PMID- 31335899
OWN - NLM
STAT- MEDLINE
DCOM- 20200102
LR  - 20200309
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 15
IP  - 7
DP  - 2019 Jul
TI  - Dafachronic acid promotes larval development in Haemonchus contortus by 
      modulating dauer signalling and lipid metabolism.
PG  - e1007960
LID - 10.1371/journal.ppat.1007960 [doi]
LID - e1007960
AB  - 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.
FAU - Ma, Guangxu
AU  - Ma G
AUID- ORCID: 0000-0002-5929-7887
AD  - Department of Veterinary Biosciences, Melbourne Veterinary School, The University 
      of Melbourne, Parkville, Victoria, Australia.
FAU - Wang, Tao
AU  - Wang T
AUID- ORCID: 0000-0003-1359-8913
AD  - Department of Veterinary Biosciences, Melbourne Veterinary School, The University 
      of Melbourne, Parkville, Victoria, Australia.
FAU - Korhonen, Pasi K
AU  - Korhonen PK
AUID- ORCID: 0000-0002-9957-4674
AD  - Department of Veterinary Biosciences, Melbourne Veterinary School, The University 
      of Melbourne, Parkville, Victoria, Australia.
FAU - Young, Neil D
AU  - Young ND
AD  - Department of Veterinary Biosciences, Melbourne Veterinary School, The University 
      of Melbourne, Parkville, Victoria, Australia.
FAU - Nie, Shuai
AU  - Nie S
AD  - Bio21 Mass Spectrometry and Proteomics Facility, The University of Melbourne, 
      Parkville, Victoria, Australia.
FAU - Ang, Ching-Seng
AU  - Ang CS
AD  - Bio21 Mass Spectrometry and Proteomics Facility, The University of Melbourne, 
      Parkville, Victoria, Australia.
FAU - Williamson, Nicholas A
AU  - Williamson NA
AUID- ORCID: 0000-0002-2173-3452
AD  - Bio21 Mass Spectrometry and Proteomics Facility, The University of Melbourne, 
      Parkville, Victoria, Australia.
FAU - Reid, Gavin E
AU  - Reid GE
AD  - School of Chemistry, The University of Melbourne, Parkville, Victoria, Australia.
AD  - Department of Biochemistry and Molecular Biology, The University of Melbourne, 
      Parkville, Victoria, Australia.
AD  - Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, 
      Parkville, Victoria, Australia.
FAU - Gasser, Robin B
AU  - Gasser RB
AD  - Department of Veterinary Biosciences, Melbourne Veterinary School, The University 
      of Melbourne, Parkville, Victoria, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190723
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 
      (4-(1-((5-((2,6-dimethylphenoxy)methyl)-3-isoxazolyl)carbonyl)-4-piperidinyl)pyridine)
RN  - 0 (Cholestenes)
RN  - 0 (Helminth Proteins)
RN  - 0 (Isoxazoles)
RN  - 0 (Piperidines)
RN  - 0 (Pyridines)
RN  - 0 (delta7-dafachronic acid)
SB  - IM
MH  - Animals
MH  - Cholestenes/*metabolism
MH  - Gene Expression Regulation, Developmental
MH  - Genes, Helminth
MH  - Haemonchiasis/parasitology/veterinary
MH  - Haemonchus/*growth & development/*metabolism/pathogenicity
MH  - Helminth Proteins/chemistry/genetics/metabolism
MH  - Isoxazoles/pharmacology
MH  - Larva/drug effects/growth & development/metabolism
MH  - Lipid Metabolism/drug effects
MH  - Piperidines/pharmacology
MH  - Pyridines/pharmacology
MH  - Sheep
MH  - Sheep Diseases/parasitology
MH  - Sheep, Domestic
MH  - Signal Transduction
PMC - PMC6677322
COIS- The authors have declared that no competing interests exist.
EDAT- 2019/07/25 06:00
MHDA- 2020/01/03 06:00
PMCR- 2019/07/23
CRDT- 2019/07/24 06:00
PHST- 2019/04/17 00:00 [received]
PHST- 2019/07/04 00:00 [accepted]
PHST- 2019/08/02 00:00 [revised]
PHST- 2019/07/25 06:00 [pubmed]
PHST- 2020/01/03 06:00 [medline]
PHST- 2019/07/24 06:00 [entrez]
PHST- 2019/07/23 00:00 [pmc-release]
AID - PPATHOGENS-D-19-00703 [pii]
AID - 10.1371/journal.ppat.1007960 [doi]
PST - epublish
SO  - PLoS Pathog. 2019 Jul 23;15(7):e1007960. doi: 10.1371/journal.ppat.1007960. 
      eCollection 2019 Jul.