title: Modulation of Anopheles stephensi gene expression by nitroquine, an antimalarial drug against Plasmodium yoelii infection in the mosquito.
abstract: BACKGROUND
  Antimalarial drugs may impact mosquito's defense against Plasmodium parasites. Our previous study showed nitroquine significantly reduced infection of Anopheles stephensi by Plasmodium yoelii, but the underlying mechanism remains unclear. In order to understand how transmission capacity of An. stephensi was affected by nitroquine, we explored the transcriptome of adult females after different treatments, examined changes in gene expression profiles, and identified transcripts affected by the drug and parasite.
  
  
  RESULTS
  We extended massively parallel sequencing and data analysis (including gene discovery, expression profiling, and function prediction) to An. stephensi before and after Plasmodium infection with or without nitroquine treatment. Using numbers of reads assembled into specific contigs to calculate relative abundances (RAs), we categorized the assembled contigs into four groups according to the differences in RA values infection induced, infection suppressed, drug induced, and drug suppressed. We found both nitroquine in the blood meal and Plasmodium infection altered transcription of mosquito genes implicated in diverse processes, including pathogen recognition, signal transduction, prophenoloxidase activation, cytoskeleton assembling, cell adhesion, and oxidative stress. The differential gene expression may have promoted certain defense responses of An. stephensi against the parasite and decreased its infectivity.
  
  
  CONCLUSIONS
  Our study indicated that nitroquine may regulate several immune mechanisms at the level of gene transcription in the mosquito against Plasmodium infection. This highlights the need for better understanding of antimalarial drug's impact on parasite survival and transmission. In addition, our data largely enriched the existing sequence information of An. stephensi, an epidemiologically important vector species.
authors.affiliation: Department of Pathobiology, The Third Military Medical University, Chongqing, P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Entomology and Plant Pathology, Oklahoma State University, Stillwater, Oklahoma, United States of America.
authors.forename: Shuguang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pathobiology, The Third Military Medical University, Chongqing, P. R. China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathobiology, The Third Military Medical University, Chongqing, P. R. China.
authors.forename: Wenyue
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Pathobiology, The Third Military Medical University, Chongqing, P. R. China.
authors.forename: Jingru
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Entomology and Plant Pathology, Oklahoma State University, Stillwater, Oklahoma, United States of America.
authors.forename: Haobo
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Pathobiology, The Third Military Medical University, Chongqing, P. R. China.
authors.forename: Fusheng
authors.initials: F
authors.lastname: Huang
mesh_terms: D000818:Animals; D000852:Anopheles / Q000235:genetics* / Q000469:parasitology; D000962:Antimalarials / Q000494:pharmacology*; D009033:Culicidae / Q000235:genetics* / Q000469:parasitology; D005260:Female; D007303:Insect Vectors / Q000187:drug effects / Q000235:genetics; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D010967:Plasmodium yoelii / Q000187:drug effects*; D011799:Quinazolines / Q000494:pharmacology*; D059467:Transcriptome / Q000187:drug effects* / Q000235:genetics
chemical_list: D000962:Antimalarials; D011799:Quinazolines; C021126:nitroquine