Antiplasmodial Activity Is an Ancient and Conserved Feature of Tick Defensins.
Ancestral sequence reconstruction has been widely used to test evolution-based hypotheses. The genome of the European tick vector,Ixodes ricinus, encodes for defensin peptides with diverse antimicrobial activities against distantly related pathogens. These pathogens include fungi, Gram-negative, and Gram-positive bacteria, i.e., a wide antimicrobial spectrum. Ticks do not transmit these pathogens, suggesting that these defensins may act against a wide range of microbes encountered by ticks during blood feeding or off-host periods. As demonstrated here, theseI. ricinusdefensins are also effective against the apicomplexan parasitePlasmodium falciparum. To study the general evolution of antimicrobial activity in tick defensins, the ancestral amino acid sequence of chelicerate defensins, which existed approximately 444 million years ago, was reconstructed using publicly available scorpion and tick defensin sequences (named Scorpions-Ticks Defensins Ancestor, STiDA). The activity of STiDA was tested againstP. falciparumand the same Gram-negative and Gram-positive bacteria that were used for theI. ricinusdefensins. While some extant tick defensins exhibit a wide antimicrobial spectrum, the ancestral defensin showed moderate activity against one of the tested microbes,P. falciparum. This study suggests that amino acid variability and defensin family expansion increased the antimicrobial spectrum of ancestral tick defensins.
Institute of Parasitology, Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - Centre d'Infection et d'Immunité de LilleLille, France; Institute of Parasitology, Biology Centre of the Czech Academy of Sciences (ACVR)České Budějovice, Czech Republic; Faculty of Science, University of South BohemiaČeské Budějovice, Czech Republic.
Alejandro
A
Cabezas-Cruz
Department of Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology Giessen, Germany.
Miray
M
Tonk
Institute of Parasitology, Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - Centre d'Infection et d'Immunité de Lille Lille, France.
Anne
A
Bouchut
Institute of Parasitology, Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - Centre d'Infection et d'Immunité de Lille Lille, France.
Christine
C
Pierrot
Institute of Parasitology, Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - Centre d'Infection et d'Immunité de Lille Lille, France.
Raymond J
RJ
Pierce
Institute of Parasitology, Biology Centre of the Czech Academy of Sciences (ACVR) České Budějovice, Czech Republic.
Michalis
M
Kotsyfakis
Department of Bioresources, Fraunhofer Institute for Molecular Biology and Applied EcologyGiessen, Germany; Institute for Insect Biotechnology, Justus-Liebig-University of GiessenGiessen, Germany.
Mohammad
M
Rahnamaeian
Department of Bioresources, Fraunhofer Institute for Molecular Biology and Applied EcologyGiessen, Germany; Institute for Insect Biotechnology, Justus-Liebig-University of GiessenGiessen, Germany.
Andreas
A
Vilcinskas
Institute of Parasitology, Université Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - Centre d'Infection et d'Immunité de Lille Lille, France.
Jamal
J
Khalife
Institute of Parasitology, Biology Centre of the Czech Academy of Sciences (ACVR)České Budějovice, Czech Republic; Department of Virology, Veterinary Research InstituteBrno, Czech Republic.
James J
JJ
Valdés
Plasmodium falciparum; ancestral sequence reconstruction; antimicrobial spectrum; defensins; ticks