Identification of chitinase as a novel virulence factor for Listeria monocytogenes.

다국어 초록 (Multilingual Abstract)

<italic>Listeria monocytogenes</italic> is a food borne Gram positive pathogen that causes the disease listeriosis in humans and animals. <italic> L. monocytogenes</italic> has been the responsible for a number of food-borne outbreaks of listeriosis among humans. The disease caused by this bacterium can become very severe in immunocompromised people, often resulting in deaths.
<italic>L. monocytogenes</italic> is ubiquitious in nature, and is found in diverse ecological niches such as soil, water and natural vegetation. However, when this free living bacterium enters a mammalian host it often causes disease, and is therefore regarded as an environmental pathogen.
Environmental pathogens are those microorganisms that spend substantial parts of their life cycles outside their hosts, but can cause disease when they are inside the host. An important question about environmental pathogens is whether they are able to use molecules that are required for their survival outside the host, as virulence factors when they are inside their hosts. This hypothesis has come into the focus with the emergence of chitinases and chitin binding proteins as virulence factors in two other environmental pathogens, <italic> Legionella pneumophila</italic> and <italic>Vibrio cholerae.</italic> Chitinases are enzymes that hydrolyze chitin, which is a linear polymer of N-acetylglucosamine residues linked by (β1, 4) glycosidic bonds. Chitin is present in cell walls of algae and fungi; and in the exoskeletons of insects, mollusks, crustaceans and is the second most abundant organic compound on the earth. Bacterial chitinases and chitin binding proteins are supposed to be used for nutrient acquisition by utilizing chitin as a readily available source of carbon and nitrogen. However, with the works done on <italic>L. pneumophila</italic> and <italic> V. cholerae,</italic> it is evident that these pathogenic bacteria use chitinases and chitin binding proteins to enhance their survival in mammalian hosts as well.
The goal of this thesis is to find out whether <italic>L. monocytogenes </italic> uses its chitinase and chitin binding proteins for its survival inside animal models of infection. The thesis has two main parts. The first part will examine whether mutant strains of <italic>L. monocytogenes</italic> lacking chitinase and/or chitin binding proteins are attenuated in in vitro and in vivo models of infection. The second part of the thesis will examine the probable mechanisms by which chitinases of <italic>L. monocytogenes </italic> can be used by the bacterium to enhance its survival in the host.