Primary Involvement of Pharynx and Peyer's Patch in Inhalational and Intestinal Anthrax

Ian J Glomski,Alejandro Piris-Gimenez,Michel Huerre,Pierre L Goossens,Michèle Mock,John A T Young

doi:10.1371/journal.ppat.0030076

Ian J Glomski, Alejandro Piris-Gimenez + Show 4 more

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https://doi.org/10.1371/journal.ppat.0030076

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Abstract

Bacillus anthracis causes three forms of anthrax: inhalational, gastrointestinal, and cutaneous. Anthrax is characterized by both toxemia, which is caused by secretion of immunomodulating toxins (lethal toxin and edema toxin), and septicemia, which is associated with bacterial encapsulation. Here we report that, contrary to the current view of B. anthracis pathogenesis, B. anthracis spores germinate and establish infections at the initial site of inoculation in both inhalational and cutaneous infections without needing to be transported to draining lymph nodes, and that inhaled spores establish initial infection in nasal-associated lymphoid tissues. Furthermore, we found that Peyer's patches in the mouse intestine are the primary site of bacterial growth after intragastric inoculation, thus establishing an animal model of gastrointestinal anthrax. All routes of infection progressed to the draining lymph nodes, spleen, lungs, and ultimately the blood. These discoveries were made possible through the development of a novel dynamic mouse model of B. anthracis infection using bioluminescent non-toxinogenic capsulated bacteria that can be visualized within the mouse in real-time, and demonstrate the value of in vivo imaging in the analysis of B. anthracis infection. Our data imply that previously unrecognized portals of bacterial entry demand more intensive investigation, and will significantly transform the current perception of inhalational, gastrointestinal, and cutaneous B. anthracis pathogenesis.

Highlights

Bacillus anthracis is a sporulating Gram-positive bacterium that causes the disease anthrax
Anthrax is caused by Bacillus anthracis, a bacterial pathogen that forms spores, dormant bacteria that are highly resistant to destruction
We strove to determine in real space and time where and when spores introduced by these three routes of infection germinate and how bacteria subsequently disseminate in a mouse model

Summary

Introduction

Bacillus anthracis is a sporulating Gram-positive bacterium that causes the disease anthrax. The three forms of anthrax reflect the route by which the infection is initiated: cutaneous, gastrointestinal, and inhalational [1,2]. Gastrointestinal anthrax is generally considered to be the primary route of infection of livestock, can occur in humans, and is caused through the ingestion of contaminated food [2,11], yet the means by which B. anthracis crosses membrane barriers to establish infection remains unknown. The current model of inhalational anthrax consists of uptake of spores by alveolar macrophage, transport of these spores to the draining mediastinal lymph nodes, where the spores germinate and establish infection within the lymphatics to disseminate systemically [10,12,13]

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