Anthrax toxin: pathologic effects on the cardiovascular system.
Anthrax is a disease caused by infection with spores from the bacteria Bacillus anthracis. After entering the body, the spores germinate into bacteria and secrete a toxin that causes local edema and, in systemic infections, cardiovascular collapse and death. The toxin is a tripartite polypeptide, consisting of protective antigen (PA), lethal factor (LF) and edema factor (EF), which have key roles in the bacterial pathogenesis and disease progression. PA facilitates transfer of LF and EF to the cytosol. Lethal toxin is a zinc metalloproteinase, which has the capacity to inactivate mitogen-activated protein (MAP) kinase kinase (MEK) and stimulates the release of sepsis-related cytokines tumor necrosis factor-alpha and interleukin-1beta. Edema factor is a calmodulin (CaM)-dependent adenylate cyclase, which increases levels of cyclic AMP, causing impaired neutrophil function and disruption of water balance that ultimately results in massive tissue edema. Together, the toxins effectively inhibit host innate and adaptive immune responses, allowing the bacteria to grow unrestrained and overwhelming any resistance. Clinically, inhalational anthrax presents in a biphasic pattern with initial nonspecific "flu-like" symptoms nausea and vomiting 1 to 4 days after exposure, followed by severe illness with dyspnea, high fever and circulatory shock. The latter symptoms represent a terminal stage and treatment is often ineffective when started at that time. Key indicators of early anthrax cardiovascular-related pathogenesis include mediastinal widening in association with pleural effusion and edema. In this review, we describe the current understanding of anthrax toxins on cellular function in the context of cardiovascular function and discuss potential therapeutic strategies.
Golden
Honey B
HB
Division of Molecular Cardiology, Cardiovascular Research Institute, The Texas A and M University System Health Science Center, College of Medicine, Scott and White, Baylor College of Dentistry, The Texas A and M Health Science Center, Dallas, TX, USA.
Watson
Linley E
LE
Lal
Hind
H
Verma
Suresh K
SK
Foster
Donald M
DM
Kuo
Shu-Ru
SR
Sharma
Avadhesh
A
Frankel
Arthur
A
Dostal
David E
DE
D000881:Anthrax / Q000503:physiopathology / Q000628:therapy; D000942:Antigens, Bacterial / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D001427:Bacterial Toxins / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D002319:Cardiovascular System / Q000187:drug effects*; D006801:Humans
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin