Characterization of Listeria monocytogenes growth and colonization of the murine gallbladder

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Abstract/Contents

Abstract
Listeria monocytogenes is a facultative intracellular pathogen that causes severe invasive disease in susceptible populations. Using in vivo bioluminescent imaging, it was recently discovered that this bacterium can colonize the murine gallbladder of otherwise asymptomatic mice. This finding was surprising as L. monocytogenes, after invasion of the intestines, was thought to survive only intracellularly in an infected host and in the gallbladder the bacteria lived extracellularly. It was also surprising that a bacterium could grow and replicate in the pure bile environment of the gallbladder lumen as bile is a potent antimicrobial compound. In this study, we characterized how Listeria monocytogenes is able to reach the gallbladder during infection and examined how this pathogen is able to survive in this environment. Using a mouse adapted L. monocytogenes which expresses a modified InlA capable of binding murine E-cadherin we were able to follow the kinetics of gallbladder colonization after oral infection using in vivo bioluminescent imaging. We then utilized surgical manipulation of the mouse host and repeated the oral infection to determine how L. monocytogenes reaches the gallbladder. Once we had determined the mechanism of gallbladder entry, we then utilized whole genome microarrays to characterize the transcriptome of L. monocytogenes during in vivo growth in the gallbladder and in freshly isolated murine bile. Finally, we attempted to determine what nutrients are utilized by L. monocytogenes during growth in bile and looked at the ability of other bacterial species to grow in this environment. Through these experiments we demonstrated regular asymptomatic gallbladder colonization by L. monocytogenes after oral infection and that L. monocytogenes reaches the gallbladder via the hepatic duct only after first causing systemic infection and escaping the liver. We also demonstrated that the lifestyle in the gallbladder is similar to that in the intestine with the exception of the need for bile resistance genes, and finally that it appears as though simple carbon sources may be utilized during bile growth and that bile may not be as toxic to bacteria as has been thought. Our work suggests that gallbladder colonization may not be exclusive to only L. monocyctogenes and Salmonella Typhi since other bacteria can grow, and in some cases better than L. monocyctogenes, in pure bile.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Copyright date 2011
Publication date 2010, c2011; 2010
Issuance monographic
Language English

Creators/Contributors

Associated with Eimerman, Patrick Ryan
Associated with Stanford University, Department of Microbiology and Immunology
Primary advisor Contag, Christopher H
Thesis advisor Contag, Christopher H
Thesis advisor Amieva, Manuel
Thesis advisor Boothroyd, John C
Thesis advisor Wandless, Thomas
Advisor Amieva, Manuel
Advisor Boothroyd, John C
Advisor Wandless, Thomas

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Patrick Ryan Eimerman.
Note Submitted to the Department of Microbiology and Immunology.
Thesis Thesis (Ph.D.)--Stanford University, 2011.
Location electronic resource

Access conditions

Copyright
© 2011 by Patrick Ryan Eimerman
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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