Effect of geldanamycin on hatching and motility in Caenorhabditis elegans and Heterodera glycines.

Authors: Skantar, Andrea; AGAMA, KELI; MEYER, SUSAN; CARTA, LYNN; Vinyard, Bryan

Submitted to: Journal of Chemical Ecology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/22/2004
Publication Date: 10/1/2005
Citation: Skantar, A.M., Agama, K.K., Meyer, S.L., Carta, L.K., Vinyard, B.T. 2005. Effect of geldanamycin on hatching and motility in Caenhorhabditis elegans and Heterodera glycines. Journal of Chemical Ecology 31:2481-2491.

Interpretive Summary: Soybean cyst nematode (SCN) is the most economically important pest of soybean worldwide, causing annual yield losses of $600 million. One problem with controlling these crop losses is that there are no natural, environmentally safe ways to disrupt egg hatch or movement of the early life stages that are vulnerable in the soil. Understanding the proteins that govern how nematodes control their development in response to stress can also lead to the discovery of safe ways of nematode management. We used a naturally occurring antibiotic called geldanamycin to study the function of one such protein believed to govern nematode responses to stresses such as increased temperature. We have discovered that geldanamycin can reduce egg hatching and movement in SCN and a related non-parasitic nematode. These results are significant because they represent the first demonstration of geldanamycin effects in any species of nematode, thereby making this compound a valuable new tool for studying nematode stress responses. In addition, the results indicate that the bacterium that naturally produces geldanamycin should be evaluated for its ability to control nematodes. These findings will be used by scientists developing control strategies for many types of nematodes.

Technical Abstract: Here we show that the Hsp90 heat-shock chaperone inhibitor geldanamycin interferes with egg hatch and juvenile motility in both the free-living Caenorhabditis elegans and the plant-parasite Heterodera glycines. Five doses of geldanamycin ranging from 2 to 100 ug/ml were tested in microtiter wells on both heat shocked and non-heat shocked C. elegans eggs, and eggs from three populations of H. glycines. Proportions of eggs that hatched and proportions of hatched motile nematodes were measured after 20 hours for C. elegans or four days for H. glycines. Significant effects occurred at low doses, and some surprising reversals occurred at higher doses. Caenorhabditis elegans had U-shaped hatch and motility curves, where heat shock exaggerated hatch rate reduction but moderated the decline in motility. Basal hatch rates of H. glycines population NL1-RH varied significantly. In one trial where the control hatch rate was 35%, both hatching and motility curves were U-shaped as in C. elegans. In a second trial of the same population, with half the control hatch rate of the first trial, there is a U-shaped hatch curve, but an inverse U-shape for motility. For fast-hatching population TN17 and slow-hatching TN18, where control hatch rates are low (12-16%), both hatch and motility curves have inverse U shapes. Multimodal U-shaped and inverse U-shaped dose-response curves are discussed in relation to high proportions of readily hatching versus inducible-hatching subpopulations. While eldanamycin has been previously shown to suppress plant pathogenic fungi, these results are the first such demonstration of GA effects in any species of free-living, animal-parasitic or plant-parasitic nematode. Hsp90 is discussed as an important but complex component of nematode stress response and developmental arrest pathways.