Inhibition of Protein Synthesis in Intact HeLa Cells by Shigella Dysenteriae 1 Toxin

Overview

Journal Infect Immun

Publisher American Society for Microbiology

Specialty Allergy & Immunology

Date 1980 Jul 1

PMID 6156915

Citations 31

Authors

J E Brown

S W Rothman

B P Doctor

Affiliations

Soon will be listed here.

Abstract

Shiga toxin purified to near homogeneity from cell lysates of Shigella dysenteriae 1 inhibited protein and deoxyribonucle acid syntheses in intact HeLa cells. Inhibition was dependent on toxin concentration and time of incubation. A minimal latent period of 30 min was observed with saturating doses of toxin. Ribonucleic acid synthesis, uptake of alpha-aminoisobutyric acid, and maintenance of intracellular K+ concentrations were not affected until well after maximal inhibition of protein and deoxyribonucleic acid syntheses. The inhibitory effect of toxin was sensitive to heat inactivation and was prevented by antibody neutralization. Several cytotoxic components were separated by polyacrylamide gel electrophoresis of the purified toxin preparations; all inhibited protein and deoxyribonucleic acid syntheses equally.

Citing Articles

Synthesis of biologically active Shiga toxins in cell-free systems.

Ramm F, Kaser D, Konig I, Fellendorf J, Wenzel D, Zemella A Sci Rep. 2024; 14(1):6043.

PMID: 38472311 PMC: 11636806. DOI: 10.1038/s41598-024-56190-3.

Targeting the Inside of Cells with Biologicals: Toxin Routes in a Therapeutic Context.

Ruschig M, Marschall A BioDrugs. 2023; 37(2):181-203.

PMID: 36729328 PMC: 9893211. DOI: 10.1007/s40259-023-00580-y.

Molecular Biology of Shiga Toxins' Effects on Mammalian Cells.

Menge C Toxins (Basel). 2020; 12(5).

PMID: 32456125 PMC: 7290813. DOI: 10.3390/toxins12050345.

Targeting Eukaryotic mRNA Translation by .

Belyi Y Front Mol Biosci. 2020; 7:80.

PMID: 32411722 PMC: 7201127. DOI: 10.3389/fmolb.2020.00080.

A Legionella pneumophila Kinase Phosphorylates the Hsp70 Chaperone Family to Inhibit Eukaryotic Protein Synthesis.

Moss S, Taylor I, Ruggero D, Gestwicki J, Shokat K, Mukherjee S Cell Host Microbe. 2019; 25(3):454-462.e6.

PMID: 30827827 PMC: 6529236. DOI: 10.1016/j.chom.2019.01.006.

References

Lin J, Liu K, Chen C, TUNG T . Effect of crystalline ricin on the biosynthesis of protein, RNA, and DNA in experimental tumor cells. Cancer Res. 1971; 31(7):921-4. View

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

Grollman A . Inhibitors of protein biosynthesis. V. Effects of emetine on protein and nucleic acid biosynthesis in HeLa cells. J Biol Chem. 1968; 243(15):4089-94. View

Keusch G, GRADY G, Takeuchi A, SPRINZ H . The pathogenesis of shigella diarrhea. II. Enterotoxin-induced acute enteritis in the rabbit ileum. J Infect Dis. 1972; 126(1):92-5. DOI: 10.1093/infdis/126.1.92. View

Thompson M, Steinberg M, Gemski P, Formal S, Doctor B . Inhibition of in vitro protein synthesis by Shigella dysenteriae 1 toxin. Biochem Biophys Res Commun. 1976; 71(3):783-8. DOI: 10.1016/0006-291x(76)90899-8. View

VAN HEYNINGEN W, GLADSTONE G . The neurotoxin of Shigella shigae. I. Production, purification and properties of the toxin. Br J Exp Pathol. 1953; 34(2):202-16. PMC: 2073501. View

Davis B . DISC ELECTROPHORESIS. II. METHOD AND APPLICATION TO HUMAN SERUM PROTEINS. Ann N Y Acad Sci. 1964; 121:404-27. DOI: 10.1111/j.1749-6632.1964.tb14213.x. View

OLENICK J, Wolfe A . Shigella toxin inhibition of binding and translation of polyuridylic acid by Escherichia coli ribosomes. J Bacteriol. 1980; 141(3):1246-50. PMC: 293819. DOI: 10.1128/jb.141.3.1246-1250.1980. View

Binder H, Whiting D . Inhibition of small-intestinal sugar and amino acid transport by the enterotoxin of Shigella dysenteriae I. Infect Immun. 1977; 16(2):510-2. PMC: 420982. DOI: 10.1128/iai.16.2.510-512.1977. View

10.

Olsnes S, Eiklid K . Isolation and characterization of Shigella shigae cytotoxin. J Biol Chem. 1980; 255(1):284-9. View

11.

Keusch G, Jacewicz M . The pathogenesis of Shigella diarrhea. VI. Toxin and antitoxin in Shigella flexneri and Shigella sonnei infections in humans. J Infect Dis. 1977; 135(4):552-6. DOI: 10.1093/infdis/135.4.552. View

12.

Gorovsky M, Carlson K, Rosenbaum J . Simple method for quantitive densitometry of polyacrylamide gels using fast green. Anal Biochem. 1970; 35(2):359-70. DOI: 10.1016/0003-2697(70)90196-x. View

13.

Flores J, GRADY G, McIver J, Witkum P, Beckman B, SHARP G . Comparison of the effects of enterotoxins of Shigella dysenteriae and Vibrio cholerae on the adenylate cyclase system of the rabbit intestine. J Infect Dis. 1974; 130(4):374-9. DOI: 10.1093/infdis/130.4.374. View

14.

GEMSKI Jr P, Takeuchi A, WASHINGTON O, Formal S . Shigellosis due to Shigella dysenteriae. 1. Relative importance of mucosal invasion versus toxin production in pathogenesis. J Infect Dis. 1972; 126(5):523-30. DOI: 10.1093/infdis/126.5.523. View

15.

Keusch G, GRADY G, MATA L, McIver J . The pathogenesis of Shigella diarrhea. I. Enterotoxin production by Shigella dysenteriae I. J Clin Invest. 1972; 51(5):1212-8. PMC: 292252. DOI: 10.1172/JCI106915. View

16.

Olsnes S, Sandvig K, Eiklid K, Pihl A . Properties and action mechanism of the toxic lectin modeccin: interaction with cell lines resistant to modeccin, abrin, and ricin. J Supramol Struct. 1978; 9(1):15-25. DOI: 10.1002/jss.400090103. View

17.

Steinberg S, Banwell J, Yardley J, Keusch G, HENDRIX T . Comparison of secretory and histological effects of shigella and cholera enterotoxins in rabbit jejunum. Gastroenterology. 1975; 68(2):309-17. View

18.

Donowitz M, Keusch G, Binder H . Effect of Shigella enterotoxin on electrolyte transport in rabbit ileum. Gastroenterology. 1975; 69(6):1230-7. View

19.

VICARI G, Olitzki A, OLITZKI Z . The action of the thermolabile toxin of Shigella dysenteriae on cells cultivated in vitro. Br J Exp Pathol. 1960; 41:179-89. PMC: 2082365. View

20.

Labrec E, Schneider H, Magnani T, Formal S . EPITHELIAL CELL PENETRATION AS AN ESSENTIAL STEP IN THE PATHOGENESIS OF BACILLARY DYSENTERY. J Bacteriol. 1964; 88(5):1503-18. PMC: 277436. DOI: 10.1128/jb.88.5.1503-1518.1964. View