Complete genome sequence of Shigella flexneri 5b and comparison with Shigella flexneri 2a

Abstract

Background: Shigella bacteria cause dysentery, which remains a significant threat to public health. Shigella flexneri is the most common species in both developing and developed countries. Five Shigella genomes have been sequenced, revealing dynamic and diverse features. To investigate the intra-species diversity of S. flexneri genomes further, we have sequenced the complete genome of S. flexneri 5b strain 8401 (abbreviated Sf8401) and compared it with S. flexneri 2a (Sf301).

Results: The Sf8401 chromosome is 4.5-Mb in size, a little smaller than that of Sf301, mainly because the former lacks the SHI-1 pathogenicity island (PAI). Compared with Sf301, there are 6 inversions and one translocation in Sf8401, which are probably mediated by insertion sequences (IS). There are clear differences in the known PAIs between these two genomes. The bacteriophage SfV segment remaining in SHI-O of Sf8401 is clearly larger than the remnants of bacteriophage SfII in Sf301. SHI-1 is absent from Sf8401 but a specific related protein is found next to the pheV locus. SHI-2 is involved in one intra-replichore inversion near the origin of replication, which may change the expression of iut/iuc genes. Moreover, genes related to the glycine-betaine biosynthesis pathway are present only in Sf8401 among the known Shigella genomes.

Conclusion: Our data show that the two S. flexneri genomes are very similar, which suggests a high level of structural and functional conservation between the two serotypes. The differences reflect different selection pressures during evolution. The ancestor of S. flexneri probably acquired SHI-1 and SHI-2 before SHI-O was integrated and the serotypes diverged. SHI-1 was subsequently deleted from the S. flexneri 5b genome by recombination, but stabilized in the S. flexneri 2a genome. These events may have contributed to the differences in pathogenicity and epidemicity between the two serotypes of S. flexneri.

Figure 1

Global comparison of Sf8401 chromosome with Sf301. Each marker length denotes 300 kb for chromosome comparisons. Color code denotes maximal length of the paired segments: red, >10 kb; blue, 5~10 kb; cyan, 1~5 kb. The inversion is abbreviated to IV.

Figure 2

Localized comparison of (a) SHI-O, (b) SHI-1, (c) SHI-2. Arrows indicate predicted ORFs in both strands. The direction of each arrow predicts the direction of transcription. Color code denotes maximal length of the paired segments: red, >10 kb; blue, 5~10 kb cyan; 1~5 kb. (a) The dark green block refers to a large region of bacteriophage SfV in the Sf8401 genome. (b) The yellow block refers to the 22 bp partial repeat sequence of pheV. Black indicates the 12 kb sequence downstream of SHI-1 in Sf301, which does not exist in Sf8401. The asterisk denotes a pseudogene. (c) The replication origin, ori, is indicated by a vertical arrow in each genome. The green block refers to the region that is colinear with the Sf301 genome.