Exploring the Genetic Factors Contributing to Resistance and Susceptibility of Listeria Monocytogenes to Phagosome-Mediated Killing
Listeria monocytogenes is a facultative intracellular pathogen that causes disease in immunocompromised individuals and pregnant women. Its life cycle is well characterized. The pathogen enters phagocytes of the immune system, including macrophages and dendritic cells. As seen from in vitro studies using macrophages, upon entry into phagocytes L. monocytogenes escapes the vacuole and grows in the cytosol thus avoiding phagosome-mediated killing. Mutants of L. monocytogenes in which the Listeriolysin O (LLO) gene has been deleted lack the ability to escape the phagosome into the host cell cytoplasm and are avirulent, suggesting that they die in the phagosome. Furthermore, these mutants are unable to induce adaptive immunity in the host. I hypothesize that L. monocytogenes does have to cope with initial phagosome stress before escape from the phagosome. Our current understanding of the amount of phagosome stress encountered in vivo is not complete, but it appears that L. monocytogenes may be able to survive some initial phagosome-mediated stress before it escapes the phagosome.
I am interested in studying the genetic factors that contribute to both the resistance and susceptibility of L. monocytogenes to phagosome-mediated killing. This summer I will characterize L. monocytogenes mutants that were recently found to survive longer in the cell phagosome. I will also conduct my own unbiased forward genetic screen to identify new mutants that survive phagosomal stress. This approach should reveal the genetic basis used by L. monocytogenes for coping with the stress encountered in the harsh environment of the phagosome. The project has the potential to give us better understanding of the phagosome microbe interaction and to shed light upon how pathogens cope with stressors in the host cell.
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- Major: Molecular Environmental Biology, Global Studies, Anthropology and Minor in Global Public Health
- Mentor: Daniel Portnoy