Ketoconazole inhibits developmental activation of <i>Strongyloides stercoralis</i> iL3 in host-like culture conditions; this inhibition is rescued by Δ7-dafachronic acid. Mennatallah M. Y. Albarqi Jonathan D. Stoltzfus Adeiye A. Pilgrim Thomas J. Nolan Zhu Wang Steven A. Kliewer David J. Mangelsdorf James B. Lok 10.1371/journal.ppat.1005358.g005 https://plos.figshare.com/articles/figure/_Ketoconazole_inhibits_developmental_activation_of_Strongyloides_stercoralis_iL3_in_host_like_culture_conditions_this_inhibition_is_rescued_by_7_dafachronic_acid_/1632489 <p>Frequency of feeding by cultured larvae, as reflected by ingestion of fluorescein isothiocyanate (FITC), was used as an index of developmental activation of infectious third-stage larvae (iL3). Larval mortality was scored as the percentage of larvae classed as non-motile and therefore “dead.” (A) Frequency of iL3 feeding and larval mortality as a function of ketoconazole concentration in Dulbecco’s modified Eagle’s Medium (DMEM), a permissive culture medium. DMEM without ketoconazole was the positive control. M9 buffer, a non-permissive medium, was used without ketoconazole as the negative control. ** Negative correlation of iL3 feeding and ketoconazole concentration (bracketed) is significant (P = 0.0028; Spearman r = -1.000). (B) Frequency of iL3 feeding and larval mortality as a function of Δ7-dafachronic acid (Δ7-DA) concentration in DMEM cultures containing an inhibitory concentration of ketoconazole (35 μM). Cultures of larvae in DMEM alone or in DMEM with 800 nM Δ7-DA were positive controls. Cultures of larvae in M9 buffer constituted the negative control. * Positive correlation of iL3 feeding in 35 μM ketoconazole and Δ7-DA concentration (bracketed) is significant (P = 0.0167; Spearman r = 1.000). In both panels, bar heights represent the mean percentage of iL3 feeding (blue bars) or the mean percentage of dead iL3 (white bars) in four biological replicates. Error bars indicate +1 standard deviation.</p> 2016-01-05 14:56:13 CYP inhibitor ketoconazole 1 μ M Δ7- DA post-parasitic first-stage larvae post-parasitic L 1s iL 3 activation 400 nM Δ7- DA nematode Strongyloides stercoralis hormone receptor DAF -12. Biosynthesis DAF -9. 35 μ M ketoconazole 26 CYP-encoding genes free-living nematode Caenorhabditis elegans DAF -12 iL 3 arrest DA production SD Δ7- DA exposure 40 μ M ketoconazole stercoralis development iL 3 cytochrome P 450 post-free-living iL 3 arrest Life Cycle Checkpoints