Dafachronic acid promotes larval development in Haemonchus contortus by modulating dauer signalling and lipid metabolism
AuthorMa, G; Wang, T; Korhonen, PK; Young, ND; Nie, S; Ang, C-S; Williamson, NA; Reid, GE; Gasser, RB
Source TitlePLOS PATHOGENS
PublisherPUBLIC LIBRARY SCIENCE
University of Melbourne Author/sAng, Ching-Seng; Ma, Guangxu; Wang, Tao; Korhonen, Pasi; Young, Neil; Nie, Shuai; Williamson, Nicholas; Reid, Gavin; Gasser, Robin
School of Chemistry
Melbourne Veterinary School
Document TypeJournal Article
CitationsMa, G., Wang, T., Korhonen, P. K., Young, N. D., Nie, S., Ang, C. -S., Williamson, N. A., Reid, G. E. & Gasser, R. B. (2019). Dafachronic acid promotes larval development in Haemonchus contortus by modulating dauer signalling and lipid metabolism. PLOS PATHOGENS, 15 (7), https://doi.org/10.1371/journal.ppat.1007960.
Access StatusOpen Access
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC6677322
Here, we discovered an endogenous dafachronic acid (DA) in the socioeconomically important parasitic nematode Haemonchus contortus. We demonstrate that DA promotes larval exsheathment and development in this nematode via a relatively conserved nuclear hormone receptor (DAF-12). This stimulatory effect is dose- and time-dependent, and relates to a modulation of dauer-like signalling, and glycerolipid and glycerophospholipid metabolism, likely via a negative feedback loop. Specific chemical inhibition of DAF-9 (cytochrome P450) was shown to significantly reduce the amount of endogenous DA in H. contortus; compromise both larval exsheathment and development in vitro; and modulate lipid metabolism. Taken together, this evidence shows that DA plays a key functional role in the developmental transition from the free-living to the parasitic stage of H. contortus by modulating the dauer-like signalling pathway and lipid metabolism. Understanding the intricacies of the DA-DAF-12 system and associated networks in H. contortus and related parasitic nematodes could pave the way to new, nematode-specific treatments.
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