CRISPR-Cas9 knockout of membrane-bound alkaline phosphatase or cadherin does not confer resistance to Cry toxins in Aedes aegypti

PLoS Negl Trop Dis. 2024 Jun 13;18(6):e0012256. doi: 10.1371/journal.pntd.0012256. eCollection 2024 Jun.

Abstract

The Aedes aegypti cadherin-like protein (Aae-Cad) and the membrane-bound alkaline phosphatase (Aae-mALP) are membrane proteins identified as putative receptors for the larvicidal Cry toxins produced by Bacillus thuringiensis subsp. israelensis bacteria. Cry toxins are the most used toxins in the control of different agricultural pest and mosquitos. Despite the relevance of Aae-Cad and Aae-mALP as possible toxin-receptors in mosquitoes, previous efforts to establish a clear functional connection among them and Cry toxins activity have been relatively limited. In this study, we used CRISPR-Cas9 to generate knockout (KO) mutations of Aae-Cad and Aae-mALP. The Aae-mALP KO was successfully generated, in contrast to the Aae-Cad KO which was obtained only in females. The female-linked genotype was due to the proximity of aae-cad gene to the sex-determining loci (M:m). Both A. aegypti KO mutant populations were viable and their insect-development was not affected, although a tendency on lower egg hatching rate was observed. Bioassays were performed to assess the effects of these KO mutations on the susceptibility of A. aegypti to Cry toxins, showing that the Aae-Cad female KO or Aae-mALP KO mutations did not significantly alter the susceptibility of A. aegypti larvae to the mosquitocidal Cry toxins, including Cry11Aa, Cry11Ba, Cry4Ba, and Cry4Aa. These findings suggest that besides the potential participation of Aae-Cad and Aae-mALP as Cry toxin receptors in A. aegypti, additional midgut membrane proteins are involved in the mode of action of these insecticidal toxins.

MeSH terms

  • Aedes* / genetics
  • Alkaline Phosphatase* / genetics
  • Alkaline Phosphatase* / metabolism
  • Animals
  • Bacillus thuringiensis / genetics
  • Bacillus thuringiensis / metabolism
  • Bacillus thuringiensis Toxins
  • Bacterial Proteins* / genetics
  • Bacterial Proteins* / metabolism
  • CRISPR-Cas Systems*
  • Cadherins* / genetics
  • Cadherins* / metabolism
  • Endotoxins* / genetics
  • Endotoxins* / metabolism
  • Female
  • Gene Knockout Techniques
  • Hemolysin Proteins / genetics
  • Hemolysin Proteins / metabolism
  • Insect Proteins / genetics
  • Insect Proteins / metabolism
  • Insecticide Resistance / genetics
  • Insecticides
  • Larva / genetics
  • Larva / growth & development
  • Male

Substances

  • Alkaline Phosphatase
  • Bacillus thuringiensis Toxins
  • Bacterial Proteins
  • Cadherins
  • Endotoxins
  • Hemolysin Proteins
  • Insect Proteins
  • insecticidal crystal protein, Bacillus Thuringiensis
  • Insecticides

Grants and funding

This work was supported by Dirección General de Asuntos del Personal Académico de la Universidad Nacional Autónoma de México - DGAPA/UNAM grant number: IN206721 (to SP) and DGAPA/UNAM grant number: IN210722 (to AB) and Consejo Nacional de Ciencia y Tecnología, Ciencia de Frontera grant number: CONACYT CF-6693 (to SP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.