Comparative genomics and proteomics of Helicobacter mustelae, an ulcerogenic and carcinogenic gastric pathogen

Comparative genomics and proteomics of Helicobacter mustelae, an ulcerogenic and carcinogenic gastric pathogen
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DOI:
10.1186/1471-2164-11-164
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发表时间:
2010-03-10
期刊:
影响因子:
4.4
通讯作者:
Bentley, Stephen D.
Bentley, Stephen D.
中科院分区:
生物学2区
文献类型:
--
作者:
O'Toole, Paul W.;Snelling, William J.;Bentley, Stephen D.

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背景:鼬螺杆菌可引起雪貂和其他鼬科动物的胃炎、溃疡和胃癌。H. Mustelae是除H.幽门螺旋杆菌,在其自然宿主中引起胃溃疡和癌症。提高对H. mustelae发病机制,以及一般的螺旋杆菌的溃疡和致癌潜力,我们测序了H。结果:在白鼬基因组中,共鉴定出425个在被膜和胞浆蛋白质组中表达的蛋白质。鼬基因组缺乏主要H. pylori毒力因子包括CagA、VacA、BabA、SabA和OipA。然而,它编码10个自转运蛋白表面蛋白,其中7个在表达的蛋白质组中检测到,除了HSR蛋白,是未知的功能。在H. mustelae的霍夫蛋白,其中一些与H.幽门。虽然同源物的推定毒力决定因素的H。pylori(NapA,plasminogen adhesin,collagenase)和空肠弯曲杆菌(CiaB,Peb 4a)。除了白鼬基因组外,它还包括毒力相关基因的独特互补物,包括血凝素/溶血素蛋白和用于在其脂多糖上产生血型A/B的糖基转移酶。胞质蛋白质组中最高表达的264个蛋白质包括许多来自H. pylori中,但H.鼬是独特的。在27个被证明是H. pylori定植的沙鼠中,除三个外,所有的都有H.结论:对致溃疡性家鼠H. mustelae的基因组序列和表达蛋白质组的测定为H. pylori,以研究哺乳动物中细菌性胃癌的发生,并提出cag减去H. pylori菌株可能导致溃疡和癌症。基因组序列以登录号FN 555004保藏在EMBL/GenBank/DDBJ中。
Background: Helicobacter mustelae causes gastritis, ulcers and gastric cancer in ferrets and other mustelids. H. mustelae remains the only helicobacter other than H. pylori that causes gastric ulceration and cancer in its natural host. To improve understanding of H. mustelae pathogenesis, and the ulcerogenic and carcinogenic potential of helicobacters in general, we sequenced the H. mustelae genome, and identified 425 expressed proteins in the envelope and cytosolic proteome.Results: The H. mustelae genome lacks orthologs of major H. pylori virulence factors including CagA, VacA, BabA, SabA and OipA. However, it encodes ten autotransporter surface proteins, seven of which were detected in the expressed proteome, and which, except for the Hsr protein, are of unknown function. There are 26 putative outer membrane proteins in H. mustelae, some of which are most similar to the Hof proteins of H. pylori. Although homologs of putative virulence determinants of H. pylori (NapA, plasminogen adhesin, collagenase) and Campylobacter jejuni (CiaB, Peb4a) are present in the H. mustelae genome, it also includes a distinct complement of virulence-related genes including a haemagglutinin/haemolysin protein, and a glycosyl transferase for producing blood group A/B on its lipopolysaccharide. The most highly expressed 264 proteins in the cytosolic proteome included many corresponding proteins from H. pylori, but the rank profile in H. mustelae was distinctive. Of 27 genes shown to be essential for H. pylori colonization of the gerbil, all but three had orthologs in H. mustelae, identifying a shared set of core proteins for gastric persistence.Conclusions: The determination of the genome sequence and expressed proteome of the ulcerogenic species H mustelae provides a comparative model for H. pylori to investigate bacterial gastric carcinogenesis in mammals, and to suggest ways whereby cag minus H. pylori strains might cause ulceration and cancer. The genome sequence was deposited in EMBL/GenBank/DDBJ under accession number FN555004.