title: Bacillus sphaericus binary toxin elicits host cell autophagy as a response to intoxication.
abstract: 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.
authors.affiliation: Institut National de la Recherche Agronomique, UMR Interactions Biotiques et Santé Végétale, INRA 1301-CNRS 6243-Université de Nice Sophia Antipolis, Sophia Antipolis, France. onya.opota@epfl.ch
authors.forename: Onya
authors.initials: O
authors.lastname: Opota
authors.forename: Nils C
authors.initials: NC
authors.lastname: Gauthier
authors.forename: Anne
authors.initials: A
authors.lastname: Doye
authors.forename: Colin
authors.initials: C
authors.lastname: Berry
authors.forename: Pierre
authors.initials: P
authors.lastname: Gounon
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Lemichez
authors.forename: David
authors.initials: D
authors.lastname: Pauron
mesh_terms: D000818:Animals; D000852:Anopheles / Q000201:enzymology / Q000235:genetics; D001343:Autophagy / Q000187:drug effects*; D016863:Bacillaceae Infections / Q000378:metabolism / Q000473:pathology*; D001407:Bacillus / Q000378:metabolism; D001427:Bacterial Toxins / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D002478:Cells, Cultured; D003465:Culex / Q000201:enzymology / Q000235:genetics; D004285:Dogs; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000502:physiology; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000520:alpha-Glucosidases / Q000235:genetics / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D011993:Recombinant Fusion Proteins; C046134:binB protein, Bacillus sphaericus; D049452:Green Fluorescent Proteins; D000520:alpha-Glucosidases