Current understanding of Bacillus anthracis toxin molecules organization and approaches for blocking their cytotoxic action

Here, we review the data on mechanisms inhibiting cytotoxic effect of anthrax toxin on the immune system cells. Various disease forms, immunopathogenesis and contemporary methods for anthrax treatment are discussed. In addition, an anthrax toxin was outlined, whereas structural and functional organi...

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Autores principales:	V. V. Firstova, I. G. Shemyakin, I. A. Dyatlov
Formato:	article
Lenguaje:	RU
Publicado:	Sankt-Peterburg : NIIÈM imeni Pastera 2020
Materias:	b. anthracis protective antigen lethal factor edema factor toxin immunopathogenesis Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/4a376f50f66641bb8895bee6f747be03
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spelling	oai:doaj.org-article:4a376f50f66641bb8895bee6f747be032021-11-22T07:09:53ZCurrent understanding of Bacillus anthracis toxin molecules organization and approaches for blocking their cytotoxic action2220-76192313-739810.15789/2220-7619-2019-5-6-639-647https://doaj.org/article/4a376f50f66641bb8895bee6f747be032020-02-01T00:00:00Zhttps://www.iimmun.ru/iimm/article/view/721https://doaj.org/toc/2220-7619https://doaj.org/toc/2313-7398Here, we review the data on mechanisms inhibiting cytotoxic effect of anthrax toxin on the immune system cells. Various disease forms, immunopathogenesis and contemporary methods for anthrax treatment are discussed. In addition, an anthrax toxin was outlined, whereas structural and functional organization of the protective antigen, lethal and edema factors was detailed. A mechanism for association of a protective antigen and lethal factor, protective antigen and edema factor leading to formation of a lethal toxin and edema toxin, respectively, was described. Participation of protective antigen domains in the process of interaction with surface receptors of imunocompetent cells as well as features of binding a protective antigen with lethal factor and edema factor are discussed. A mechanism of endosomal toxin complex internalization and subsequent transfer of effector molecules to the cytosol are described. Effects of the lethal factor and the edema factor on components of eukaryotic cells as well as cytotoxicity mechanisms are analyzed. The approaches to block anthrax toxin action at various stages of toxicoemia have been analyzed based on previously uncovered sequential signs of cytotoxic activity for Bacillus anthracis toxins. Currently available chimeric and humanized monoclonal antibodies are capable of neutralizing B. anthracis toxins at diverse assembly stages, particularly considering the drugs inhibiting: inter-receptor interaction between protective antigen with eukaryotic cells; furin-like enzymes activating prepore assembly; protective antigen oligomerization; binding of the lethal factor or edema factor to the protective antigen; translocation of the lethal factor or the edema factor into cell cytosol; transport of protective antigen with lethal factor or edema factor from endosomes; enzymatic activity of lethal factor or edematous factor. The anti-toxin agents approved for anthrax prevention and treatment in Russia and worldwide are discussed. The limitations of anti-toxin agents and perspectives for their improvement are also described including inhibition of lethal factor activity, interference with integration of toxin components, blockade of interactions between toxic complexes and immune cell receptors.V. V. FirstovaI. G. ShemyakinI. A. DyatlovSankt-Peterburg : NIIÈM imeni Pasteraarticleb. anthracisprotective antigenlethal factoredema factortoxinimmunopathogenesisInfectious and parasitic diseasesRC109-216RUInfekciâ i Immunitet, Vol 9, Iss 5-6, Pp 639-647 (2020)
institution	DOAJ
collection	DOAJ
language	RU
topic	b. anthracis protective antigen lethal factor edema factor toxin immunopathogenesis Infectious and parasitic diseases RC109-216
spellingShingle	b. anthracis protective antigen lethal factor edema factor toxin immunopathogenesis Infectious and parasitic diseases RC109-216 V. V. Firstova I. G. Shemyakin I. A. Dyatlov Current understanding of Bacillus anthracis toxin molecules organization and approaches for blocking their cytotoxic action
description	Here, we review the data on mechanisms inhibiting cytotoxic effect of anthrax toxin on the immune system cells. Various disease forms, immunopathogenesis and contemporary methods for anthrax treatment are discussed. In addition, an anthrax toxin was outlined, whereas structural and functional organization of the protective antigen, lethal and edema factors was detailed. A mechanism for association of a protective antigen and lethal factor, protective antigen and edema factor leading to formation of a lethal toxin and edema toxin, respectively, was described. Participation of protective antigen domains in the process of interaction with surface receptors of imunocompetent cells as well as features of binding a protective antigen with lethal factor and edema factor are discussed. A mechanism of endosomal toxin complex internalization and subsequent transfer of effector molecules to the cytosol are described. Effects of the lethal factor and the edema factor on components of eukaryotic cells as well as cytotoxicity mechanisms are analyzed. The approaches to block anthrax toxin action at various stages of toxicoemia have been analyzed based on previously uncovered sequential signs of cytotoxic activity for Bacillus anthracis toxins. Currently available chimeric and humanized monoclonal antibodies are capable of neutralizing B. anthracis toxins at diverse assembly stages, particularly considering the drugs inhibiting: inter-receptor interaction between protective antigen with eukaryotic cells; furin-like enzymes activating prepore assembly; protective antigen oligomerization; binding of the lethal factor or edema factor to the protective antigen; translocation of the lethal factor or the edema factor into cell cytosol; transport of protective antigen with lethal factor or edema factor from endosomes; enzymatic activity of lethal factor or edematous factor. The anti-toxin agents approved for anthrax prevention and treatment in Russia and worldwide are discussed. The limitations of anti-toxin agents and perspectives for their improvement are also described including inhibition of lethal factor activity, interference with integration of toxin components, blockade of interactions between toxic complexes and immune cell receptors.
format	article
author	V. V. Firstova I. G. Shemyakin I. A. Dyatlov
author_facet	V. V. Firstova I. G. Shemyakin I. A. Dyatlov
author_sort	V. V. Firstova
title	Current understanding of Bacillus anthracis toxin molecules organization and approaches for blocking their cytotoxic action
title_short	Current understanding of Bacillus anthracis toxin molecules organization and approaches for blocking their cytotoxic action
title_full	Current understanding of Bacillus anthracis toxin molecules organization and approaches for blocking their cytotoxic action
title_fullStr	Current understanding of Bacillus anthracis toxin molecules organization and approaches for blocking their cytotoxic action
title_full_unstemmed	Current understanding of Bacillus anthracis toxin molecules organization and approaches for blocking their cytotoxic action
title_sort	current understanding of bacillus anthracis toxin molecules organization and approaches for blocking their cytotoxic action
publisher	Sankt-Peterburg : NIIÈM imeni Pastera
publishDate	2020
url	https://doaj.org/article/4a376f50f66641bb8895bee6f747be03
work_keys_str_mv	AT vvfirstova currentunderstandingofbacillusanthracistoxinmoleculesorganizationandapproachesforblockingtheircytotoxicaction AT igshemyakin currentunderstandingofbacillusanthracistoxinmoleculesorganizationandapproachesforblockingtheircytotoxicaction AT iadyatlov currentunderstandingofbacillusanthracistoxinmoleculesorganizationandapproachesforblockingtheircytotoxicaction
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Current understanding of Bacillus anthracis toxin molecules organization and approaches for blocking their cytotoxic action

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