Modeling neutralization of Shiga 2 toxin by A-and B-subunit-specific human monoclonal antibodies
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A mathematical model for Shiga 2 toxin neutralization by A-and B-subunit-specific human monoclonal antibodies initially delivered in the extracellular domain is presented, taking into account toxin and antibodies interaction in the extracellular domain, diffusion of toxin, antibodies, and their reaction products toward the cell, the receptor-mediated toxin and complex composed of toxin and antibody to A-subunit internalization from the extracellular into the intracellular medium and excretion of this complex back to the extracellular environment via recycling endosomal carriers. The retrograde transport of the intact toxin to the endoplasmic reticulum and its anterograde movement back to the vicinity of the plasma membrane with its subsequent exocytotic removal to the extracellular space via the secretory vesicle pathway is also taken into account. The model is composed of a set of coupled PDEs. A mathematical model based on a system of ODEs for Shiga 2 toxin neutralization by antibodies in the absence of cell is also studied. Both PDE and ODE systems are solved numerically. Numerical results are illustrated by figures and discussed.
KeywordsToxin Antibody Cell receptor Microtubule transport Molecular motors
Compliance with Ethical Standards
The authors declare that they have no competing interests.
- 3.Boerlin, P., McEwen, S.A., Boerlin-Petzold, F., Wilson, J.B., Johnson, R.P., Gyles, C.L.: Associations between virulence factors of Shiga toxin-producing Escherichia coli and disease in humans. J. Clin. Microbiol. 37, 497–503 (1999)Google Scholar
- 4.Griffin, P.M., Tauxe, R.V.: The epidemiology of infections caused by Escherichia coli O157:H7, other enterohemorrhagic E. coli, and the associated hemolytic uremic syndrome. Epidemiol. Rev. 13, 60–98 (1991)Google Scholar
- 5.Milford, D.V., Taylor, C.M., Guttridge, B., Hall, S.M., Rowe, B., Kleanthous, H.: Haemolytic uraemic syndromes in the British Isles 1985-8: association with verocytotoxin producing Escherichia coli. Part 1. Clinical and epidemiological aspects. Arch. Dis. Child 65, 716–721 (1990)CrossRefGoogle Scholar
- 7.Lingwood, C.A., Law, H., Richardson, S., Petric, M., Brunton, J.L., De Grandis, S., Karmali, M.: Glycolipid binding of purified and recombinant Escherichia coli produced verotoxin in vitro. J. Biol. Chem. 262, 8834–8839 (1987)Google Scholar
- 9.Sandvig, K., Van Deurs, B.: Endocytosis, intracellular transport, and cytotoxic action of Shiga toxin and ricin. Physiol. Rev. 76, 949–966 (1996)Google Scholar
- 12.Saxena, S.K., O’Brien, A.D., Ackerman, E.J.: Shiga toxin, Shiga-like toxin II variant, and ricin are all single-site RNA N-glycosidases of 28 S RNA when microinjected into Xenopus oocytes. J. Biol. Chem. 264, 596–601 (1989)Google Scholar
- 14.Sheoran, A.S., Chapman-Bonofiglio, B.R., Harvey, B.R., Mukherjee, J., Georgiou, G., Donohue-Rolfe, A., Tzipori, S.: Human antibody against Shiga toxin 2 administered to piglets after the onset of diarrhea due to Escherichia coli O157:H7 prevents fatal systemic complications. Infect. Immun. 73, 4607–4613 (2005)CrossRefGoogle Scholar
- 23.Alberts, B., Bray, D., Lewis, J., Raff, M., Roberts, K., Watson, J.D.: : Molecular Biology of the Cell, 3rd edn. Garland Publishing, New York (1994)Google Scholar
- 28.Truskey, G.A., Yuan, F., Katz, D.F.: Transport Phenomena in Biological Systems, 2nd edn. Pearson Prentice Hall Bioengineering (2009)Google Scholar
- 31.Nakajima, H., Kiyokawa, N., Katagiri, Y.U., Taguchi, T., Suzuki, T., Sekino, T., Mimori, K., Ebata, T., Saito, M., Nakao, H., Takeda, T., Fujimoto, J.: Kinetic analysis of binding between Shiga toxin and receptor glycolipid Gb3Cer by surface plasmon resonance. J. Biol. Chem. 276, 42915–42921 (2001)CrossRefGoogle Scholar