Comparative Genomics of Shigella

In contrast to E. coli, Shigella flexneri is pathogenic only for humans. S.flexneri can invade the colon epithelium and cause intense acute inflammatory response. Its ability to enter the host cell cytosol, where it can replicate and spread into neighboring cells, is unusual among enterobacteria. Mainly responsible for the invasive character is a large virulence plasmid that contains the genes required for invasion. Additionally, chromosomal genes located within pathogenicity islands contribute directly to the pathogenic process and to survival during infection [12, 13]. Consequently, genome comparison of S.flexneri and the phylogenetically indistinguishable E. coli should enable identification of the basis of the specific clinical manifestation of S. flexneri infection. The genomes of two S. flexneri serotype 2a strains, 2457Tand 301, have been completely sequenced and some of their characteristics are compiled in Table 5.1. Full genome sequence determination of one S. dysenteriae and one S. boydii strain is in progress (http://www.sanger.ac.uk/Pro-jects/Microbes/) (see also Table 5.2). The S.flexneri chromosome exhibits the conserved backbone and flexible island mosaic structure typical of E. coli/Shigella. The genome sequences are very similar, comprising a common colinear chromosomal backbone of 3.9 million base pairs (Mbp) which is also shared with E.coli K-12 strain MG1655 and the O157:H7 strain EDL933. Nevertheless, more than 1400 single nucleotide exchanges have been observed which are scattered all over the S.flexneri genome. Strain 301 carries an unusual set of three spacer tRNAs in the rrnH operon [14, 15]. The strain 2457T genome lacks 357 E. coli genes and contains a large fraction of accessory and (formerly) mobile genetic elements, i.e., 284 intact or nonfunctional insertion sequence (IS) elements that mediated several genomic rearrangements, as well as cryptic prophages. The number of IS-related DNA stretches (n=314) is even higher in the genome of strain 301 [14, 15], thus also increasing the genome size of strain 301 relative to that of strain 2457T.

Accordingly, S.flexneri genomes carry more IS elements than those of any other enteric bacteria. Colinearity of the chromosomal backbone in both genomes is disturbed due to apparently IS-element-mediated chromosomal rearrangements relative to each other and to E. coli K-12. There are at least 15 larger rearrangements between the two Shigella genomes, and nearly all inversions are bordered by insertion sequences. Large rearrangements exist, e.g., around the origin of replication. Around the replication terminus a large inversion occurred in both Shigella strains, followed by reinversion of most of the rearranged DNA region, so that two smaller stretches of inverted sequences indicate the beginning and the end points of the initial event. This implies that the major driving force behind these rearrangements within the S.flexneri genome is recombination between related IS elements.

Tab. 5.1 Characteristics of publicly available complete E. coli and S.flexneri genome sequences.

Strain

Pathotype

Size (bp)

ORFs

No. ofISs or IS-like elements

No. of prophages or prophage-like elements

Plasmids

Reference

S.flexneri 2457T

2a

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