title: Induction of autophagy by anthrax lethal toxin.
abstract: Autophagy is an evolutionary conserved intracellular process whereby cells break down long-lived proteins and organelles. Accumulating evidences suggest increasing physiological significance of autophagy in pathogenesis of infectious diseases. Anthrax lethal toxin (LT) exerts its influence on numerous cells and herein, we report a novel effect of LT-induced autophagy on mammalian cells. Several autophagy biochemical markers including LC3-II conversion, increased punctuate distribution of GFP-LC3 and development of acidic vesicular organelles (AVO) were detected in cells treated with LT. Analysis of individual LT component revealed a moderate increase in LC3-II conversion for protective antigen-treated cells, whereas the LC3-II level in lethal factor-treated cells remained unchanged. In addition, our preliminary findings suggest a protective role of autophagy in LT intoxication as autophagy inhibition resulted in accelerated cell death. This study presents a hitherto undescribed effect of LT-induced autophagy on cells and provides the groundwork for future studies on the implication of autophagy in anthrax pathogenesis.
authors.affiliation: Molecular and Microbiology Department, College of Sciences, George Mason University, Manassas, VA 22010, USA.
authors.forename: Yian Kim
authors.initials: YK
authors.lastname: Tan
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Kusuma
authors.forename: Lena J
authors.initials: LJ
authors.lastname: St John
authors.forename: Hao A
authors.initials: HA
authors.lastname: Vu
authors.forename: Kenneth
authors.initials: K
authors.lastname: Alibek
authors.forename: Aiguo
authors.initials: A
authors.lastname: Wu
mesh_terms: D000165:Acridine Orange / Q000737:chemistry; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000942:Antigens, Bacterial / Q000633:toxicity*; D001343:Autophagy / Q000187:drug effects; D001427:Bacterial Toxins / Q000633:toxicity*; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D014617:Vacuoles / Q000737:chemistry / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; C030325:anthrax toxin; D049452:Green Fluorescent Proteins; C025946:3-methyladenine; D000165:Acridine Orange; D000225:Adenine