An antimicrobial peptide with trypanocidal activity characterized from Glossina morsitans morsitans.
Tsetse flies (Diptera:Glossinidae) are vectors of African trypanosomes, the protozoan agents of devastating diseases in humans and animals. Prior studies in trypanosome infected Glossina morsitans morsitans have shown induced expression and synthesis of several antimicrobial peptides in fat body tissue. Here, we have expressed one of these peptides, Attacin (GmAttA1) in Drosophila (S2) cells in vitro. We show that the purified recombinant protein (recGmAttA1) has strong antimicrobial activity against Escherichia coli-K12, but not against the enteric gram-negative symbiont of tsetse, Sodalis glossinidius. The recGmAttA1 also demonstrated inhibitory effects against both the mammalian bloodstream form and the insect stage Trypanosoma brucei in vitro (minimal inhibitory concentration MIC50 0.075 microM). When blood meals were supplemented with purified recGmAttA1 during the course of parasite infection, the prevalence of trypanosome infections in tsetse midgut was significantly reduced. Feeding fertile females GmAttA1 did not affect the fecundity or the longevity of mothers, nor did it affect the hatchability of their offspring. We discuss a paratransgenic strategy, which involves the expression of trypanocidal molecules such as recGmAttA1 in the midgut symbiont Sodalis in vivo to reduce trypanosome transmission.
Hu
Youjia
Y
Department of Epidemiology and Public Health, Section of Vector Biology, Yale University, School of Medicine, 60 College St., 606 LEPH, New Haven, CT 06510, USA.
Aksoy
Serap
S
D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D002460:Cell Line; D004331:Drosophila melanogaster; D004755:Enterobacteriaceae / Q000187:drug effects; D005260:Female; D019476:Insect Proteins / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D008969:Molecular Sequence Data; D010802:Phylogeny; D011994:Recombinant Proteins / Q000494:pharmacology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000494:pharmacology; D014370:Tsetse Flies / Q000737:chemistry* / Q000382:microbiology / Q000469:parasitology / Q000502:physiology
D000890:Anti-Infective Agents; D019476:Insect Proteins; D011994:Recombinant Proteins; D014344:Trypanocidal Agents; C039711:attacin antibacterial protein, insect