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Content archived on 2024-05-24

Quorum sensing and regulation of virulence factors in salmonella infection

Objective

The human pathogen Salmonella remains a significant ongoing threat to worldwide public health. Although major advances have been made with respect to the understanding of Salmonella-specific host pathogen interaction, the nature and the regulation of bacterial virulence effectors directly responsible for the host response remains elusive. Quorum sensing constitutes a bacterial cell-cell communication system in which bacterial secreted auto-inducing molecules signal and trigger changes in gene expression. Such systems can act as global regulators of virulence like in Staphylococcus aureus. In Salmonella typhimurium, the quorum sensing auto-inducer AI-2 is the final product in a biosynthetic pathway involving the AI-2 synthesis encoded by the luxS gene. Recent reports indicate that AI-2 plays a role in the coordination of virulence in Escherichia coli and Streptococcus pyogenes . However , the role of quorum sensing mechanisms in Salmonella pathogenicity has not been investigated yet. With this project, I intend to explore the role of AI-2 in regulating Salmonella virulence. A luxS-null mutant will be constructed and compared with the parent in its ability to infect and colonize the host by using cultured human epithelial intestinal cells, cultured mouse macrophages and a mouse model of systemic infection. Effects of AI-2 in regulating expression of Salmonella pathogenicity islands (SPI-1 and SPI-2)-encoded virulence factors including the components of the type III secretion systems will be analyzed in vitro and in vivo. Finally, the function of AI-2 as a regulator involved directly in infection and stimulation of host signaling cascades will be studied.

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