Figure 1.

P. aeruginosa quinolones activate multiple T2Rs. a, chemical structures of quinine ((R)-[(2S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methanol), chloroquine (4-N-(7-chloroquinolin-4-yl)-1-N,1-N-diethylpentane-1,4-diamine), PQS (2-heptyl-3-hydroxy-4(1H)-quinolone), HHQ (4-hydroxy-2-heptylquinolone), and DHQ (2,4-dihydroxyquinolone). b, peak [Ca²⁺]_i responses of T2Rs to 100 μm PQS in HEK293Ts transfected with Gα₁₆/gust44 alone or Gα₁₆/gust44 plus human (h) TAS2R4, TAS2R5, TAS2R14, TAS2R16, TAS2R38 (PAV isoform), TAS2R39, TAS2R40, TAS2R41, or TAS2R46. c, representative trace of PQS response in Gα₁₆/gust44 only-transfected cells as well as cells transfected with Gα₁₆/gust44 plus hTAS2R5 or hTAS2R46 (which did not respond to PQS) or hTAS2R4, hTAS2R16, hTAS2R38, or hTAS2R39 (which responded to PQS). Results in b and c were obtained by measuring the entire cell population (entire field of view, containing both transfected and nontransfected cells); peak responses when specific responding cells were selected are shown in Fig. S1 for comparison. Responses were larger when only responding cells were selected, but taking the entire population measurement removes potential biasing. d, peak [Ca²⁺]_i responses (from the entire population as in b) with 100 μm DHQ and 100 μm HHQ in HEK293Ts transfected with Gα₁₆/gust44 alone or Gα₁₆/gust44 plus hTAS2R4, TAS2R14, TAS2R16, or TAS2R38. e, representative trace of HHQ response in hTAS2R14 + Gα₁₆/gust44–transfected and Gα₁₆/gust44 only–transfected cells. Bar graphs in b and d show mean ± S.E. (error bars) of 4–10 independent experiments/condition. Significance was determined by one-way ANOVA with Dunnett's post-test using Gα₁₆/gust44 only–transfected cells as control: *, p < 0.05; **, p < 0.01.