Journal article

Dafachronic acid promotes larval development in Haemonchus contortus by modulating dauer signalling and lipid metabolism

Guangxu Ma, Tao Wang, Pasi K Korhonen, Neil D Young, Shuai Nie, Ching-Seng Ang, Nicholas A Williamson, Gavin E Reid, Robin B Gasser

PLOS PATHOGENS | PUBLIC LIBRARY SCIENCE | Published : 2019

Abstract

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 metaboli..

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Grants

Funding Acknowledgements

Funding from the Australian Research Council (ARC), the National Health and Medical Research Council (NHMRC) of Australia and Melbourne Water Corporation and The University of Melbourne (BIP) is gratefully acknowledged (all authors). PKK holds an NHMRC Early Career Research Fellowship, and NDY holds an NHMRC Career Development Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.