Cargando…

The Potential Contributions of Lethal and Edema Toxins to the Pathogenesis of Anthrax Associated Shock

Outbreaks of Bacillus anthracis in the US and Europe over the past 10 years have emphasized the health threat this lethal bacteria poses even for developed parts of the world. In contrast to cutaneous anthrax, inhalational disease in the US during the 2001 outbreaks and the newly identified injectio...

Descripción completa

Detalles Bibliográficos
Autores principales: Hicks, Caitlin W., Cui, Xizhong, Sweeney, Daniel A., Li, Yan, Barochia, Amisha, Eichacker, Peter Q.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202877/
https://www.ncbi.nlm.nih.gov/pubmed/22069762
http://dx.doi.org/10.3390/toxins3091185
_version_ 1782215052592414720
author Hicks, Caitlin W.
Cui, Xizhong
Sweeney, Daniel A.
Li, Yan
Barochia, Amisha
Eichacker, Peter Q.
author_facet Hicks, Caitlin W.
Cui, Xizhong
Sweeney, Daniel A.
Li, Yan
Barochia, Amisha
Eichacker, Peter Q.
author_sort Hicks, Caitlin W.
collection PubMed
description Outbreaks of Bacillus anthracis in the US and Europe over the past 10 years have emphasized the health threat this lethal bacteria poses even for developed parts of the world. In contrast to cutaneous anthrax, inhalational disease in the US during the 2001 outbreaks and the newly identified injectional drug use form of disease in the UK and Germany have been associated with relatively high mortality rates. One notable aspect of these cases has been the difficulty in supporting patients once shock has developed. Anthrax bacilli produce several different components which likely contribute to this shock. Growing evidence indicates that both major anthrax toxins may produce substantial cardiovascular dysfunction. Lethal toxin (LT) can alter peripheral vascular function; it also has direct myocardial depressant effects. Edema toxin (ET) may have even more pronounced peripheral vascular effects than LT, including the ability to interfere with the actions of conventional vasopressors. Additionally, ET also appears capable of interfering with renal sodium and water retention. Importantly, the two toxins exert their actions via quite different mechanisms and therefore have the potential to worsen shock and outcome in an additive fashion. Finally, both toxins have the ability to inhibit host defense and microbial clearance, possibly contributing to the very high bacterial loads noted in patients dying with anthrax. This last point is clinically relevant since emerging data has begun to implicate other bacterial components such as anthrax cell wall in the shock and organ injury observed with infection. Taken together, accumulating evidence regarding the potential contribution of LT and ET to anthrax-associated shock supports efforts to develop adjunctive therapies that target both toxins in patients with progressive shock.
format Online
Article
Text
id pubmed-3202877
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-32028772011-11-08 The Potential Contributions of Lethal and Edema Toxins to the Pathogenesis of Anthrax Associated Shock Hicks, Caitlin W. Cui, Xizhong Sweeney, Daniel A. Li, Yan Barochia, Amisha Eichacker, Peter Q. Toxins (Basel) Review Outbreaks of Bacillus anthracis in the US and Europe over the past 10 years have emphasized the health threat this lethal bacteria poses even for developed parts of the world. In contrast to cutaneous anthrax, inhalational disease in the US during the 2001 outbreaks and the newly identified injectional drug use form of disease in the UK and Germany have been associated with relatively high mortality rates. One notable aspect of these cases has been the difficulty in supporting patients once shock has developed. Anthrax bacilli produce several different components which likely contribute to this shock. Growing evidence indicates that both major anthrax toxins may produce substantial cardiovascular dysfunction. Lethal toxin (LT) can alter peripheral vascular function; it also has direct myocardial depressant effects. Edema toxin (ET) may have even more pronounced peripheral vascular effects than LT, including the ability to interfere with the actions of conventional vasopressors. Additionally, ET also appears capable of interfering with renal sodium and water retention. Importantly, the two toxins exert their actions via quite different mechanisms and therefore have the potential to worsen shock and outcome in an additive fashion. Finally, both toxins have the ability to inhibit host defense and microbial clearance, possibly contributing to the very high bacterial loads noted in patients dying with anthrax. This last point is clinically relevant since emerging data has begun to implicate other bacterial components such as anthrax cell wall in the shock and organ injury observed with infection. Taken together, accumulating evidence regarding the potential contribution of LT and ET to anthrax-associated shock supports efforts to develop adjunctive therapies that target both toxins in patients with progressive shock. MDPI 2011-09-20 /pmc/articles/PMC3202877/ /pubmed/22069762 http://dx.doi.org/10.3390/toxins3091185 Text en © 2011 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Review
Hicks, Caitlin W.
Cui, Xizhong
Sweeney, Daniel A.
Li, Yan
Barochia, Amisha
Eichacker, Peter Q.
The Potential Contributions of Lethal and Edema Toxins to the Pathogenesis of Anthrax Associated Shock
title The Potential Contributions of Lethal and Edema Toxins to the Pathogenesis of Anthrax Associated Shock
title_full The Potential Contributions of Lethal and Edema Toxins to the Pathogenesis of Anthrax Associated Shock
title_fullStr The Potential Contributions of Lethal and Edema Toxins to the Pathogenesis of Anthrax Associated Shock
title_full_unstemmed The Potential Contributions of Lethal and Edema Toxins to the Pathogenesis of Anthrax Associated Shock
title_short The Potential Contributions of Lethal and Edema Toxins to the Pathogenesis of Anthrax Associated Shock
title_sort potential contributions of lethal and edema toxins to the pathogenesis of anthrax associated shock
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202877/
https://www.ncbi.nlm.nih.gov/pubmed/22069762
http://dx.doi.org/10.3390/toxins3091185
work_keys_str_mv AT hickscaitlinw thepotentialcontributionsoflethalandedematoxinstothepathogenesisofanthraxassociatedshock
AT cuixizhong thepotentialcontributionsoflethalandedematoxinstothepathogenesisofanthraxassociatedshock
AT sweeneydaniela thepotentialcontributionsoflethalandedematoxinstothepathogenesisofanthraxassociatedshock
AT liyan thepotentialcontributionsoflethalandedematoxinstothepathogenesisofanthraxassociatedshock
AT barochiaamisha thepotentialcontributionsoflethalandedematoxinstothepathogenesisofanthraxassociatedshock
AT eichackerpeterq thepotentialcontributionsoflethalandedematoxinstothepathogenesisofanthraxassociatedshock
AT hickscaitlinw potentialcontributionsoflethalandedematoxinstothepathogenesisofanthraxassociatedshock
AT cuixizhong potentialcontributionsoflethalandedematoxinstothepathogenesisofanthraxassociatedshock
AT sweeneydaniela potentialcontributionsoflethalandedematoxinstothepathogenesisofanthraxassociatedshock
AT liyan potentialcontributionsoflethalandedematoxinstothepathogenesisofanthraxassociatedshock
AT barochiaamisha potentialcontributionsoflethalandedematoxinstothepathogenesisofanthraxassociatedshock
AT eichackerpeterq potentialcontributionsoflethalandedematoxinstothepathogenesisofanthraxassociatedshock