Neisseria meningitidis rifampicin resistant strains: analysis of protein differentially expressed
Neisseria meningitidis rifampicin resistant strains: analysis of protein differentially expressed
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DOI：
10.1186/1471-2180-10-246
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发表时间：
2010-09-24
期刊：
影响因子：
4.2
通讯作者：
Stefanelli, Paola
中科院分区：
文献类型：
--
作者：
Neri, Arianna;Mignogna, Giuseppina;Stefanelli, Paola
背景：脑膜炎奈瑟菌中有几种突变被认为是引起利福平耐药的原因。然而，为什么这些菌株如此罕见的有趣问题仍然悬而未决。本研究的目的是利用双向电泳结合质谱技术研究2株利福平耐药脑膜炎球菌和1株敏感脑膜炎球菌的蛋白质含量，并鉴定特异性蛋白质的差异表达。在我们的实验条件下，能够分辨等电点在4和7之间的可溶性蛋白质，与易感菌株相比，已经发现23种蛋白质在两种抗性菌株中差异表达。其中一些参与主要代谢途径，表现出增加的表达，主要是在丙酮酸的催化和三羧酸循环。还观察到属于基因调控和参与多肽折叠的蛋白质的表达降低。2-DE分析表明，在两个耐药菌株中，显示其等电点的偏移的四个蛋白质的存在下，证实了在序列分析中的氨基酸变化的存在下，不存在于sensitive.Conclusions：差异表达的蛋白质的分析表明，一个复杂的一系列事件发生在N。脑膜炎球菌利福平耐药菌株和结果，这里报道可以被认为是一个起点，在了解他们的入侵能力下降。事实上，他们支持这样的假设，即存在一种以上的差异表达蛋白，在脑膜炎球菌的代谢中起作用，影响其感染和在人群中传播的能力。不同的报告已经描述和讨论了耐药病原体如何表现出较高的生存生物成本，这也可以解释为什么对于某些病原体，考虑到特定药物的广泛使用，耐药生物体的比率相对较低。这似乎是利福平耐药脑膜炎球菌的情况。
Background: Several mutations have been described as responsible for rifampicin resistance in Neisseria meningitidis. However, the intriguing question on why these strains are so rare remains open. The aim of this study was to investigate the protein content and to identify differential expression in specific proteins in two rifampicin resistant and one susceptible meningococci using two-dimensional electrophoresis (2-DE) combined with mass spectrometry.Results: In our experimental conditions, able to resolve soluble proteins with an isoelectric point between 4 and 7, twenty-three proteins have been found differentially expressed in the two resistant strains compared to the susceptible. Some of them, involved in the main metabolic pathways, showed an increased expression, mainly in the catabolism of pyruvate and in the tricarboxylic acid cycle. A decreased expression of proteins belonging to gene regulation and to those involved in the folding of polypeptides has also been observed. 2-DE analysis showed the presence of four proteins displaying a shift in their isoelectric point in both resistant strains, confirmed by the presence of amino acid changes in the sequence analysis, absent in the susceptible.Conclusions: The analysis of differentially expressed proteins suggests that an intricate series of events occurs in N. meningitidis rifampicin resistant strains and the results here reported may be considered a starting point in understanding their decreased invasion capacity. In fact, they support the hypothesis that the presence of more than one protein differentially expressed, having a role in the metabolism of the meningococcus, influences its ability to infect and to spread in the population. Different reports have described and discussed how a drug resistant pathogen shows a high biological cost for survival and that may also explain why, for some pathogens, the rate of resistant organisms is relatively low considering the widespread use of a particular drug. This seems the case of rifampicin resistant meningococci.