Pathology of Inhalational Anthrax Animal Models

Twenhafel, Nancy

doi:10.1177/0300985810378112

Cited by 82 publications

(94 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast to the Moayeri hypoxia study, necropsies from B. anthracis infections show fibrin deposits and vasculitis in several animal models [96]. What is striking is that the bacilli can reach such high numbers in hosts before there are any overt signs of morbidity.…”

Section: Cardiovascular and Endothelial Effectsmentioning

confidence: 70%

“…This peptide-based capsule is atypical from other bacterial capsules, including many of those in Bacillaceae [17,82]. The capsule is considered a major virulence factor, as infection with a capsule deficient strain has drastically reduced mortality in most hosts, yet it remains poorly studied compared to the exotoxin [93][94][95][96]. The capsule is thought to act to prevent phagocytosis, but more recent studies have suggested that the capsule also interacts with the exotoxin to increase virulence [97,98].…”

Section: The Vegetative Bacillimentioning

confidence: 99%

“…The major virulence factors of B. anthracis are the exotoxin and the capsule [95,96,103,104]. The exotoxin will be further discussed in the next section due to the wealth of research on its role in infection.…”

Section: The Vegetative Bacillimentioning

confidence: 99%

“…Increased leakage or hemorrhage of the vasculature is commonly associated with anthrax in non-human primate models [96]. Treatment of primary human endothelial monolayers with purified LT, but not its individual components, increases the permeability in a concentration and time dependent manner [252].…”

Section: Cardiovascular and Endothelial Effectsmentioning

confidence: 99%

“…Observations from several studies noted that bacilli were rarely found within the alveolar spaces of the lungs, but spores and germinated bacilli were often found in macrophages and the lung associated lymph nodes [74,95,266,267,272,274]. Additionally, inhalational anthrax does not cause broncheopneumonia like several other lung pathogens, but an interstitial pneumonia with pathological evidence that it is secondary to dissemination [96,267,272]. Histological analysis of guinea pigs infected intratracheally with B. anthracis spores suggested that phagocytes could act as a vehicle to deliver spores or vegetative bacilli to the draining mediastinal lymph nodes [74].…”

Section: Phagocyte Mediated Dissemination To Lymphatic Tissuementioning

confidence: 99%

See 4 more Smart Citations

Opening moves: early events in anthrax pathogenesis and their consequences for dissemination

Lowe

View full text Add to dashboard Cite

Bacillus anthracis is a Gram positive sporulating bacterium that is the causative agent of anthrax. Early steps in dissemination are understudied due to the asymptomatic and asynchronous nature of B. anthracis infections. The goals of these studies are to establish a model of the early steps of B. anthracis infections and examine how the initial site of infection and exotoxin production affect bacterial dissemination. In these studies, a mouse model was used in combination with a bioluminescent signature tagged library to determine how B.anthracis disseminates through the host and the roles of an exotoxin component, lethal factor, in colonization and dissemination. This library allowed for real time observation of dissemination and analysis of bacterial population dynamics. In the first set of experiments, mice were infected via inhalational or subcutaneous routes with the tagged library to determine how the bacterial population changed during dissemination. In inhalational and subcutaneous infections, the disseminated population was comprised of a small subset of the original library.This indicated the presence of a population bottleneck, a random decrease in genetic diversity during the infection. Surprisingly, the diminishment and location of the bottleneck varied depending on the initial site of infection. This suggested B. anthracis exploits multiple host environments and some sites may be more permissive for dissemination than others. In the second set of experiments, mice were infected with a signature tagged library where a portion of clones lacked lethal factor. Lethal factor is known to be an important virulence factor as deletion results in attenuated or complete loss of virulence in most animal models. Host survival increased when < 10% of the library produced lethal factor, but few other differences were observed. Furthermore, decreases in the proportion of lethal factor producing clones led to fewer clones disseminating. These findings suggest that a threshold of lethal factor must be ii produced for colonization and dissemination to occur in vivo. In total, this work provides an understanding of how B. anthracis is able to rapidly disseminate from a several tissues and gives insights in where future therapeutics should be focused to reduce disease incidence.iii

show abstract

Section: Cardiovascular and Endothelial Effectsmentioning

confidence: 70%