., Bhullar, R. P., Loewen, M. C., and Chelikani, P. (2014) Amino acid derivatives as bitter taste receptor (T2R) blockers. J. Biol. Chem. 289, 25054-25066
50. Zhang, C., Alashi, A. M., Singh, N., Liu, K., Chelikani, P., and Aluko, R. E. (2018) Beef protein-derived peptides as bitter taste receptor T2R4 blockers. J. Agric. Food Chem. 66, 4902-4912
51. Singh, N., Pydi, S. P., Upadhyaya, J., and Chelikani, P. (2011) Structural basis of activation of bitter taste receptor T2R1 and comparison with Class A G-protein-coupled receptors (GPCRs). J. Biol. Chem. 286, 36032-36041
52. Uchida, T., Tanigake, A., Miyanaga, Y., Matsuyama, K., Kunitomo, M., Kobayashi, Y., Ikezaki, H., and Taniguchi, A. (2003) Evaluation of the bitterness of antibiotics using a taste sensor. J. Pharm. Pharmacol. 55, 1479-1485
53. Chmiel, J. F., Aksamit, T. R., Chotirmall, S. H., Dasenbrook, E. C., Elborn, J. S., LiPuma, J. J., Ranganathan, S. C., Waters, V. J., and Ratjen, F. A. (2014) Antibiotic management of lung infections in cystic fibrosis. II. Nontuberculous mycobacteria, anaerobic bacteria, and fungi. Ann. Am. Thorac. Soc. 11, 1298-1306
54. Stockmann, C., Sherwin, C. M., Zobell, J. T., Young, D. C., Waters, C. D., Spigarelli, M. G., and Ampofo, K. (2013) Optimization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: III. fluoroquinolones. Pediatr. Pulmonol. 48, 211-220
55. Roland, W. S., Gouka, R. J., Gruppen, H., Driesse, M., van Buren, L., Smit, G., and Vincken, J. P. (2014) 6-methoxyflavanonesas bitter taste receptor blockers for hTAS2R39. PLoS One 9, e94451
56. Yan, C. H., Hahn, S., McMahon, D., Bonislawski, D., Kennedy, D. W., Adappa, N. D., Palmer, J. N., Jiang, P., Lee, R. J., and Cohen, N. A. (2017) Nitric oxide production is stimulated by bitter taste receptors ubiquitously expressed in the sinonasal cavity. Am. J. Rhinol. Allergy 31, 85-92
57. Reichling, C., Meyerhof, W., and Behrens, M. (2008) Functions of human bitter taste receptors depend on N-glycosylation. J. Neurochem. 106, 1138-1148
58. Zhang, Y., Wang, X., Li, X., Peng, S., Wang, S., Huang, C. Z., Huang, C. Z., Zhang, Q., Li, D., Jiang, J., Ouyang, Q., Zhang, Y., Li, S., and Qiao, Y. (2017) Identification of a specific agonist of human TAS2R14 from Radix Bupleuri through virtual screening, functional evaluation and binding studies. Sci. Rep. 7, 12174
59. Sadarangani, S. P., Estes, L. L., and Steckelberg, J. M. (2015) Non-anti-infective effects of antimicrobials and their clinical applications: a review. Mayo Clin. Proc. 90, 109-127
60. Maurer, S., Wabnitz, G. H., Kahle, N. A., Stegmaier, S., Prior, B., Giese, T., Gaida, M. M., Samstag, Y., and Hänsch, G. M. (2015) Tasting Pseudomonasaeruginosabiofilms:human neutrophils express the bitter receptor T2R38 as sensor for the quorum sensing molecule N-(3-oxododecanoyl)-L-homoserine lactone. Front. Immunol. 6, 369
61. Gaida, M. M., Dapunt, U., and Hänsch, G. M. (2016) Sensing developing biofilms: the bitter receptor T2R38 on myeloid cells. Pathog. Dis. 74, ftw004
62. Sharma, P., Yi, R., Nayak, A. P., Wang, N., Tang, F., Knight, M. J., Pan, S., Oliver, B., and Deshpande, D. A. (2017) Bitter taste receptor agonists mitigate features ofallergic asthma in mice. Sci. Rep. 7, 46166