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

Lookup NU author(s): Professor Grant Burgess

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Abstract

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 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


Publication metadata

Author(s): Burgess JG; Arrigi RBG; Nakamura C; Miyake J; Hurd H

Publication type: Article

Publication status: Published

Journal: Antimicrobial Agents and Chemotherapy

Year: 2002

Volume: 46

Issue: 7

Pages: 2104-2110

ISSN (print): 0066-4804

ISSN (electronic): 1098-6596

Publisher: American Society for Microbiology

URL: http://dx.doi.org/10.1128/AAC.46.7.2104-2110.2002

DOI: 10.1128/AAC.46.7.2104-2110.2002

PubMed id: 12069961


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