title: Plasmodium yoelii: correlation of TEP1 with mosquito melanization induced by nitroquine.
abstract: The antimalarial drug nitroquine is not only an effective antimalarial drug, it is also able to induce the melanization of Plasmodium species. However, the molecular mechanisms of the recognition reaction induced by this drug remain unclear. Silencing of thioester-containing protein-1 (TEP1) significantly compromised the ability of Anopheles gambiae to melanize the Plasmodium, leading to investigation of the involvement of A. stephensi TEP1 in melanization induced by nitroquine. This study shows that (1) binding of AsTEP1 to oocysts, especially melanized oocysts, (2) after ingestion of anti-AsTEP1 antibody, the melanization rate in antibody-treated mosquitoes are significantly lower than in control mosquito (p<0.05). The results suggest that nitroquine is able to induce Plasmodium recognition by TEP1, possibly triggering the resulting melanotic encapsulation. Further elucidation of the molecular mechanisms of mosquito immunity induced by antimalarial drugs will provide theoretical evidence for the use of antimalarial drugs, and a meaningful pathway for the design of novel antimalarial drugs.
authors.affiliation: Department of the Pathogenic Biology, The Third Military Medical University, Chongqing 400038, PR China. zhangjiansp@163.com
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Fu Sheng
authors.initials: FS
authors.lastname: Huang
authors.forename: Wen Yue
authors.initials: WY
authors.lastname: Xu
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Tao Li
authors.initials: TL
authors.lastname: Zhou
authors.forename: Jian Hua
authors.initials: JH
authors.lastname: Duan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000235:genetics / Q000378:metabolism / Q000469:parasitology*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005260:Female; D019476:Insect Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D007303:Insect Vectors / Q000235:genetics / Q000378:metabolism / Q000469:parasitology*; D008543:Melanins / Q000378:metabolism*; D051379:Mice; D023421:Models, Animal; D033661:Oocysts / Q000378:metabolism; D010967:Plasmodium yoelii / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011799:Quinazolines / Q000494:pharmacology*; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018076:DNA, Complementary; D019476:Insect Proteins; D008543:Melanins; D011799:Quinazolines; C544265:TEP1 protein, Anopheles gambiae; C021126:nitroquine