Cholix toxin, an eukaryotic elongation factor 2 ADP‐ribosyltransferase, interacts with Prohibitins and induces apoptosis with mitochondrial dysfunction in human hepatocytes

2019 ◽  
Vol 21 (8) ◽  
Author(s):  
Kinnosuke Yahiro ◽  
Kohei Ogura ◽  
Yasuhiro Terasaki ◽  
Mamoru Satoh ◽  
Satoru Miyagi ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Elongation Factor ◽  
Human Hepatocytes ◽  
Elongation Factor 2 ◽  
Eukaryotic Elongation Factor 2 ◽  
Eukaryotic Elongation Factor ◽  
Cholix Toxin ◽  
Adp Ribosyltransferase

scholarly journals Human α-defensins neutralize toxins of the mono-ADP-ribosyltransferase family

2006 ◽  
Vol 399 (2) ◽  
pp. 225-229 ◽  
Author(s):  
Chun Kim ◽  
Zoya Slavinskaya ◽  
A. Rod Merrill ◽  
Stefan H. E. Kaufmann
Keyword(s):  
Human Neutrophil ◽  
Biological Function ◽  
Elongation Factor ◽  
Bacterial Toxin ◽  
Pseudomonas Exotoxin ◽  
Pseudomonas Exotoxin A ◽  
Elongation Factor 2 ◽  
Eukaryotic Elongation Factor 2 ◽  
Eukaryotic Elongation Factor ◽  
Adp Ribosyltransferase

Various bacterial pathogens secrete toxins, which are not only responsible for fatal pathogenesis of disease, but also facilitate evasion of host defences. One of the best-known bacterial toxin groups is the mono-ADP-ribosyltransferase family. In the present study, we demonstrate that human neutrophil α-defensins are potent inhibitors of the bacterial enzymes, particularly against DT (diphtheria toxin) and ETA (Pseudomonas exotoxin A). HNP1 (human neutrophil protein 1) inhibited DT- or ETA-mediated ADP-ribosylation of eEF2 (eukaryotic elongation factor 2) and protected HeLa cells against DT- or ETA-induced cell death. Kinetic analysis revealed that inhibition of DT and ETA by HNP1 was competitive with respect to eEF2 and uncompetitive against NAD+ substrates. Our results reveal that toxin neutralization represents a novel biological function of HNPs in host defence.

scholarly journals Novel Cholix Toxin Variants, ADP-Ribosylating Toxins in Vibrio cholerae Non-O1/Non-O139 Strains, and Their Pathogenicity

2012 ◽  
Vol 81 (2) ◽  
pp. 531-541 ◽  
Author(s):  
Sharda Prasad Awasthi ◽  
Masahiro Asakura ◽  
Nityananda Chowdhury ◽  
Sucharit Basu Neogi ◽  
Atsushi Hinenoya ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Receptor Binding ◽  
Elongation Factor ◽  
Coagulation Necrosis ◽  
Ileal Loop ◽  
Content Type ◽  
Eukaryotic Elongation Factor 2 ◽  
Eukaryotic Elongation Factor ◽  
Cholix Toxin ◽  
Adp Ribosyltransferase

ABSTRACTCholix toxin (ChxA) is a recently discovered exotoxin inVibrio choleraewhich has been characterized as a third member of the eukaryotic elongation factor 2-specific ADP-ribosyltransferase toxins, in addition to exotoxin A ofPseudomonas aeruginosaand diphtheria toxin ofCorynebacterium diphtheriae. These toxins consist of three characteristic domains for receptor binding, translocation, and catalysis. However, there is little information about the prevalence ofchxAand its genetic variations and pathogenic mechanisms. In this study, we screened thechxAgene in a large number (n= 765) ofV. choleraestrains and observed its presence exclusively in non-O1/non-O139 strains (27.0%; 53 of 196) and not in O1 (n= 485) or O139 (n= 84). Sequencing of these 53chxAgenes generated 29 subtypes which were grouped into three clusters designatedchxAI,chxAII, andchxAIII.chxAI belongs to the prototype, whilechxAII andchxAIII are newly discovered variants. ChxA II and ChxA III had unique receptor binding and catalytic domains, respectively, in comparison to ChxA I. Recombinant ChxA I (rChxA I) and rChxA II but not rChxA III showed variable cytotoxic effects on different eukaryotic cells. Although rChxA II was more lethal to mice than rChxA I when injected intravenously, no enterotoxicity of any rChxA was observed in a rabbit ileal loop test. Hepatocytes showed coagulation necrosis in rChxA I- or rChxA II-treated mice, seemingly the major target for ChxA. The present study illustrates the potential of ChxA as an important virulence factor in non-O1/non-O139V. cholerae, which may be associated with extraintestinal infections rather than enterotoxicity.

scholarly journals Chaperone Function of Hgh1 in the Biogenesis of Eukaryotic Elongation Factor 2

2019 ◽  
Vol 74 (1) ◽  
pp. 88-100.e9 ◽  
Author(s):  
Leonie Mönkemeyer ◽  
Courtney L. Klaips ◽  
David Balchin ◽  
Roman Körner ◽  
F. Ulrich Hartl ◽  
...  
Keyword(s):  
Elongation Factor ◽  
Chaperone Function ◽  
Elongation Factor 2 ◽  
Eukaryotic Elongation Factor 2 ◽  
Eukaryotic Elongation Factor
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