Mathematical modelling reveals properties of TcdC required for it to be a negative regulator of toxin production in Clostridium difficile.

Mathematical modelling reveals properties of TcdC required for it to be a negative regulator of toxin production in Clostridium difficile.
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DOI:
10.1007/s00285-014-0780-0
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发表时间:
2015-03
影响因子:
1.9
通讯作者:
King, John R.
King, John R.
中科院分区:
数学4区
文献类型:
--
作者:
Jabbari, Sara;Cartman, Stephen T.;King, John R.

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目前尚不清楚TcdC蛋白在艰难梭菌致病性中的作用:相互矛盾的报告表明,它要么是毒素产生的负调节因子,要么对毒力完全没有影响。我们利用了一种理论方法,将已知的围绕艰难梭菌毒素产生的蛋白质网络转化为数学模型。从那里可以研究一系列可能的相互作用(使用数值和渐近分析),确定TcdC的特性,使其成为毒素抑制剂的现实候选者。我们的研究结果表明,如果TcdC真的是一种毒素产生的抑制剂,那么TcdC的产生应该至少和TcdR蛋白的产生一样快,并且TcdC应该在细胞的整个生长过程中都保持在细胞中。这些都是实验可检验的假设,同样适用于毒素产生抑制的替代候选物。
The role of the protein TcdC in pathogenicity of the bacterium Clostridium difficile is currently unclear: conflicting reports suggest it is either a negative regulator of toxin production or, on the other hand, has no effect on virulence at all. We exploit a theoretical approach by taking what is known about the network of proteins surrounding toxin production by C. difficile and translating this into a mathematical model. From there it is possible to investigate a range of possible interactions (using numerical and asymptotic analyses), identifying properties of TcdC which would make it a realistic candidate as a toxin inhibitor. Our findings imply that if TcdC is really an inhibitor of toxin production then TcdC production should be at least as fast as that of the protein TcdR and TcdC should remain in the cells throughout growth. These are experimentally-testable hypotheses and are equally applicable to alternative candidates for toxin production inhibition.
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