We have sequenced the genome of Shigella flexneri serotype 2a, the most prevalent species and serotype that causes bacillary dysentery or shigellosis in man. The whole genome is composed of a 4 607 203 bp chromosome and a 221 618 bp virulence plasmid, designated pCP301. While the plasmid shows minor divergence from that sequenced in serotype 5a, striking characteristics of the chromosome have been revealed. The S.flexneri chromosome has, astonishingly, 314 IS elements, more than 7-fold over those possessed by its close relatives, the non-pathogenic K12 strain and enterohemorrhagic O157:H7 strain of Escherichia coli. There are 13 translocations and inversions compared with the E.coli sequences, all involve a segment larger than 5 kb, and most are associated with deletions or acquired DNA sequences, of which several are likely to be bacteriophage-transmitted pathogenicity islands. Furthermore, S.flexneri, resembling another human-restricted enteric pathogen, Salmonella typhi, also has hundreds of pseudogenes compared with the E.coli strains. All of these could be subjected to investigations towards novel preventative and treatment strategies against shigellosis.
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We thank Paul Langford, Janine Bosse and Alick Stephens for critical reading of the manuscript, and the following for technical support: Shu Wang, Tianjing Cai, Yingying Xi, Xinyu Tan, Yanrui Jiang, Shitao Zhuang, Xinfeng Zhou, Li Rong, Tao Lu, Wei Liu and Lihong Chen from National Center of Human Genome Research, Beijing, and Shuiyun Lan, Yueqing Zhang and Minjie Chen from Fudan University for their expert technical assistance. This project was supported by the State Key Basic Research Program (grant no. G1999054103) and High Technology Project (grant no. Z19-02-05-01) from the Ministry of Science and Technology of China.