What's a SNP between friends: The influence of single nucleotide polymorphisms on virulence and phenotypes of Clostridium difficile strain 630 and derivatives.
What's a SNP between friends: The influence of single nucleotide polymorphisms on virulence and phenotypes of Clostridium difficile strain 630 and derivatives.
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DOI：
10.1080/21505594.2016.1237333
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发表时间：
2017-08-18
期刊：
影响因子：
5.2
通讯作者：
Minton NP
中科院分区：
文献类型：
--
作者：
Collery MM;Kuehne SA;McBride SM;Kelly ML;Monot M;Cockayne A;Dupuy B;Minton NP
艰难梭菌是世界范围内抗生素诱导的腹泻的主要原因，造成显著的年度死亡率，并对医疗保健系统造成相当大的经济负担。两个主要的C。艰难梭菌的毒力因子是毒素A和B。菌株630的2个独立分离的红霉素敏感衍生物（630 E和630Δ E）的同基因毒素B突变体先前显示出实质上不同的表型。与630相比，菌株630 E及其子代生长较慢，最终细胞密度较低，孢子形成能力降低，毒素水平较低，在仓鼠感染模型中毒性较低。通过相同的测量，应变630Δ ε及其导数更接近地反映630的行为。基因组测序结果显示，630Δ E630株具有7个独特的单核苷酸多态性（SNPs），而630 E有9个SNPs，另外2株没有发现DNA倒位。相对大量的突变意味着不可能鉴定出导致630 E特性改变的那些突变，尽管通过等位基因交换和所有3种菌株的比较RNAseq分析将3种突变恢复为野生型。后一种分析揭示了3种菌株之间基因表达的巨大差异，部分解释了为什么没有单一SNP可以恢复表型差异。我们的研究结果表明，在基于遗传的研究中，菌株630Δ ε应优于630 E作为630的替代物。他们还强调了有效菌株管理的重要性，以及尽可能对主种子库进行基因组重新测序的必要性。
Clostridium difficile is a major cause of antibiotic induced diarrhea worldwide, responsible for significant annual mortalities and represents a considerable economic burden on healthcare systems. The two main C. difficile virulence factors are toxins A and B. Isogenic toxin B mutants of 2 independently isolated erythromycin-sensitive derivatives (630E and 630Δerm) of strain 630 were previously shown to exhibit substantively different phenotypes. Compared to 630, strain 630E and its progeny grow slower, achieve lower final cell densities, exhibit a reduced capacity for spore-formation, produce lower levels of toxin and are less virulent in the hamster infection model. By the same measures, strain 630Δerm and its derivatives more closely mirror the behavior of 630. Genome sequencing revealed that 630Δerm had acquired 7 unique Single Nucleotide Polymorphisms (SNPs) compared to 630 and 630E, while 630E had 9 SNPs and a DNA inversion not found in the other 2 strains. The relatively large number of mutations meant that the identification of those responsible for the altered properties of 630E was not possible, despite the restoration of 3 mutations to wildtype by allelic exchange and comparative RNAseq analysis of all 3 strains. The latter analysis revealed large differences in gene expression between the 3 strains, explaining in part why no single SNP could restore the phenotypic differences. Our findings suggest that strain 630Δerm should be favored over 630E as a surrogate for 630 in genetic-based studies. They also underline the importance of effective strain curation and the need to genome re-sequence master seed banks wherever possible.
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影响因子：
48
作者：
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通讯作者：
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影响因子：
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作者：
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