Bacillus thuringiensis ( Bt ) crystal proteins are pore-forming toxins used as insecticides around the world. Previously, extent to which these might also target invertebrate phylum Nematoda has been mostly ignored. We have expressed seven different toxin from two largely unstudied protein subfamilies. By assaying their toxicity on diverse free-living nematode species, we demonstrate that four of active against multiple species and each tested is susceptible at least one toxin. a rat...

The development of pest resistance threatens the effectiveness Bacillus thuringiensis (Bt) toxins used in transgenic and organic farming. Here, we demonstrate that (i) major mechanism for Bt toxin Caenorhabditis elegans entails a loss glycolipid carbohydrates; (ii) directly specifically binds glycolipids; (iii) this binding is carbohydrate-dependent relevant action vivo. These carbohydrates contain arthroseries core conserved insects nematodes but lacking vertebrates. We present evidence...

Cytolytic pore-forming toxins are important for the virulence of many disease-causing bacteria. How target cells molecularly respond to these and whether or not they can mount a defense poorly understood. By using microarrays, we demonstrate that nematode Caenorhabditis elegans responds robustly Cry5B, member Crystal toxin family made by Bacillus thuringiensis . This genomic response is distinct from seen with different stressor, heavy metal cadmium. A p38 mitogen-activated protein kinase...

Abstract The protein toxins produced by Bacillus thuringiensis (Bt) are the most widely used natural insecticides in agriculture. Despite successful and extensive use of these transgenic crops, little is known about toxicity resistance pathways target insects since organisms not ideal for molecular genetic studies. To address this limitation to investigate potential control parasitic nematodes, we studying Bt toxin action Caenorhabditis elegans. We demonstrate first time that a single can...

The development of resistance is the main threat to long-term use toxins from Bacillus thuringiensis (Bt) in transgenic plants. Here we report cloning a Bt toxin gene, Caenorhabditis elegans bre-5, which encodes putative beta-1,3-galactosyltransferase. Lack bre-5 intestine led Cry5B. Wild-type but not mutant animals were found uptake into their gut cells, consistent with mutants lacking toxin-binding sites on apical gut. displayed Cry14A, lethal both nematodes and insects; this indicates...

Abstract During induction of the Caenorhabditis elegans hermaphrodite vulva by anchor cell gonad, six multipotent vulval precursor cells (VPCs) have two distinct fates: three VPCs generate and other nonspecialized hypodermis. Genes that control fates in response to signal are defined mutations cause all tissue (Multivulva or Muv) hypodermis (Vulvaless Vul). Seven dominant Vul were isolated as suppressors a lin-15 Muv mutation. These alleles gene let-60, previously identified only recessive...

Pore-forming toxins (PFTs) constitute the single largest class of proteinaceous bacterial virulence factors and are made by many most important pathogens. Host responses to these complex poorly understood. We find that endoplasmic reticulum unfolded protein response (UPR) is activated upon exposure PFTs both in Caenorhabditis elegans mammalian cells. Activation UPR protective vivo against since animals lack either ire-1-xbp-1 or atf-6 arms more sensitive PFT than wild-type animals. The acts...

Abstract The let-23 gene, which encodes a putative tyrosine kinase of the epidermal growth factor (EGF) receptor subfamily, has multiple functions during Caenorhabditis elegans development. We show that function is required for vulval precursor cells (VPCs) to respond signal induces differentiation: complete loss results in no induction. However, some mutations genetically reduce but do not eliminate result VPCs apparently hypersensitive inductive signal: as many five six can adopt fates,...

Here we present the first global functional analysis of cellular responses to pore-forming toxins (PFTs). PFTs are uniquely important bacterial virulence factors, comprising single largest class protein and being for pathogenesis in humans many Gram positive negative bacteria. Their mode action is deceptively simple, poking holes plasma membrane cells. The scattered studies date PFT-host cell interactions indicate a handful genes involved defenses PFTs. How against how coordinated unknown....

