Safety assessment of Mpp75Aa1.1, a new ETX_MTX2 protein from Brevibacillus laterosporus that controls western corn rootworm

PLoS One. 2022 Sep 8;17(9):e0274204. doi: 10.1371/journal.pone.0274204. eCollection 2022.

Abstract

The recently discovered insecticidal protein Mpp75Aa1.1 from Brevibacillus laterosporus is a member of the ETX_MTX family of beta-pore forming proteins (β-PFPs) expressed in genetically modified (GM) maize to control western corn rootworm (WCR; Diabrotica virgifera virgifera LeConte). In this manuscript, bioinformatic analysis establishes that although Mpp75Aa1.1 shares varying degrees of similarity to members of the ETX_MTX2 protein family, it is unlikely to have any allergenic, toxic, or otherwise adverse biological effects. The safety of Mpp75Aa1.1 is further supported by a weight of evidence approach including evaluation of the history of safe use (HOSU) of ETX_MTX2 proteins and Breviballus laterosporus. Comparisons between purified Mpp75Aa1.1 protein and a poly-histidine-tagged (His-tagged) variant of the Mpp75Aa1.1 protein demonstrate that both forms of the protein are heat labile at temperatures at or above 55°C, degraded by gastrointestinal proteases within 0.5 min, and have no adverse effects in acute mouse oral toxicity studies at a dose level of 1920 or 2120 mg/kg body weight. These results support the use of His-tagged proteins as suitable surrogates for assessing the safety of their non-tagged parent proteins. Taken together, we report that Mpp75Aa1.1 is the first ETX-MTX2 insecticidal protein from B. laterosporus and displays a similar safety profile as typical Cry proteins from Bacillus thuringiensis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacillus thuringiensis* / genetics
  • Bacillus thuringiensis* / metabolism
  • Bacterial Proteins / metabolism
  • Brevibacillus
  • Coleoptera* / genetics
  • Endotoxins / metabolism
  • Insecticides* / pharmacology
  • Larva / metabolism
  • Mice
  • Pest Control, Biological / methods
  • Plants, Genetically Modified / genetics
  • Plants, Genetically Modified / metabolism
  • Zea mays / genetics
  • Zea mays / metabolism

Substances

  • Bacterial Proteins
  • Endotoxins
  • Insecticides

Supplementary concepts

  • Brevibacillus laterosporus

Grants and funding

The study was supported by Bayer Crop Science and no outside funding for any author was received. The authors received no specific funding for this work.