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Chemosensory bitter taste receptors (T2Rs) are activated by multiple antibiotics
Author(s) -
Jaggupilli Appalaraju,
Singh Nisha,
De Jesus Vivianne Cruz,
Gounni Mohamed Soussi,
Dhanaraj Premnath,
Chelikani Prashen
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201800521rr
Subject(s) - antibiotics , receptor , tobramycin , biology , taste , microbiology and biotechnology , pharmacology , biochemistry , gentamicin
Many medications including antibiotics taste bitter. The potency of these antibiotics on the 25 bitter taste receptors (T2Rs) in humans remains poorly understood. Here we characterize by sensory and structure‐function analyses how antibiotics frequently used to treat airway infections in cystic fibrosis activate multiple human T2Rs. The potency of the broad‐spectrum antibiotics, tobramycin, levofloxacin, and azithromycin on the highly expressed T2Rs in airways, T2R4, T2R14, and T2R20 was pursued. The amino acids and structural features of T2R4, T2R14, and T2R20 important for antibiotic binding were characterized by mutational analysis in heterologous cell‐based assays. Strikingly, extracellular loop 2 in T2Rs performs a key function in binding to antibiotics with contribution from residues in transmembrane helices. Our results suggest that different antibiotics activate multiple T2Rs with different potencies. An understanding of the nonantibiotic and physiologic effects mediated through T2Rs on the host cells is much needed.—Jaggupilli, A., Singh, N., De Jesus, V. C., Gounni, M. S., Dhanaraj, P., Chelikani, P. Chemosensory bitter taste receptors (T2Rs) are activated by multiple antibiotics. FASEB J. 33, 501–517 (2019). www.fasebj.org