Soil-transmitted helminths are parasitic nematodes that inhabit the human intestine. These parasites, which include two hookworm species, Ancylostoma duodenale and Necator americanus, whipworm Trichuris trichiura, large roundworm Ascaris lumbricoides, infect upwards of billion people a major cause disease burden in children pregnant women. The challenge with treating these diseases is poverty, safety, inefficient public health policy have marginalized drug development distribution to control...

Erich Schwarz and colleagues report whole-genome sequencing of the zoonotic hookworm Ancylostoma ceylanicum. They also analyze transcriptome through course infection in golden hamsters identify groups genes showing differential regulation across different stages. Hookworms infect over 400 million people, stunting impoverishing them1,2,3. Sequencing genomes finding which they express during should help devising new drugs or vaccines against hookworms4,5. Unlike other hookworms, ceylanicum...

Chad A. Rappleye, Alexander R. Paredez, Carol W. Smith, Kent L. McDonald, and Raffi V. Aroian Department of Biology, The University California, San Diego, La Jolla, California 92093 USA; Electron Microscope Lab, Berkeley, 94720 USA

Crystal (Cry) proteins made by the bacterium Bacillus thuringiensis are pore-forming toxins that specifically target insects and nematodes used around world to kill insect pests. To better understand how interact with their host, we have screened for Caenorhabditis elegans mutants resist Cry protein intoxication. We find toxin resistance involves loss of two glycosyltransferase genes, bre-2 bre-4. These glycosyltransferases function in intestine confer susceptibility toxin. Furthermore, they...

Summary Our laboratory has demonstrated previously that Bacillus thuringiensis (Bt) crystal (Cry) proteins present in the Cry5 and Cry6 subclades intoxicate free‐living nematodes. In this study, we tested whether expression of nematicidal Cry6A transgenic plants provided protection against plant‐parasitic As bacterial codon usage is incompatible with plants, two different codon‐modified cry6A genes were synthesized for plants. One was designed by maintaining diversity whilst removing codons...

Pore-forming toxins (PFTs) are by far the most abundant bacterial protein and important for virulence of many pathogens. As such, cellular responses to PFTs critically modulate host-pathogen interactions. Although have been recorded, little is understood about their relevance pathological or defensive outcomes. To shed light on this question, we turned only genetic system studying PFT-host interactions—Caenorhabditis elegans intoxication Crystal (Cry) PFTs. We mutagenized screened C. mutants...

Intestinal parasitic nematodes such as hookworms, Ascaris lumbricoides, and Trichuris trichiura are amongst most prevalent tropical parasites in the world today. Although these cause a tremendous disease burden, we have very few anthelmintic drugs with which to treat them. In past three decades only one new anthelmintic, tribendimidine, has been developed taken into human clinical trials. Studies show that tribendimidine is safe good activity against hookworms. However, little known about...

Crystal (Cry) proteins are globally used in agriculture as proteinaceous insecticides. They have also been recently recognized to great potential anthelmintic agents targeting parasitic roundworms (e.g., hookworms). The most extensively characterized of the Cry is Cry5B. We report here 2.3 Å resolution structure proteolytically activated form This structure, which first for a nematicidal protein, shows familiar three-domain arrangement seen insecticidal proteins. However, domain II unusual...

Treatment of parasitic nematode infections in humans and livestock relies on a limited arsenal anthelmintic drugs that have historically reduced parasite burdens. However, resistance (AR) is increasing, little known about the molecular genetic causes for most drugs. The free-living roundworm Caenorhabditis elegans has proven to be tractable model understand AR, where studies led identification targets all major drug classes. Here, we used genetically diverse C . strains perform dose-response...

Crystal (Cry) proteins produced by the soil bacterium Bacillus thuringiensis (Bt) are harmless to vertebrates, but they highly toxic insects and nematodes. Their value in controlling that destroy crops transmit human diseases is well established. Although it has recently been demonstrated a few individual Bt Cry proteins, such as Cry5B, wide range of free-living nematodes, potential activity purified against parasitic nematodes remains largely unknown. We report here studies aimed at...