Promise of
            <i>Bacillus thuringiensis</i>
            Crystal Proteins as Anthelmintics

Hu, Yan; Aroian, Raffi V.

doi:10.1002/9783527652969.ch16

Cited by 6 publications

(10 citation statements)

References 82 publications

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“…In C. elegans the p38 mitogen activated protein kinase (MAPK) pathway protects against Cry5B (Kao et al, 2011). A similar situation has been found in hookworms, for example, A. ceylanicum (Hu et al, 2012a), demonstrating that C. elegans is likely to be a good model for the study of these toxins in nematodes.…”

Section: Crystal (Cry) Proteins From Bacillus Thuringiensis: Cry5b Cmentioning

confidence: 79%

“…These mutants also show defects in the production of polar glycolipids which act as receptors for Cry5B (Griffiths et al, 2005). These carbohydrates contain the arthroseries core which is present in nematodes but absent in vertebrates (Hu and Aroian, 2012b). Cry protein monomers bind to intestinal cell receptors, oligomerize, and enter the plasma membrane to form pores.…”

Section: Crystal (Cry) Proteins From Bacillus Thuringiensis: Cry5b Cmentioning

confidence: 99%

“…Cry proteins are pore-forming proteins made by the Gram-positive bacterium, Bacillus thuringiensis (Hu and Aroian, 2012a;Hu and Aroian, 2012b). Though first used as insecticides, these compounds have since been shown to have anthelmintic properties, including against C. elegans (Kotze et al, 2005;Wei et al, 2003).…”

Section: Crystal (Cry) Proteins From Bacillus Thuringiensis: Cry5b Cmentioning

confidence: 99%

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Anthelmintic drugs and nematicides: studies in Caenorhabditis elegans

Holden‐Dye

Walker²

2014

WormBook

130

129

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Section: Crystal (Cry) Proteins From Bacillus Thuringiensis: Cry5b Cmentioning

confidence: 79%

Section: Crystal (Cry) Proteins From Bacillus Thuringiensis: Cry5b Cmentioning

confidence: 99%

Section: Crystal (Cry) Proteins From Bacillus Thuringiensis: Cry5b Cmentioning

confidence: 99%

See 1 more Smart Citation

Anthelmintic drugs and nematicides: studies in Caenorhabditis elegans

Holden‐Dye

Walker²

2014

WormBook

130

129

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“…7 Cry5B is a member of the three-domain B. thuringiensis Cry proteins, which are pore-forming proteins that target the invertebrate (insect/nematode) intestine, in the case of Cry5B by binding to invertebrate-specific glycolipids present on the apical surface of the nematode intestine. 8 …”

mentioning

confidence: 99%

Protection and Delivery of Anthelmintic Protein Cry5B to Nematodes Using Mesoporous Silicon Particles

Miller

et al. 2015

ACS Nano

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The ability of nano- and microparticles of partially oxidized mesoporous silicon (pSi) to sequester, protect, and deliver the anthelmintic pore-forming protein Cry5B to nematodes is assessed in vitro and in vivo. Thermally oxidized pSi particles are stable under gastric conditions and show relatively low toxicity to nematodes. Fluorescence images of rhodamine-labeled pSi particles within the nematodes Caenorhabditis elegans and Ancylostoma ceylanicum show that ingestion is dependent on particle size: particles of a 0.4 ± 0.2 μm size are noticeably ingested by both species within 2 h of introduction in vitro, whereas 5 ±2 μm particles are excluded from C. elegans but enter the pharynx region of A. ceylanicum after 24 h. The anthelmintic protein Cry5B, a pore-forming crystal (Cry) protein derived from Bacillus thuringiensis, is incorporated into the pSi particles by aqueous infiltration. Feeding of Cry5B-loaded pSi particles to C. elegans leads to significant intoxication of the nematode. Protein-loaded particles of size 0.4 μm display the highest level of in vitro toxicity toward C. elegans on a drug-mass basis. The porous nanostructure protects Cry5B from hydrolytic and enzymatic (pepsin) degradation in simulated gastric fluid (pH 1.2) for time periods up to 2 h. In vivo experiments with hookworm-infected hamsters show no significant reduction in worm burden with the Cry5B-loaded particles, which is attributed to slow release of the protein from the particles and/or short residence time of the particles in the duodenum of the animal.

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“…This assembling is also true of Cry5B produced in B. thuringiensis (40). Whereas no crystals were detected upon sporulation of the PY79-vector strain (Fig.…”

Section: Resultsmentioning

confidence: 84%

Bacillus subtilis Strain Engineered for Treatment of Soil-Transmitted Helminth Diseases

Miller

Derman

et al. 2013

Appl Environ Microbiol

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c Soil-transmitted helminths (hookworms, whipworms, and large roundworms) are agents of intestinal roundworm diseases of poverty that infect upwards of 2 billion people worldwide. A great challenge in treating these diseases is the development of anthelmintic therapeutics that are inexpensive, can be produced in great quantity, and are capable of delivery under varied and adverse environmental conditions. A potential solution to this challenge is the use of live bacteria that are acceptable for human consumption, e.g., Bacillus subtilis, and that can be engineered with therapeutic properties. In this study, we expressed the Bacillus thuringiensis anthelmintic protein Cry5B in a bacterial strain that has been used as a model for live bacterial therapy, Bacillus subtilis PY79. PY79 transformed with a Cry5B expression plasmid (PY79-Cry5B) is able to express Cry5B from the endogenous B. thuringiensis cry5B promoter. During sporulation of PY79-Cry5B, Cry5B is packaged as a crystal. Furthermore, Cry5B produced in PY79 is bioactive, with a 50% lethal concentration (LC 50 ) of 4.3 g/ml against the roundworm Caenorhabditis elegans. PY79-Cry5B was a significantly effective therapeutic in experimental Ancylostoma ceylanicum hookworm infections of hamsters. A single 10-mg/kg (0.071 mol/kg of body weight) dose of Cry5B administered as a Cry5B-PY79 spore crystal lysate achieved a 93% reduction in hookworm burdens, which is superior on a molar level to reductions seen with clinically used anthelmintics. Given that a bacterial strain such as this one can be produced cheaply in massive quantities, our results demonstrate that the engineering and delivery of live bacterial strains have great potential to treat a significant contributor to poverty worldwide, namely, hookworm disease and other soil-transmitted helminthiasis.

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Promise of Bacillus thuringiensis Crystal Proteins as Anthelmintics

Cited by 6 publications

References 82 publications

Anthelmintic drugs and nematicides: studies in Caenorhabditis elegans

Anthelmintic drugs and nematicides: studies in Caenorhabditis elegans

Protection and Delivery of Anthelmintic Protein Cry5B to Nematodes Using Mesoporous Silicon Particles

Bacillus subtilis Strain Engineered for Treatment of Soil-Transmitted Helminth Diseases

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