Genome sequence of adherent-invasive Escherichia coli and comparative genomic analysis with other E. coli pathotypes.

Genome sequence of adherent-invasive Escherichia coli and comparative genomic analysis with other E. coli pathotypes.
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DOI:
10.1186/1471-2164-11-667
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发表时间:
2010-11-25
期刊:
影响因子:
4.4
通讯作者:
Coombes BK
Coombes BK
中科院分区:
生物学2区
文献类型:
--
作者:
Nash JH;Villegas A;Kropinski AM;Aguilar-Valenzuela R;Konczy P;Mascarenhas M;Ziebell K;Torres AG;Karmali MA;Coombes BK

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粘附性和侵袭性大肠杆菌(AIEC)通常在克罗恩病(CD)患者的回肠病变中发现,其中它们粘附于肠上皮细胞并侵入上皮细胞和巨噬细胞并在其中存活,从而获得进入通常受限的宿主生态位的途径。定植导致肠道中强烈的炎症反应,表明AIEC可能在CD免疫病理学中发挥作用。尽管进行了广泛的调查,占AIEC表型的遗传决定因素仍然不清楚。为了解决这个问题,我们提出了完整的基因组序列的AIEC,揭示了这种疾病相关的E。大肠杆菌致病型。我们测定了E. coli NRG 857c(O83:H1),一株从克罗恩病患者回肠分离的AIEC临床分离株。我们的序列数据证实了AIEC和肠外致病性E.大肠杆菌引起尿路感染和新生儿脑膜炎。将NRG857c AIEC基因组与其它致病性大肠杆菌和大肠杆菌的基因组进行了比较。大肠杆菌允许鉴定AIEC致病型的独特遗传特征,包括41个基因组岛,以及仅在表现出粘附和侵袭表型的菌株中发现的独特基因。到目前为止,与AIEC相关的毒性样特征仅在表型上可检测到。AIEC基因组序列数据将有助于识别与入侵和细胞内生长有关的遗传决定因素,并使健康和疾病期间AIEC基因表达的功能基因组研究成为可能。
Adherent and invasive Escherichia coli (AIEC) are commonly found in ileal lesions of Crohn's Disease (CD) patients, where they adhere to intestinal epithelial cells and invade into and survive in epithelial cells and macrophages, thereby gaining access to a typically restricted host niche. Colonization leads to strong inflammatory responses in the gut suggesting that AIEC could play a role in CD immunopathology. Despite extensive investigation, the genetic determinants accounting for the AIEC phenotype remain poorly defined. To address this, we present the complete genome sequence of an AIEC, revealing the genetic blueprint for this disease-associated E. coli pathotype. We sequenced the complete genome of E. coli NRG857c (O83:H1), a clinical isolate of AIEC from the ileum of a Crohn's Disease patient. Our sequence data confirmed a phylogenetic linkage between AIEC and extraintestinal pathogenic E. coli causing urinary tract infections and neonatal meningitis. The comparison of the NRG857c AIEC genome with other pathogenic and commensal E. coli allowed for the identification of unique genetic features of the AIEC pathotype, including 41 genomic islands, and unique genes that are found only in strains exhibiting the adherent and invasive phenotype. Up to now, the virulence-like features associated with AIEC are detectable only phenotypically. AIEC genome sequence data will facilitate the identification of genetic determinants implicated in invasion and intracellular growth, as well as enable functional genomic studies of AIEC gene expression during health and disease.
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