BT-R3 mediates killing of the malaria vector Anopheles gambiae by Bacillus thuringiensis

Aug 24, 2013

Researchers at The University of Texas at Dallas (UTD), led by Dr. Lee Bulla, have demonstrated for the first time the selective cytotoxicity of Bacillus thuringiensis subsp. israelensis Cry4B toxin is mediated by BT-R3. The Cry toxins produced by Bacillus thuringiensis exert their insecticidal activity by binding with high-affinity to their cognate cadherin receptors located on the surface of epithelial cells that line the midgut of susceptible insects. In the case of Anopheles gambiae, binding of the Cry4B toxin by BT-R3, in turn, triggers an internal signaling event that turns on a cell death pathway. The novelty of the research done by the UTD scientists is that they were able to establish the direct involvement of the BT-R3 receptor, cloned from Anopheles gambiae, in mediating toxicity of the Cry4B toxin in living cells. The research reported in this article in the July 2013 issue of Experimental Biology and Medicine is a culmination of proteomics, genomics and bioinformatics strategies developed in the Bulla laboratory.

Validation of BT-R3 as a functional receptor for Cry4B exemplifies the power of proteomics, genomics and bioinformatics to identify such as the BT-R3 receptor. The process of target selection starts with data mining of archived available in various genome and proteome databases, and results in the selection and annotation of candidate proteins based on their potential to mediate insecticidal action. It brings together genome- and -based target identification and target-directed screening for validating the action of insecticidal proteins such as the Cry4B toxin—engineered or otherwise. Targets selected for consideration can then be analyzed in silico by docking calculations, and other techniques to characterize appropriate target interactions with chemically or genetically altered Cry toxins.

Dr. Mohamed Ibrahim, senior author of the paper, said "this kind of strategy will facilitate protein design for creation of new customized Cry proteins and peptide mimics that might be more effective than the natural toxins themselves against Anopheles gambiae and other mosquitoes, and, hopefully, less able to bring about insect host resistance."

New approaches are needed in the area of malaria control because no effective vaccine currently exists and no available anti-malarial medications have been designed or discovered that impede parasite resistance with long-term use. A few drugs have been able to provide relief to patients but a preventive anti-malarial vaccine is yet to be developed. Certainly, genetic modification of wild mosquito vector populations to reduce vectorial capacity is fraught with unknown and hidden trials and tribulations.

Dr. Steve Goodman, Editor-in-Chief of Experimental Biology and Medicine said "Lee Bulla and his colleagues have combined genomics, proteomics and in silico analysis to establish the role of the cadherin receptor BT-R3 in the killing action of Cry4B mosquito toxin. Understanding of this Cry4B-BT-R3 complex will allow the design of custom proteins and peptides to help control the spread of malaria by mosquitoes".

Explore further: Scientists throw light on the mechanism of plants' ticking clock

add to favorites email to friend print save as pdf

Related Stories

Researchers identify insect resistance to Bt pesticide

Aug 30, 2011

For the first time, researchers have identified how cabbage looper caterpillars in the field develop resistance to the bacterium Bacillus thuringiensis (Bt), which naturally occurs in the soil and on plants ...

New bacteria toxins against resistant insect pests

Oct 19, 2011

Toxins from Bacillus thuringiensis bacteria (Bt toxins) are used in organic and conventional farming to manage pest insects. Sprayed as pesticides or produced in genetically modified plants, Bt toxins, us ...

Recommended for you

Fighting bacteria—with viruses

Jul 24, 2014

Research published today in PLOS Pathogens reveals how viruses called bacteriophages destroy the bacterium Clostridium difficile (C. diff), which is becoming a serious problem in hospitals and healthcare institutes, due to its re ...

Atomic structure of key muscle component revealed

Jul 24, 2014

Actin is the most abundant protein in the body, and when you look more closely at its fundamental role in life, it's easy to see why. It is the basis of most movement in the body, and all cells and components ...

Brand new technology detects probiotic organisms in food

Jul 23, 2014

In the food industr, ity is very important to ensure the quality and safety of products consumed by the population to improve their properties and reduce foodborne illness. Therefore, a team of Mexican researchers ...

Protein evolution follows a modular principle

Jul 23, 2014

Proteins impart shape and stability to cells, drive metabolic processes and transmit signals. To perform these manifold tasks, they fold into complex three-dimensional shapes. Scientists at the Max Planck ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

Doug_Huffman
not rated yet Aug 24, 2013
Oh noes! Here come the neo-Luddites eschewing another BT GMO for me to eat. Maybe this one will be a DDT adjuvant too.