Bacillus sphaericus binary toxin elicits host cell autophagy as a response to intoxication

PLoS One. 2011 Feb 14;6(2):e14682. doi: 10.1371/journal.pone.0014682.


Bacillus sphaericus strains that produce the binary toxin (Bin) are highly toxic to Culex and Anopheles mosquitoes, and have been used since the late 1980s as a biopesticide for the control of these vectors of infectious disease agents. The Bin toxin produced by these strains targets mosquito larval midgut epithelial cells where it binds to Cpm1 (Culex pipiens maltase 1) a digestive enzyme, and causes severe intracellular damage, including a dramatic cytoplasmic vacuolation. The intoxication of mammalian epithelial MDCK cells engineered to express Cpm1 mimics the cytopathologies observed in mosquito enterocytes following Bin ingestion: pore formation and vacuolation. In this study we demonstrate that Bin-induced vacuolisation is a transient phenomenon that affects autolysosomes. In addition, we show that this vacuolisation is associated with induction of autophagy in intoxicated cells. Furthermore, we report that after internalization, Bin reaches the recycling endosomes but is not localized either within the vacuolating autolysosomes or within any other degradative compartment. Our observations reveal that Bin elicits autophagy as the cell's response to intoxication while protecting itself from degradation through trafficking towards the recycling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anopheles / enzymology
  • Anopheles / genetics
  • Autophagy / drug effects*
  • Bacillaceae Infections / metabolism
  • Bacillaceae Infections / pathology*
  • Bacillus / metabolism
  • Bacterial Toxins / metabolism
  • Bacterial Toxins / pharmacology
  • Bacterial Toxins / toxicity*
  • Cells, Cultured
  • Culex / enzymology
  • Culex / genetics
  • Dogs
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Host-Pathogen Interactions / drug effects
  • Host-Pathogen Interactions / physiology
  • Phagosomes / drug effects
  • Phagosomes / metabolism
  • Phagosomes / pathology
  • Recombinant Fusion Proteins / metabolism
  • Transfection
  • Vacuoles / drug effects
  • Vacuoles / metabolism
  • Vacuoles / pathology
  • alpha-Glucosidases / genetics
  • alpha-Glucosidases / metabolism


  • Bacterial Toxins
  • Recombinant Fusion Proteins
  • binB protein, Bacillus sphaericus
  • Green Fluorescent Proteins
  • alpha-Glucosidases