Identification and characterization of Helicobacter pylori genes essential for gastric colonization.
Identification and characterization of Helicobacter pylori genes essential for gastric colonization.
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DOI：
10.1084/jem.20021531
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发表时间：
2003-04-07
期刊：
影响因子：
--
通讯作者：
Haas R
中科院分区：
文献类型：
--
作者：
Kavermann H;Burns BP;Angermuller K;Odenbreit S;Fischer W;Melchers K;Haas R
幽门螺杆菌引起最常见的慢性细菌感染之一，是严重胃病的主要原因。为了阐明细菌在胃内定植和致病过程中所必需的因素，我们采用了特征标记诱变（STM）技术对H。幽门。以长爪沙鼠（Meriones unguiculatus）为模型系统，筛选了960个STM突变体。结果是47 H。幽门螺杆菌基因，分配到9个不同的功能类别，代表了一套生物学功能绝对必要的胃定植，验证和量化的许多突变体的竞争实验。对已知的定植因子如尿素酶和运动功能的鉴定证实了该方法的有效性，但也发现了一些新的和假设的基因，有趣的是，一种分泌型胶原酶，由hp0169编码，可以被鉴定和功能验证为H.幽门胃定植。此外，comB4编码一个推定的ATP酶，是H.幽门螺杆菌被认为是绝对必要的殖民，但自然的转化能力显然不是必要的功能。因此，这第一个系统的STM应用程序识别了一组以前未知的H。幽门螺杆菌定植因素，并可能有助于加强对胃螺杆菌感染的新疗法的发展。
Helicobacter pylori causes one of the most common, chronic bacterial infections and is a primary cause of severe gastric disorders. To unravel the bacterial factors necessary for the process of gastric colonization and pathogenesis, signature tagged mutagenesis (STM) was adapted to H. pylori. The Mongolian gerbil (Meriones unguiculatus) was used as model system to screen a set of 960 STM mutants. This resulted in 47 H. pylori genes, assigned to 9 different functional categories, representing a set of biological functions absolutely essential for gastric colonization, as verified and quantified for many mutants by competition experiments. Identification of previously known colonization factors, such as the urease and motility functions validated this method, but also novel and several hypothetical genes were found. Interestingly, a secreted collagenase, encoded by hp0169, could be identified and functionally verified as a new essential virulence factor for H. pylori stomach colonization. Furthermore, comB4, encoding a putative ATPase being part of a DNA transformation-associated type IV transport system of H. pylori was found to be absolutely essential for colonization, but natural transformation competence was apparently not the essential function. Thus, this first systematic STM application identified a set of previously unknown H. pylori colonization factors and may help to potentiate the development of novel therapies against gastric Helicobacter infections.
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DOI：
10.1073/pnas.012602299
发表时间：
2002-01-22
影响因子：
11.1
作者：
Akerley, BJ;Rubin, EJ;Mekalanos, JJ
通讯作者：
Mekalanos, JJ
DOI：
10.1073/pnas.95.4.1818
发表时间：
1998-02-17
影响因子：
11.1
作者：
Graf, J;Ruby, EG
通讯作者：
Ruby, EG
影响因子：
15.9
作者：
Blaser, MJ;Berg, DE
通讯作者：
Berg, DE
影响因子：
64.8
作者：
Alm, RA;Ling, LSL;Trost, TJ
通讯作者：
Trost, TJ
DOI：
10.1073/pnas.122244899
发表时间：
2002-06-11
影响因子：
11.1
作者：
Guo, BP;Mekalanos, JJ
通讯作者：
Mekalanos, JJ