The NEAT Domain-Containing Proteins of Clostridium perfringens Bind Heme
The NEAT Domain-Containing Proteins of Clostridium perfringens Bind Heme
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DOI：
10.1371/journal.pone.0162981
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发表时间：
2016-09-16
期刊：
影响因子：
3.7
通讯作者：
Awad, Milena M.
中科院分区：
文献类型：
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作者：
Choo, Jocelyn M.;Cheung, Jackie K.;Awad, Milena M.
在感染期间，致病菌从宿主体内清除铁元素的能力对其生长和存活至关重要。我们对产气荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜荚膜。通过对产气荚膜梭菌菌株13基因组序列的分析，发现了一个由铁调控的表面基因区编码的血红素获取系统，我们将其命名为Cht （Clostridium perfringens血红素运输）位点。该基因座由共转录的8个基因组成，其中包括编码含NEAT结构域蛋白（ChtD和ChtE）的基因和一个假定的分选酶（Srt）。ChtD， ChtE和Srt蛋白在铁限制条件下生长的JIR325细胞中表达，并定位于细胞包膜。此外，还发现了与血红素结合的NEAT蛋白ChtD和ChtE。构建了chtDE和srt突变体，但这些突变体在血红蛋白和氯化铁利用方面没有缺陷。然而，当在小鼠肌坏死模型中进行测试时，它们的毒力被减弱，尽管毒力表型不能通过互补恢复，并且在这些菌株中发现了继发性突变，这在此类系统中很常见。总之，本研究为这种威胁生命的病原体血红素运输途径中发生的功能冗余提供了证据。
The ability of a pathogenic bacterium to scavenge iron from its host is important for its growth and survival during an infection. Our studies on C. perfringens gas gangrene strain JIR325, a derivative of strain 13, showed that it is capable of utilizing both human hemoglobin and ferric chloride, but not human holo-transferrin, as an iron source for in vitro growth. Analysis of the C. perfringens strain 13 genome sequence identified a putative heme acquisition system encoded by an iron-regulated surface gene region that we have named the Cht (Clostridium perfringens heme transport) locus. This locus comprises eight genes that are co-transcribed and includes genes that encode NEAT domain-containing proteins (ChtD and ChtE) and a putative sortase (Srt). The ChtD, ChtE and Srt proteins were shown to be expressed in JIR325 cells grown under iron-limited conditions and were localized to the cell envelope. Moreover, the NEAT proteins, ChtD and ChtE, were found to bind heme. Both chtDE and srt mutants were constructed, but these mutants were not defective in hemoglobin or ferric chloride utilization. They were, however, attenuated for virulence when tested in a mouse myonecrosis model, although the virulence phenotype could not be restored via complementation and, as is common with such systems, secondary mutations were identified in these strains. In summary, this study provides evidence for the functional redundancies that occur in the heme transport pathways of this life threatening pathogen.