A Shared Receptor Suggests a Common Ancestry between an Insecticidal Bacillus thuringiensis Cry Protein and an Anti-Cancer Parasporin

Biomolecules. 2024 Jul 4;14(7):795. doi: 10.3390/biom14070795.

Abstract

Cry toxins, produced by the bacterium Bacillus thuringiensis, are of significant agronomic value worldwide due to their potent and highly specific activity against various insect orders. However, some of these pore-forming toxins display specific activity against a range of human cancer cells whilst possessing no known insecticidal activity; Cry41Aa is one such toxin. Cry41Aa has similarities to its insecticidal counterparts in both its 3-domain toxic core structure and pore-forming abilities, but how it has evolved to target human cells is a mystery. This work shows that some insecticidal Cry toxins can enhance the toxicity of Cry41Aa against hepatocellular carcinoma cells, despite possessing no intrinsic toxicity themselves. This interesting crossover is not limited to human cancer cells, as Cry41Aa was found to inhibit some Aedes-active Cry toxins in mosquito larval assays. Here, we present findings that suggest that Cry41Aa shares a receptor with several insecticidal toxins, indicating a stronger evolutionary relationship than their divergent activities might suggest.

Keywords: Aedes aegypti; Cry1Ca; Cry41Aa; HepG2.

MeSH terms

  • Aedes / drug effects
  • Aedes / genetics
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Bacillus thuringiensis Toxins* / metabolism
  • Bacillus thuringiensis* / genetics
  • Bacillus thuringiensis* / metabolism
  • Bacterial Proteins* / chemistry
  • Bacterial Proteins* / genetics
  • Bacterial Proteins* / metabolism
  • Cell Line, Tumor
  • Endotoxins* / chemistry
  • Endotoxins* / genetics
  • Endotoxins* / metabolism
  • Hemolysin Proteins* / chemistry
  • Hemolysin Proteins* / genetics
  • Hemolysin Proteins* / metabolism
  • Hemolysin Proteins* / pharmacology
  • Humans
  • Insecticides / chemistry
  • Insecticides / pharmacology

Substances

  • Endotoxins
  • Bacterial Proteins
  • parasporin
  • Bacillus thuringiensis Toxins
  • Hemolysin Proteins
  • insecticidal crystal protein, Bacillus Thuringiensis
  • Insecticides
  • Antineoplastic Agents

Grants and funding

Michelle J. West is funded by grant 20003 from Blood Cancer UK.