Oligomeric coiled-coil adhesin YadA is a double-edged sword.
Oligomeric coiled-coil adhesin YadA is a double-edged sword.
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DOI：
10.1371/journal.pone.0015159
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发表时间：
2010-12-08
期刊：
影响因子：
3.7
通讯作者：
Cornelis GR
中科院分区：
文献类型：
--
作者：
Casutt-Meyer S;Renzi F;Schmaler M;Jann NJ;Amstutz M;Cornelis GR
耶尔森氏菌粘附素A （YadA）是食源性致病菌小肠结肠炎耶尔森氏菌和假结核耶尔森氏菌的重要毒力因子。令人惊讶的是，它是鼠疫耶尔森氏菌的假基因。更有趣的是，在小鼠模型中，在鼠疫杆菌EV76中引入功能性yadA基因被证明与毒力下降有关。在这里，我们报道野生型（wt）小肠结肠炎耶氏杆菌E40和缺乏yda的E40在与中性粒细胞接触后诱导中性粒细胞胞外陷阱（NETs）的合成，但只有表达yda的小肠结肠炎耶氏杆菌粘附在NETs上并被杀死。由于结合似乎是杀死的先决条件，我们寻找了与yada结合的底物，并在NETs中检测到了胶原蛋白的存在。表达V98D、N99A突变体YadA的E40细菌与胶原结合能力严重降低，抗杀伤能力更强，表明胶原结合对NETs的敏感性有显著影响。Wt鼠疫耶氏菌EV76对net的杀伤具有抗性，而表达假结核耶氏菌或小肠结肠炎耶氏菌YadA的重组EV76对net的杀伤具有敏感性，这说明了YadA对net依赖性杀伤的敏感性的重要性。如前所述，携带小肠结肠炎耶氏菌YadA的重组EV76对小鼠的毒力也比携带小肠结肠炎耶氏菌YadA的重组EV76弱。此外，携带YadA的EV76对小鼠的毒力低于表达YadAV98D、N99A的EV76。YadA使耶尔森氏菌对NETs敏感的观察结果，解释了为什么进化选择了跳蚤传播的鼠疫杆菌中YadA的失活，并澄清了一个古老的谜团。由于YadA对食源性耶尔森氏菌施加了相同的代价，但却在进化中得到了保存，这一观察结果也说明了某些毒力功能的二重性。
Yersinia adhesin A (YadA) is an essential virulence factor for the food-borne pathogens Yersinia enterocolitica and Yersinia pseudotuberculosis. Suprisingly, it is a pseudogene in Yersinia pestis. Even more intriguing, the introduction of a functional yadA gene in Y. pestis EV76 was shown to correlate with a decrease in virulence in a mouse model. Here, we report that wild type (wt) Y. enterocolitica E40, as well as YadA-deprived E40 induced the synthesis of neutrophil extracellular traps (NETs) upon contact with neutrophils, but only YadA-expressing Y. enterocolitica adhered to NETs and were killed. As binding seemed to be a prerequisite for killing, we searched for YadA-binding substrates and detected the presence of collagen within NETs. E40 bacteria expressing V98D,N99A mutant YadA with a severely reduced ability to bind collagen were found to be more resistant to killing, suggesting that collagen binding contributes significantly to sensitivity to NETs. Wt Y. pestis EV76 were resistant to killing by NETs, while recombinant EV76 expressing YadA from either Y. pseudotuberculosis or Y. enterocolitica were sensitive to killing by NETs, outlining the importance of YadA for susceptibility to NET-dependent killing. Recombinant EV76 endowed with YadA from Y. enterocolitica were also less virulent for the mouse than wt EV76, as shown before. In addition, EV76 carrying wt YadA were less virulent for the mouse than EV76 expressing YadAV98D,N99A. The observation that YadA makes Yersinia sensitive to NETs provides an explanation as for why evolution selected for the inactivation of yadA in the flea-borne Y. pestis and clarifies an old enigma. Since YadA imposes the same cost to the food-borne Yersinia but was nevertheless conserved by evolution, this observation also illustrates the duality of some virulence functions.
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影响因子：
3.2
作者：
CORNELIS, G;SLUITERS, C;MICHIELS, T
通讯作者：
MICHIELS, T
影响因子：
6.6
作者：
Boyd, AP;Grosdent, N;Cornelis, GR
通讯作者：
Cornelis, GR
影响因子：
3.1
作者：
CHINA, B;NGUYEN, BT;CORNELIS, GR
通讯作者：
CORNELIS, GR
DOI：
10.1099/00221287-87-2-285
发表时间：
1975-01-01
期刊：
JOURNAL OF GENERAL MICROBIOLOGY
影响因子：
--
作者：
CORNELIS, G;COLSON, C
通讯作者：
COLSON, C
影响因子：
2.7
作者：
Gupta, AK;Hasler, P;Hahn, S
通讯作者：
Hahn, S