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Chronicles of a pathogen’s lifestyle: from a single cell to a population

Abstract

Bacterial cells are amongst the simplest forms of life. Nevertheless, explaining a cell’s behavior still represents a challenge that the scientific community is grappling with. In this dissertation, I disentangle multiple layers of interacting dynamic complex systems that govern the bacterial response including: 1) the metabolic network, 2) the genetic background, and 3) the nutritional environment. I start by implementing a traditional methodology for the deep metabolic characterization of a single strain of \textit{S. aureus}, by reconstructing its metabolic network, and proceed to elucidate how this network governs its metabolic response as a result of a changing nutritional environment. Next, I leverage the deluge in genomic sequence data to propagate knowledge from deeply characterized Gram-negative strains including \textit{S. enterica} to multiple closely related strains, linking genotypic variations to diverging phenotypes, and diverging phenotypes to bacterial lifestyle. Finally, I demonstrate how information inherent to small genomic deviations can reveal the impact of long term colonization on bacterial evolution.

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