Brief exposures of human body lice to sublethal amounts of ivermectin over-transcribes detoxification genes involved in tolerance.

TitleBrief exposures of human body lice to sublethal amounts of ivermectin over-transcribes detoxification genes involved in tolerance.
Publication TypeJournal Article
Year of Publication2011
AuthorsYoon, KS, Strycharz, JP, Baek, JH, Sun, W, Kim, JH, Kang, JS, Pittendrigh, BR, Lee, SH, Clark, JM
JournalInsect Mol Biol
Volume20
Issue6
Pagination687-99
Date Published2011 Dec
ISSN1365-2583
KeywordsAnimals, Antiparasitic Agents, ATP-Binding Cassette Transporters, Cytochrome P-450 Enzyme System, Dexamethasone, Drug Resistance, Female, Gene Expression Profiling, Gene Expression Regulation, Genes, Insect, Humans, Inactivation, Metabolic, Ivermectin, Pediculus, Phylogeny, RNA Interference, Verapamil
Abstract

Transcriptional profiling results, using our non-invasive induction assay {short exposure intervals (2-5 h) to sublethal amounts of insecticides [< lethal concentration 3% (LC(3)) at 24 h] administered by stress-reducing means (contact vs. immersion screen) and with induction assessed in a time frame when tolerance is still present [~lethal concentration 90% (LC(90)) in 2-4 h]}, showed that ivermectin-induced detoxification genes from body lice are identified by quantitative real-time PCR analyses. Of the cytochrome P450 monooxygenase and ATP binding cassette transporter genes induced by ivermectin, CYP6CJ1, CYP9AG1, CYP9AG2 and PhABCC4 were respectively most significantly over-expressed, had high basal expression levels and were most closely related to genes from other organisms that metabolized insecticides, including ivermectin. Injection of double-stranded RNAs (dsRNAs) against either CYP9AG2 or PhABCC4 into non-induced female lice reduced their respective transcript level and resulted in increased sensitivity to ivermectin, indicating that these two genes are involved in the xenobiotic metabolism of ivermectin and in the production of tolerance.

DOI10.1111/j.1365-2583.2011.01097.x
Alternate JournalInsect Mol Biol
PubMed ID21895817
PubMed Central IDPMC3208734
Grant ListR01 AI045062 / AI / NIAID NIH HHS / United States
R01 AI045062-06 / AI / NIAID NIH HHS / United States
R56 AI081933-01A2 / AI / NIAID NIH HHS / United States
5R01 AI045062-06 / AI / NIAID NIH HHS / United States