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Antimicrobial Agents and Chemotherapy, July 2002, p. 2104-2110, Vol. 46, No. 7
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.7.2104-2110.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Design and Activity of Antimicrobial Peptides against Sporogonic-Stage Parasites Causing Murine Malarias

Romanico B. G. Arrighi,1,2,3,{dagger} Chikashi Nakamura,2 Jun Miyake,2 Hilary Hurd,3* and J. Grant Burgess1

Center for Applied Entomology and Parasitology, School of Life Sciences, Keele University, Keele, Staffordshire ST5 5BG,3 Department of Biological Sciences, Heriot-Watt University, Riccarton, Edinburgh EH14 4AS, United Kingdom,1 Tissue Biosensor Team, Tissue Engineering Research Center, The National Institute of Advanced Industrial Science and Technology, 1-1-1 Higashi, Tsukuba, 305-8562 Japan2

Received 7 December 2001/ Returned for modification 8 March 2002/ Accepted 4 April 2002

Insects produce several types of peptides to combat a broad spectrum of invasive pathogenic microbes, including protozoans. However, despite this defense response, infections are often established. Our aim was to design novel peptides that produce high rates of mortality among protozoa of the genus Plasmodium, the malaria parasites. Using existing antimicrobial peptide sequences as templates, we designed and synthesized three short novel hybrids, designated Vida1 to Vida3. Each has a slightly different predicted secondary structure. The peptides were tested against sporogonic stages of the rodent malaria parasites Plasmodium berghei (in vitro and in vivo) and P. yoelii nigeriensis (in vitro). The level of activity varied for each peptide and according to the parasite stage targeted. Vida3 (which is predicted to have large numbers of ß sheets and coils but no {alpha} helices) showed the highest level of activity, killing the early sporogonic stages in culture and causing highly significant reductions in the prevalence and intensity of infection of P. berghei after oral administration or injection in Anopheles gambiae mosquitoes. The secondary structures of these peptides may play a crucial role in their ability to interact with and kill sporogonic forms of the malaria parasite.

* Corresponding author. Mailing address: Centre for Applied Entomology and Parasitology, School of Life Sciences, Keele University, Keele, Staffordshire, ST5 5BG, United Kingdom. Phone: (44) 1782583034. Fax: (44) 1782583516. E-mail: h.hurd{at}biol.keele.ac.uk.

{dagger} Present address: Centre for Applied Entomology and Parasitology, School of Life Sciences, Keele University, Keele, Staffordshire, ST5 5BG, United Kingdom.

Antimicrobial Agents and Chemotherapy, July 2002, p. 2104-2110, Vol. 46, No. 7
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.7.2104-2110.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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