The Potential Pathogenic Contributions of Endothelial Barrier and Arterial Contractile Dysfunction to Shock Due to B. anthracis Lethal and Edema Toxins

Shock with B. anthracis infection is particularly resistant to conventional cardiovascular support and its mortality rate appears higher than with more common bacterial pathogens. As opposed to many bacteria that lack exotoxins directly depressing hemodynamic function, lethal and edema toxin (LT and...

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Main Authors: Dante A. Suffredini, Xizhong Cui, Wanying Xu, Yan Li, Peter Q. Eichacker
Format: Article
Language:English
Published: MDPI AG 2017-12-01
Series:Toxins
Subjects:
Online Access:https://www.mdpi.com/2072-6651/9/12/394
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spelling doaj-2e0b7d74133944188d7438c57d470e992020-11-24T22:04:12ZengMDPI AGToxins2072-66512017-12-0191239410.3390/toxins9120394toxins9120394The Potential Pathogenic Contributions of Endothelial Barrier and Arterial Contractile Dysfunction to Shock Due to B. anthracis Lethal and Edema ToxinsDante A. Suffredini0Xizhong Cui1Wanying Xu2Yan Li3Peter Q. Eichacker4Critical Care Medicine Department, Clinical Center, National Institutes of Health, Building 10, Room 2C145, 9000 Rockville Pike, Bethesda, MD 20892, USACritical Care Medicine Department, Clinical Center, National Institutes of Health, Building 10, Room 2C145, 9000 Rockville Pike, Bethesda, MD 20892, USACritical Care Medicine Department, Clinical Center, National Institutes of Health, Building 10, Room 2C145, 9000 Rockville Pike, Bethesda, MD 20892, USACritical Care Medicine Department, Clinical Center, National Institutes of Health, Building 10, Room 2C145, 9000 Rockville Pike, Bethesda, MD 20892, USACritical Care Medicine Department, Clinical Center, National Institutes of Health, Building 10, Room 2C145, 9000 Rockville Pike, Bethesda, MD 20892, USAShock with B. anthracis infection is particularly resistant to conventional cardiovascular support and its mortality rate appears higher than with more common bacterial pathogens. As opposed to many bacteria that lack exotoxins directly depressing hemodynamic function, lethal and edema toxin (LT and ET respectively) both cause shock and likely contribute to the high lethality rate with B. anthracis. Selective inhibition of the toxins is protective in infection models, and administration of either toxin alone in animals produces hypotension with accompanying organ injury and lethality. Shock during infection is typically due to one of two mechanisms: (i) intravascular volume depletion related to disruption of endothelial barrier function; and (ii) extravasation of fluid and/or maladaptive dilation of peripheral resistance arteries. Although some data suggests that LT can produce myocardial dysfunction, growing evidence demonstrates that it may also interfere with endothelial integrity thereby contributing to the extravasation of fluid that helps characterize severe B. anthracis infection. Edema toxin, on the other hand, while known to produce localized tissue edema when injected subcutaneously, has potent vascular relaxant effects that could lead to pathologic arterial dilation. This review will examine recent data supporting a role for these two pathophysiologic mechanisms underlying the shock LT and ET produce. Further research and a better understanding of these mechanisms may lead to improved management of B. anthracis in patients.https://www.mdpi.com/2072-6651/9/12/394B. anthracisshockendothelial permeabilityarterial contractile dysfunction
collection DOAJ
language English
format Article
sources DOAJ
author Dante A. Suffredini
Xizhong Cui
Wanying Xu
Yan Li
Peter Q. Eichacker
spellingShingle Dante A. Suffredini
Xizhong Cui
Wanying Xu
Yan Li
Peter Q. Eichacker
The Potential Pathogenic Contributions of Endothelial Barrier and Arterial Contractile Dysfunction to Shock Due to B. anthracis Lethal and Edema Toxins
Toxins
B. anthracis
shock
endothelial permeability
arterial contractile dysfunction
author_facet Dante A. Suffredini
Xizhong Cui
Wanying Xu
Yan Li
Peter Q. Eichacker
author_sort Dante A. Suffredini
title The Potential Pathogenic Contributions of Endothelial Barrier and Arterial Contractile Dysfunction to Shock Due to B. anthracis Lethal and Edema Toxins
title_short The Potential Pathogenic Contributions of Endothelial Barrier and Arterial Contractile Dysfunction to Shock Due to B. anthracis Lethal and Edema Toxins
title_full The Potential Pathogenic Contributions of Endothelial Barrier and Arterial Contractile Dysfunction to Shock Due to B. anthracis Lethal and Edema Toxins
title_fullStr The Potential Pathogenic Contributions of Endothelial Barrier and Arterial Contractile Dysfunction to Shock Due to B. anthracis Lethal and Edema Toxins
title_full_unstemmed The Potential Pathogenic Contributions of Endothelial Barrier and Arterial Contractile Dysfunction to Shock Due to B. anthracis Lethal and Edema Toxins
title_sort potential pathogenic contributions of endothelial barrier and arterial contractile dysfunction to shock due to b. anthracis lethal and edema toxins
publisher MDPI AG
series Toxins
issn 2072-6651
publishDate 2017-12-01
description Shock with B. anthracis infection is particularly resistant to conventional cardiovascular support and its mortality rate appears higher than with more common bacterial pathogens. As opposed to many bacteria that lack exotoxins directly depressing hemodynamic function, lethal and edema toxin (LT and ET respectively) both cause shock and likely contribute to the high lethality rate with B. anthracis. Selective inhibition of the toxins is protective in infection models, and administration of either toxin alone in animals produces hypotension with accompanying organ injury and lethality. Shock during infection is typically due to one of two mechanisms: (i) intravascular volume depletion related to disruption of endothelial barrier function; and (ii) extravasation of fluid and/or maladaptive dilation of peripheral resistance arteries. Although some data suggests that LT can produce myocardial dysfunction, growing evidence demonstrates that it may also interfere with endothelial integrity thereby contributing to the extravasation of fluid that helps characterize severe B. anthracis infection. Edema toxin, on the other hand, while known to produce localized tissue edema when injected subcutaneously, has potent vascular relaxant effects that could lead to pathologic arterial dilation. This review will examine recent data supporting a role for these two pathophysiologic mechanisms underlying the shock LT and ET produce. Further research and a better understanding of these mechanisms may lead to improved management of B. anthracis in patients.
topic B. anthracis
shock
endothelial permeability
arterial contractile dysfunction
url https://www.mdpi.com/2072-6651/9/12/394
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