Interaction of Bacillus Anthracis Exosporium Protein Bcla With Complement Factor H and Spore Persistence In The Lung

<p>Anthrax outbreaks in the United States and Europe and its potential use as a bioweapon have made <em>Bacillus anthracis</em> an interest of study. Anthrax infections are caused by the entry of <em>B. anthracis</em> spores into the host via the respiratory system, the gastrointestinal tract, cuts or wounds in the skin, and injection. Among these four forms, inhalational anthrax has the highest lethality rate and persistence of spores in the lungs of animals following pulmonary exposure has been noted for decades. However, details or mechanisms of spore persistence were not known. In this study, we investigated spore persistence in a mouse model. The results suggest that <em>B. anthracis</em> spores have special properties that promote persistence in the lung, and that there may be multiple mechanisms contributing to spore persistence. Moreover, recent discoveries from our laboratory suggest that spores evolved a sophisticated mechanism to interact with the host complement system. The complement system is a crucial part of the host defense mechanism against foreign microorganisms. Knowledge of the specific interactions that occur between the complement system and <em>B. anthracis</em> was limited. Studies performed in our laboratory have suggested that spores of <em>B. anthracis</em> can target specific proteins, such as Factor H (fH) of the complement system. Spores of <em>B. anthracis</em> are enclosed by an exosporium, which consists of a basal layer surrounded by a nap of hair-like filaments. The major structural component of the filaments is called <em>Bacillus</em> collagen-like protein of <em>anthracis </em>(BclA), which comprises a central collagen-like region and a globular C-terminal domain. BclA is the first point of contact with the innate system of an infected host. In this study, we investigated the molecular details of BclA-fH interaction with respect to the specific binding mechanism and the functional significance of this interaction in a murine model of anthrax infection. We hypothesized that the recruitment of fH to the spore surface by BclA limits the extent of complement activation and promotes pathogen survival and persistence in the infected host. Findings from this study are significant to understanding how to treat post-exposure prophylaxis and improve our knowledge of spores with the host immune system.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2013

Author dc:creator

• Jenkins, Sarah A

Contributors dc:contributor

• Yi Xu, PhD
• Magnus HÖÖk, PhD
• Rick A. Wetsel, PhD

• Bacillus anthracis
• spores
• persistence
• lung
• inhalational anthrax
• complement system
• BclA
• Factor H
• Biochemistry
• Immunology and Infectious Disease
• Medicine and Health Sciences
• Microbiology

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/344

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1376