For hundreds of millions of years, have been regulating very similar developmental patterning or cell-type-specific properties during development – a striking NVP-BKM120 example of which is the conservation of GRH family function with respect to epithelial barrier formation in animals. It may be that the functions of animal transcription factors are somewhat more evolutionarily constrained than those of Fungi, and that Fungi are more likely to evolve new combinations of transcription factors to regulate core biological functions. As the world continues to focus on many recent findings concerning the pathogenic and adaptive mechanisms of foodborne S. Typhimurium and S. Enteritidis, the principal factors underlying the unique epidemiological pattern and disease manifestation of this virulent, human-restricted, intracellular pathogen, S. Typhi, remains intruiging. In recent years, increasing evidence has implicated carbon catabolism as a virulence determinant of human pathogens. The ability of pathogenic bacteria to metabolize various nutrients, especially carbon sources, is essential for the invasion, growth, survival and colonisation in intestinal and extra-intestinal sites in their hosts. To successfully colonise and persist in the various niches within the host during the course of infection, bacterial pathogens need to adjust and adapt their metabolic activity to the local nutrient availability. Nonetheless, as compared with the growing knowledge of molecular bacterial virulence and pathogenesis, research on pathogenic bacterial metabolism and persistence in the human host has progressed very little. S. Typhi exhibits unique characteristics as an intracellular human pathogen that are not observed in other human bacterial pathogens: it is human host restricted and incapable of infecting other living organisms; able to cause both acute and chronic infection, displaying various disease manifestations; and able to transform the human host into long-term asymptomatic carriage in the environment with periodical dissemination via urine and faeces. Therefore, it is important to understand the intracellular lifestyle of this unique pathogen. To do so, we employed highthroughput phenotypic microarray analysis to characterise the carbon metabolic capacity of S. Typhi in the human host. The novelty of this study is derived from the interesting and diverse background of each of the S. Typhi strains included in this work. These S. Typhi strains were carefully selected to include strains from Malaysia and Chile to determine whether there were any metabolic differences between the two areas of typhoid endemicity which are distantly separated. To explore our hypothesis that the metabolic capacity of the strains isolated from stool develops an adaptive persistence mechanism in the liver or gallbladder during chronic infection, these stool strains will differ from the strains isolated from the blood during acute systemic infection in the human host. A bacterial strain originated from a healthy human carrier was included in this study to contrast with the strains of transient chronic infection. The occurrence of S. Typhi in the environment is extremely rare, even though it is generally accepted that the pathogen could be transmitted via contaminated water and foods.