Significance and context
Salmonella species are Gram negative bacteria first discovered by the American veterinary scientist D.E. Salmon at the end of the 19th century, and are the cause of salmonellosis in humans. The salmonellae are taxonomically subdivided into Salmonella enterica and Salmonella bongori. To S. enterica belong over 2,000 serovars that are grouped into seven subspecies. It has recently been shown that a common ancestor acquired the mechanism of flagellar antigen shifting, which is considered to be an adaptation to life in warm-blooded hosts. Using DNA microarray technology, Porwollik et al. compared the genetic content of the entirely sequenced genome of the agent of mouse typhoid, S. enterica serovar typhimurium LT2, and that of several other salmonellae, revealing genes that may be responsible for LT2-related phenotypes in the salmonellae that infect humans.
A microarray of PCR-amplified whole open reading frames (ORFs) was constructed, consisting of more than 97% of the 4,596 coding sequences in the S. enterica sv. typhimurium LT2 genome. The genetic content of S. enterica sv. typhimurium LT2 was compared with that of other S. enterica strains and S. bongori. Porwollik et al. showed that 1,424 LT2 genes were absent or too divergent to be detected in at least one of the other Salmonella genomes tested. On comparison of the LT2 genomic content with that of other enteric bacteria, for example Escherichia coli K12 and O157:H7, Klebsiella pneumoniae MGH78578, and Yersinia pestis CO92, whose genomes have been sequenced, 935 LT2-specific genes were identified. Of those, 56 were present in all 22 Salmonella strains used in this study, and these included, for instance, genes encoding a DNA helicase, a tetrathionate reductase enzyme complex, anaerobic sulfide reductase, putative inner and outer membrane proteins, and other genes whose functions still need to be determined. Homologs of the five Salmonella pathogenesis islands (SPIs) vary among the different Salmonella strains. For example, most of the genes of SPI1 are present in all Salmonella strains tested but most of the genes of SPI2 are absent from S. bongori. Only S. enterica subspecies I has a full set of all SPIs present in S. enterica sv. typhimurium LT2. On the basis of microarray analyses, a bifurcating taxonomic tree was constructed that suggests how S. enterica sv. typhimurium LT2 has evolved and which genes have been acquired during evolution. It was estimated that 513 genes were gained since the formation of the genus Salmonella. These include, for instance, genes encoding a second type-III secretion system, certain fimbrial genes, genes encoding a phosphoglycerate transport system, and the rfb cluster involved in the synthesis of lipopolysaccharides. Finally, when S. enterica sv. typhimurium LT2 evolved, it acquired another fimbrial operon, a number of prophages, and a large set of genes of unknown function.
Porwollik et al. compared the genetic content of S. enterica sv. typhimurium LT2, responsible for most Salmonella infections in humans, with that of a set of other Salmonella strains. They thereby determined a set of genes that are predicted to have been acquired during Salmonella evolution. Those genes may be important during infection of humans and/or survival in warm-blooded hosts. Future work should include a biochemical characterization of those genes accompanied by a study of their role during Salmonella infection. The fact that the function of a large number of those genes is currently unknown suggests that many steps in the mechanism of Salmonella infection of humans still need to be deciphered. This research should indicate candidate target proteins that will be useful in developing new therapeutic strategies.