Identification of Salmonella typhi genes that are absent from Salmonella typhimurium and are expressed within macrophages
Abstract Text
Salmonella enterica serovar Typhi (S. typhi) is a host-adapted serovar that is specific for humans where it causes typhoid fever. Since there is no animal model to study S. typhi pathogenesis, little is known about virulence factors which are responsible for its ability to cause typhoid fever and its apparent adaptation to the human host. The virulence of other Salmonella serovars in animal models is also dependent on the abilities of these bacteria to survive within host macrophages. Our hypothesis is that S. typhi possesses unique genes, absent from S. typhimurium, a broad host serovar, that prevent survival or infection in the mouse. We have used selective capture of transcribed sequences (SCOTS) to identify S. typhi genes expressed during growth in human macrophages that were absent from S. typhimurium. This positive cDNA selection technique identified 36 distinct clones representing 17 DNA regions specific to S. typhi. Characterization of a 3.5 kb unique region, encoding for 3 putative ORFs, that were absent from S. typhimurium was undertaken. A markerless deletion of this unique region was accomplished by allelic exchange. The mutant and its complement will be tested for survival in human and murine-derived macrophage cell lines. This project has identified S. typhi-specific genes expressed during infection. Moreover, elucidation of the molecular basis of host specificity of S. typhi could lead to the development of an animal model that could be used for studying S. typhi pathogenesis and could be very useful for vaccine production using S. typhi as a vector for antigen delivery systems.
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