Mentor: Rimi Chowdhry, Ph.D.

Enteric pathogens regulate the expression of their virulence and proliferation genes through the recognition and exploitation of environmental metabolites. Pathogens utilize such compounds to increase or decrease transcription of virulence genes, allowing them to choose between energetically expensive virulence programs or gut proliferation based on surrounding conditions. This practice is crucial for pathogen success as it prevents spending valuable resources on invasion genes before optimal population levels and growth conditions are met, while minimizing damage from a host immune response.

The bacterial pathogen Shigella flexneri is one example of such masterful use of metabolites. We hypothesized that S. flexneri can utilize intestinal fatty acids as signals to regulate a critical step in the infection strategy: cell-to-cell spread. This movement between colon epithelial cells is mediated by icsA, activated by master transcriptional regulator VirF, which has itself been shown to be repressed by fatty acids. Here we show that dietary and microbially sourced fatty acids can be exploited by S. flexneri to reduce the expression of icsA and hence cell-to-cell spread.

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