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

Appalaraju Jaggupilli1, Nisha Singh1, Vivianne Cruz De Jesus1

  • 1Manitoba Chemosensory Biology Research Group and Department of Oral Biology, University of Manitoba, Children's Hospital Research Institute of Manitoba (CHRIM), Winnipeg, Manitoba, Canada.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|July 17, 2018
PubMed

Insights

Multiple antibiotics activate bitter taste receptors (T2Rs), impacting airway infections. Understanding these interactions is crucial for potential therapeutic applications and patient experience.

Area of Science:

  • Pharmacology
  • Chemosensation
  • Molecular Biology

Background:

  • Many medications, including antibiotics, elicit a bitter taste, influencing patient adherence.
  • The specific interactions between antibiotics and human bitter taste receptors (T2Rs) are not well-defined.

Purpose of the Study:

  • To characterize how common antibiotics activate human T2Rs, focusing on those expressed in airways.
  • To elucidate the structural basis of antibiotic binding to T2Rs.

Main Methods:

  • Sensory and structure-function analyses were employed.
  • Mutational analysis in cell-based assays identified key amino acids and structural features for antibiotic binding.
  • Potency of tobramycin, levofloxacin, and azithromycin on T2R4, T2R14, and T2R20 was assessed.

Main Results:

  • Antibiotics activate multiple human T2Rs with varying potencies.
  • Extracellular loop 2 of T2Rs, along with residues in transmembrane helices, is critical for antibiotic binding.
  • Specific T2Rs highly expressed in airways (T2R4, T2R14, T2R20) are activated by these antibiotics.

Conclusions:

  • Antibiotics can activate multiple bitter taste receptors (T2Rs).
  • The structural mechanisms of antibiotic-T2R interactions, particularly involving extracellular loop 2, have been elucidated.
  • Further research is needed to understand the physiological consequences of T2R activation by non-bitter compounds.
Keywords:
GPCRcystic fibrosislevofloxacinstructure-functiontobramycin

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