Plant cyclotides disrupt epithelial cells in the midgut of lepidopteran larvae

doi:10.1073/pnas.0710338104

Plant cyclotides disrupt epithelial cells in the midgut of lepidopteran larvae

Departments of *Biochemistry and
^†Zoology, and
^‡Analytical Electron Microscopy Laboratory, La Trobe University, Melbourne, Victoria 3086, Australia; and
^§Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia

Communicated by Adrienne Clarke, University of Melbourne, Victoria, Australia, October 30, 2007 (received for review February 1, 2007)

Abstract

Several members of the Rubiaceae and Violaceae plant families produce a series of cyclotides or macrocyclic peptides of 28–37 aa with an embedded cystine knot. The cyclic peptide backbone together with the knotted and strongly braced structure confers exceptional chemical and biological stability that has attracted attention for potential pharmaceutical applications. Cyclotides display a diverse range of biological activities, such as uterotonic action, anti-HIV activity, and neurotensin antagonism. In plants, their primary role is probably protection from insect attack. Ingestion of the cyclotide kalata B1 severely retards the growth of larvae from the Lepidopteran species Helicoverpa armigera. We examined the gut of these larvae after consumption of kalata B1 by light, scanning, and transmission electron microscopy. We established that kalata B1 induces disruption of the microvilli, blebbing, swelling, and ultimately rupture of the cells of the gut epithelium. The histology of this response is similar to the response of H. armigera larvae to the Bacillus thuringiensis delta-endotoxin, which is widely used to control these insect pests of crops such as cotton.

Footnotes

^¶To whom correspondence should be addressed. E-mail: m.anderson{at}latrobe.edu.au
Author contributions: B.L.B. and M.A.A. designed research; B.L.B. and A.T.M. performed research; D.J.C. contributed new reagents/analytic tools; B.L.B., A.T.M., A.D.G., and M.A.A. analyzed data; and B.L.B., A.D.G., and M.A.A. wrote the paper.
The authors declare no conflict of interest.