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Salmonella typhi , the etiologic agent of typhoid fever, is adapted to the human host and unable to infect nonprimate species. The genetic basis for host specificity inS. typhi is unknown. The avirulence ofS. typhi in animal hosts may result from a lack of genes present in the broad-host-range pathogenSalmonella typhimurium . Genomic subtractive hybridization was successfully employed to isolateS. typhimurium genomic sequences which are absent from theS. typhi genome. These genomic subtracted sequences mapped to 17 regions distributed throughout theS. typhimurium chromosome. A positive cDNA selection method was then used to identify subtracted sequences which were transcribed byS. typhimurium following macrophage phagocytosis. A novel putative transcriptional regulator of the LysR family was identified as transcribed by intramacrophageS. typhimurium . This putative transcriptional regulator was absent from the genomes of the human-adapted serovarsS. typhi andSalmonella paratyphi A. Mutations within this gene did not alter the level ofS. typhimurium survival within macrophages or virulence within mice. A subtracted genomic fragment derived from the ferrichrome operon also hybridized to the intramacrophage cDNA. Nucleotide sequence analysis ofS. typhimurium andS. typhi chromosomal sequences flanking the ferrichrome operon identified a novelS. typhimurium fimbrial operon with a high level of similarity to sequences encodingProteus mirabilis mannose-resistant fimbriae. The novel fimbrial operon was absent from theS. typhi genome. The absence of specific genes may have allowedS. typhi to evolve as a highly invasive, systemic human pathogen.

infection and immunity

Genomic Subtractive Hybridization and Selective Capture of Transcribed Sequences Identify a Novel<i>Salmonella typhimurium</i>Fimbrial Operon and Putative Transcriptional Regulator That Are Absent from the<i>Salmonella typhi</i>Genome

Genomic Subtractive Hybridization and Selective Capture of Transcribed Sequences Identify a NovelSalmonella typhimuriumFimbrial Operon and Putative Transcriptional Regulator That Are Absent from theSalmonella typhiGenome