痢疾杆菌全基因组序列及基因组岛的分析

Complete Genome Sequence of Shigella flexneri 2a 301 Strain and Analysis of “ Shigella-islands

福氏 2a志贺菌 (Shigellaflexneriserotype 2a)是引起人类细菌性痢疾的主要病原体。本文在国际上首次完成了福氏 2a志贺菌 30 1株 (Sf30 1) (我国细菌性痢疾的优势流行株 )的全基因组核苷酸序列测定和初步分析。该基因组包括一条由 4 6 0 72 0 3个碱基对 (bp)组成的环状染色体和一个含 2 2 16 18bp的侵袭性大质粒pCP30 1以及另外两个小质粒。通过将Sf30 1的染色体序列与其亲源关系相近的非致病性大肠杆菌K - 12菌株MG16 5 5进行比较基因组学研究 ,发现Sf30 1的染色体上有 5 72Kb特异性序列 ,并形成了 32 0个长度大于 5 0bp的“痢疾岛” (Shigella island ,SIs) ,其中大于 1Kb的共计 131个。这些岛共包含 5 19个开放读码框架 (OpenReadingFrames,ORFs) ,多数SIs的一侧或两侧均伴有插入序列元件、转座子或者tRNAs。G +C含量及密码子使用频率等分析显示出部分SIs的外源性。通过结构及ORF编码产物功能的分析 ,鉴别出 9个可能与痢疾杆菌致病性有关的“毒力岛” ,其中

Shigella flexneri serotype 2a are the most prevalent species and serotype that cause bacillary dysentery or shigellosis in man. This paper presents the complete genome sequence of a Shigella flexneri 2a strain which isolated from the Beijing outbreak, and the primary analysis of “ Shigella genomic islands (SIs)' that means Shigella flexneri 2a 301 strain specific genome fragments. The whole genome is composed of a 4,607,203 bp chromosome and a 221,618 bp virulence plasmid, designated pCP301. The chromosome shares a conserved ‘backbone' sequence about 4 03 Mb with those of a benign laboratory strain E.coli K12 (MG1655) which is essentially collinear. Sf301 has 572 Kb specific sequence which form into 320 SIs with sizes greater than 50 bp and encoding in total 519 Shigella specific Open Reading Frames (ORFs). Among these SIs, there are 131 islands with sizes greater than 1 Kb with repeated sequences of transposable elements, transposons or tRNAs flanking on one or both sides. The average G+C content of the SIs is 48 25%, significantly lower than that of the conserved backbone. Frequency of codons such as ACA, AAT, GCG, CTG, etc., on SIs are quite distinct from that on backbone sequences. All above observations together suggest that many of the SIs are foreign origin. Among them, the authors identified 7 putative SIs with typical structure of pathogenicity islands (PAI) and 2 SIs harbor some ORFs related to biosynthesis of lipopolysaccharide (LPS) have implications in virulence, in addition to the previously identified PAIs, SHE and SHI\|2. The other SIs are mostly a mosaic of genes of known function and ORFs encoding polypeptides sharing none or low homology with known proteins from one or more bacterial species. All of these could be subjected to investigations towards novel preventive and treatment strategies against shigellosis. [