Histone deacetylase enzymes as drug targets for the control of the sheep blowfly, Lucilia cuprina

Kotze, Andrew C., Hines, Barney M., Bagnall, Neil H., Anstead, Clare A., Gupta, Praveer, Reid, Robert C., Ruffell, Angela P. and Fairlie, David P. (2015) Histone deacetylase enzymes as drug targets for the control of the sheep blowfly, Lucilia cuprina. International Journal for Parasitology: Drugs and Drug Resistance, 5 3: 201-208. doi:10.1016/j.ijpddr.2015.09.003

Author Kotze, Andrew C.
Hines, Barney M.
Bagnall, Neil H.
Anstead, Clare A.
Gupta, Praveer
Reid, Robert C.
Ruffell, Angela P.
Fairlie, David P.
Title Histone deacetylase enzymes as drug targets for the control of the sheep blowfly, Lucilia cuprina
Journal name International Journal for Parasitology: Drugs and Drug Resistance   Check publisher's open access policy
ISSN 2211-3207
Publication date 2015-12-01
Sub-type Article (original research)
DOI 10.1016/j.ijpddr.2015.09.003
Open Access Status DOI
Volume 5
Issue 3
Start page 201
End page 208
Total pages 8
Place of publication Oxford, United Kingdom
Publisher Elsevier
Collection year 2016
Language eng
Formatted abstract
The Australian sheep blowfly, Lucilia cuprina, is an ecto-parasite that causes significant economic losses in the sheep industry. Emerging resistance to insecticides used to protect sheep from this parasite is driving the search for new drugs that act via different mechanisms. Inhibitors of histone deacetylases (HDACs), enzymes essential for regulating eukaryotic gene transcription, are prospective new insecticides based on their capacity to kill human parasites. The blowfly genome was found here to contain five HDAC genes corresponding to human HDACs 1, 3, 4, 6 and 11. The catalytic domains of blowfly HDACs 1 and 3 have high sequence identity with corresponding human and other Dipteran insect HDACs (Musca domestica and Drosophila melanogaster). On the other hand, HDACs 4, 6 and 11 from the blowfly and the other Dipteran species showed up to 53 % difference in catalytic domain amino acids from corresponding human sequences, suggesting the possibility of developing HDAC inhibitors specific for insects as desired for a commercial insecticide. Differences in transcription patterns for different blowfly HDACs through the life cycle, and between the sexes of adult flies, suggest different functions in regulating gene transcription within this organism and possibly different vulnerabilities. Data that supports HDACs as possible new insecticide targets is the finding that trichostatin A and suberoylanilide hydroxamic acid retarded growth of early instar blowfly larvae in vitro, and reduced the pupation rate. Trichostatin A was 8-fold less potent than the commercial insecticide cyromazine in inhibiting larval growth. Our results support further development of inhibitors of blowfly HDACs with selectivity over human and other mammalian HDACs as a new class of prospective insecticides for sheep blowfly.
Keyword Histone deacetylase
Lucilia cuprina
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
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