Peptides 41 (2013) 87–93 Contents lists available at SciVerse ScienceDirect Peptides j ourna l ho me pa ge: www.elsevier.com/locate/peptides Review Cyt toxins produced by Bacillus thuringiensis: A protein fold conserved in several pathogenic microorganisms Mario Soberón, Jazmin A. López-Díaz, Alejandra Bravo ∗ Instituto de Biotecnología, Universidad Nacional Autónoma de México, Apdo. Postal 510-3, Cuernavaca 62250, Morelos, Mexico a r t i c l e i n f o Article history: Received 30 March 2012 Received in revised form 22 May 2012 Accepted 30 May 2012 Available online 9 June 2012 Keywords: Cyt toxin Bacillus thuringiensis Synergism a b s t r a c t Bacillus thuringiensis bacteria produce different insecticidal proteins known as Cry and Cyt toxins. Among them the Cyt toxins represent a special and interesting group of proteins. Cyt toxins are able to affect insect midgut cells but also are able to increase the insecticidal damage of certain Cry toxins. Furthermore, the Cyt toxins are able to overcome resistance to Cry toxins in mosquitoes. There is an increasing potential for the use of Cyt toxins in insect control. However, we still need to learn more about its mechanism of action in order to define it at the molecular level. In this review we summarize important aspects of Cyt toxins produced by Bacillus thuringiensis, including current knowledge of their mechanism of action against mosquitoes and also we will present a primary sequence and structural comparison with related proteins found in other pathogenic bacteria and fungus that may indicate that Cyt toxins have been selected by several pathogenic organisms to exert their virulence phenotypes. © 2012 Elsevier Inc. All rights reserved. Contents 1. Introduction ..... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 2. Structure and mechanism of action of Cyt toxins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 2.1. Interaction of Cyt toxin with the membrane and pore formation activity ..... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 3. Synergism between Cry and Cyt toxins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 3.1. Role of Cyt toxin in overcome resistance to Cry toxins in mosquitoes ..... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 4. Similarities of Cyt toxins with other proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 5. Final remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 1. Introduction Bacillus thuringiensis (Bt) bacteria produce different insecticidal toxins that have been used as an environmentally friendly alterna- tive method to control insect pests [4]. Bt produce crystal inclusions composed of Cry or Cyt toxins during sporulation phase of growth [4]. These proteins are ingested by the larvae and become soluble in the insect gut before inserting into the apical microvilli membrane of the insect-midgut cells. Cry and Cyt toxins belong to a class of bacterial toxins known as pore forming toxins (PFT) that in general are described as proteins that undergo conformational changes in Abbreviation: PFT, pore forming toxins. ∗ Corresponding author. Tel.: +52 777 3291635; fax: +52 777 3291624. E-mail addresses: mario@ibt.unam.mx (M. Soberón), jazald@ibt.unam.mx (J.A. López-Díaz), bravo@ibt.unam.mx (A. Bravo). order to insert into the membrane of their hosts, making pores that disrupt ion homeostasis and destroying the target cells [37]. Cry and Cyt toxins kill a limited number of insect species [3,4]. Cry toxins produced by different Bt strains show toxicity to differ- ent insect orders such as dipteran, coleopteran and lepidopteran, they have been used in the control of most important crop pests and mosquitoes. In contrast the Cyt toxins show mainly dipteran speci- ficity, being able to kill mosquitoes and black flies [13]. Mosquitoes are important vectors of human diseases such as malaria, yellow fever, dengue and lymphatic filariasis among others, causing mil- lions of deaths worldwide [14]. Although Cyt toxins are not toxic to the mayor lepidopteran pests [13,33], some Cyt toxins are able to kill coleopteran larvae, such as Cyt1Aa that is toxic to Chrysomela scripta [18] and Cyt2Ca that is toxic to Leptinotarsa decemlineata and Diabrotica spp [47]. 0196-9781/$ – see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.peptides.2012.05.023