Individual Presentation or Panel Title
Dafachronic Acid Regulates Infectious Larvae Development in the Parasitic Nematode Strongyloides Stercoralis
Abstract
I will present about how dafachronic acid biosynthesis regulates the third-stage infectious larvae as well as the post-parasitic first-stage larvae in the parasitic nematode Strongyloides stercoralis. Strongyloides stercoralis is a parasitic nematode that infects 30 to 100 million people worldwide. The life-cycle of S. stercoralis is unique in that the infectious form of the parasite is a developmentally arrested third-stage larva (L3i). The larvae of the free-living nematode Caenorhabditis elegans go through a similar arrest stage called dauer under unfavorable conditions. In C. elegans, dauer entry and exit are controlled by dafachronic acid (DA) steroid ligands, which regulate the nuclear hormone receptor DAF-12. We hypothesized that endogenous production of DA is essential for L3i activation in S. stercoralis. To test this hypothesis, we used ketoconazole, a cytochrome P450 inhibitor, to inhibit the biosynthesis of DA and thus prevent the activation of the nuclear hormone receptor Ss-DAF-12. Ketoconazole inhibited L3i activation by biochemical host-like cues in S. stercoralis at 75 µM (17.1 ± 3.1% L3i feeding) compared to 80.6 ± 6.0% L3i feeding at 0 µM (p ≤ 0.01). We used exogenous ∆7-DA to rescue the L3i inhibited by ketoconazole; 400 nM ∆7- DA partially rescued the L3i larvae inhibited with 75 µM ketoconazole (50.1 ± 9.7% L3i feeding, p ≤ 0.01). Also, we have shown that Δ7-DA can regulate the developmental decision between the homogonic pathway in which the post-parasitic larvae (PPL1) develop directly into L3i and the heterogonic pathway in which the PPL1 molt four times and develop into adult males and females.
Location
Glass Dining Room
Start Date
11-4-2015 3:30 PM
End Date
11-4-2015 4:20 PM
Dafachronic Acid Regulates Infectious Larvae Development in the Parasitic Nematode Strongyloides Stercoralis
Glass Dining Room
I will present about how dafachronic acid biosynthesis regulates the third-stage infectious larvae as well as the post-parasitic first-stage larvae in the parasitic nematode Strongyloides stercoralis. Strongyloides stercoralis is a parasitic nematode that infects 30 to 100 million people worldwide. The life-cycle of S. stercoralis is unique in that the infectious form of the parasite is a developmentally arrested third-stage larva (L3i). The larvae of the free-living nematode Caenorhabditis elegans go through a similar arrest stage called dauer under unfavorable conditions. In C. elegans, dauer entry and exit are controlled by dafachronic acid (DA) steroid ligands, which regulate the nuclear hormone receptor DAF-12. We hypothesized that endogenous production of DA is essential for L3i activation in S. stercoralis. To test this hypothesis, we used ketoconazole, a cytochrome P450 inhibitor, to inhibit the biosynthesis of DA and thus prevent the activation of the nuclear hormone receptor Ss-DAF-12. Ketoconazole inhibited L3i activation by biochemical host-like cues in S. stercoralis at 75 µM (17.1 ± 3.1% L3i feeding) compared to 80.6 ± 6.0% L3i feeding at 0 µM (p ≤ 0.01). We used exogenous ∆7-DA to rescue the L3i inhibited by ketoconazole; 400 nM ∆7- DA partially rescued the L3i larvae inhibited with 75 µM ketoconazole (50.1 ± 9.7% L3i feeding, p ≤ 0.01). Also, we have shown that Δ7-DA can regulate the developmental decision between the homogonic pathway in which the post-parasitic larvae (PPL1) develop directly into L3i and the heterogonic pathway in which the PPL1 molt four times and develop into adult males and females.