Host Restriction

The 1454 different serotypes that can currently be distinguished within S. enterica subspecies I [1] contain a few specialists that appear to be better adapted to their respective host species than other members of the genus Salmonella. These "specialists" commonly cause a systemic infection in their preferred host species but are isolated infrequently from other host species. These features are perhaps best exemplified by S. enterica serotype Typhi, the cause of typhoid fever, and S. enterica serotype Paratyphi A, a cause of paratyphoid fever in humans. Both serotypes persist in the human population by person-to-person transmission through contaminated food or water but are rarely isolated from nonhuman vertebrates. Furthermore, S. enterica serotypes Typhi and Paratyphi A do not cause disease in nonprimate vertebrates or even in lower primate species. Although there has been substantial interest in identifying the molecular basis for this host restriction, the bacterial genes responsible have long eluded identification. Recent genome sequence analysis shows that the genomes of the generalist S. enterica serotype Typhimur-ium strain LT2 and the two sequenced S. enterica serotype Typhi isolates (CT18 and TY2) have similar sizes (4857kbp, 4809kbp, and 4792 kbp respectively), while the S. enterica serotype Paratyphi A genome is somewhat smaller (4585 kbp) [4, 42-44]. Comparison of these genomes and microarray analysis have allowed direct comparison between more generalist and more specialist genomes, and have provided first insights into the genetic changes accompanying the evolution of host-restricted serotypes [4, 5, 7, 42-44, 46, 61]. The genetic differences between the host generalist and the host specialist can be classified into four categories: (1) genes present in the generalist genome that are absent from the specialist genome, (2) pseudo-genes, (3) genes present in the specialist genome that are absent from the generalist genome, and (4) rearrangements of gene order in the genome itself.

Genomic comparison of 18 different Salmonella serotypes using a S. enterica serotype Typhimurium strain LT2-based microarray revealed a cluster of genes belonging to the first category: those absent from strictly human-adapted sero-types (Typhi and Paratyphi A) but present in other serotypes of S. enterica subspecies I [7]. While 99.5% of genes present on the S. enterica serotype Typhimurium microarray had homologues in the genomes of other S. enterica serotype Typhi-murium isolates (SARA1, SARA6), only between 89% and 94% had homologues in the genomes of S. enterica serotypes Typhi and Paratyphi A isolates. The majority of the genes absent from S. enterica serotypes Typhi and Paratyphi A isolates were also absent from genomes of other generalist serotypes. However, cluster analysis identified a group of 53 genes whose absence was a shared genetic feature of genomes of strictly human-adapted S. enterica subspecies I serotypes. The

Table6.1 Genome degradation affecting fimbria! and nonfimbrial adherence determinants in typhoidal Salmonella serotypes compared to S. enterica serotype Typhimurium.

Genetic Determinant (pseudogene) present in the genome ofS. enterica serotype determinant -

Typhimurium Paratyphi A Typhi strain CT18 Typhi strain Ty2

strain LT2 strain SARB42

shdA

+

+ (shdA)

+ (shdA)

+ (shdA)

misL

+

+

+ (misL)

+ (misL)

sivH

+

+ (sivH)

+ (sivH)

+ (sivH)

ratB

+

+ (ratB)

+ (ratB)

+ (ratB)

csg (agf)

+

+ (csgF)

+

+

fim

+

+

+ (Jiml)

+

tcf

0 0

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