Gambicin: A novel immune responsive antimicrobial peptide from the malariavector Anopheles gambiae

A novel mosquito antimicrobial peptide, gambicin, and the corresponding gen e were isolated in parallel through differential display-PCR, an expressed sequence tag (EST) project, and characterization of an antimicrobial activi ty in a mosquito cell line by reverse-phase chromatography. The 616-bp gamb icin ORF encodes an 81-residue protein that is processed and secreted as a 61-aa mature peptide containing eight cysteines engaged in four disulfide b ridges. Gambicin lacks sequence homology with other known proteins. Like ot her Anopheles gambiae antimicrobial peptide genes, gambicin is induced by n atural or experimental infection in the midgut, fatbody, and hemocyte-like cell lines. Within the midgut, gambicin is predominantly expressed in the a nterior part. Both local and systemic gambicin expression is induced during early and late stages of natural malaria infection. In vitro experiments s howed that the 6.8-kDa mature peptide can kill both Gram-positive and Gram- negative bacteria, has a morphogenic effect on a filamentous fungus, and is marginally lethal to Plasmodium berghei ookinetes. An oxidized form of gam bicin isolated from the cell line medium was more active against bacteria t han the nonoxidized form from the same medium.