Skip to Main Content
 

Global Search Box

 
 
 
 

ETD Abstract Container

Abstract Header

The Importance of Listeriolysin O in Host Cell Invasion by Listeria monocytogenes and its Use in Vaccine Development

Abstract Details

2019, Doctor of Philosophy, Ohio State University, Microbiology.

Listeria monocytogenes is a facultative intracellular pathogen and the etiological agent of the life-threatening disease listeriosis. L. monocytogenes is ubiquitous in the environment and frequently contaminates food products, including beef, poultry, vegetables, dairy products, and particularly ready-to-eat foods. Because L. monocytogenes can grow under conditions that are typically used for food preservation, including low temperatures and high salt concentrations, preventing contamination and effectively sanitizing food production equipment is both costly and difficult. Consumption of contaminated food by otherwise healthy adults usually results in minor cases of noninvasive listeriosis that do not require treatment. However, particularly susceptible populations including pregnant women, the elderly, and those with compromised immune systems can develop severe invasive listeriosis in which the bacteria can cross the intestinal barrier to infect the liver, spleen, and ultimately the central nervous system, as well as the placenta, in the case of pregnant women.

L. monocytogenes has the ability to invade and replicate within a wide variety of phagocytic and nonphagocytic cells. L. monocytogenes has been known to use two major invasion factors to enter nonphagocytic cells, InlA and InlB. After endocytosis of the bacterium, L. monocytogenes disrupts the vacuole and enters the host cell cytosol using the pore-forming toxin, listeriolysin O (LLO). In the cytosol, the bacterium replicates and spreads to adjacent cells.

Though InlA and InlB have been considered the primary invasion factors, LLO was recently identified as an additional factor in the invasion of hepatocytes. Importantly, during infection, all three of these factors are co-expressed and have the potential to act in concert with one another. In our work, for the first time, we demonstrate the relative roles and importance of LLO, InlA, and InlB during host cell invasion. LLO is an important invasin in a variety of hepatocytes, but not placental cells, or endothelial cells, and cooperates with InlA to potentiate invasion. In addition to promoting invasion of enterocytes, InlA also promotes association with human hepatocytes and placental cells. We identified no role for InlB initially. We only observed a role for this factor when we introduced a constitutively active transcription regulator PrfA*, suggesting that InlB may not be as critical to host cell invasion in strains with properly regulated virulence regulon expression.

In light of the importance of LLO during infection, we have developed a vaccine that uses an LLO toxoid variant (LLOT) as an antigen and cholera toxin as an adjuvant. We found that this vaccine leads to anti-LLO antibody production and the development of a Th1 type immune response. Protection in the intravenous, non-pregnant murine model appears to be independent of anti-LLO antibodies in the context of full functional T cell response.

Stephanie Seveau, Ph.D. (Advisor)
Prosper Boyaka, Ph.D. (Committee Member)
John Gunn, Ph.D. (Committee Member)
Chad Rappleye, Ph.D. (Committee Member)
129 p.

Recommended Citations

Citations

  • Phelps, C. (2019). The Importance of Listeriolysin O in Host Cell Invasion by Listeria monocytogenes and its Use in Vaccine Development [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1555582881156988

    APA Style (7th edition)

  • Phelps, Christopher. The Importance of Listeriolysin O in Host Cell Invasion by Listeria monocytogenes and its Use in Vaccine Development. 2019. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1555582881156988.

    MLA Style (8th edition)

  • Phelps, Christopher. "The Importance of Listeriolysin O in Host Cell Invasion by Listeria monocytogenes and its Use in Vaccine Development." Doctoral dissertation, Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1555582881156988

    Chicago Manual of Style (17th edition)