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The bias of experimental design, including strain background, in the determination of critical Streptococcus suis serotype 2 virulence factors

机译:确定猪链球菌2型血清关键毒力因子时,包括菌株背景在内的实验设计的偏倚

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摘要

Streptococcus suis serotype 2 is an important porcine bacterial pathogen and emerging zoonotic agent mainly responsible for sudden death, septic shock, and meningitis. However, serotype 2 strains are genotypically and phenotypically heterogeneous. Though a multitude of virulence factors have been described for S. suis serotype 2, the lack of a clear definition regarding which ones are truly “critical” has created inconsistencies that have only recently been highlighted. Herein, the involvement of two factors previously described as being critical for S. suis serotype 2 virulence, whether the dipeptidyl peptidase IV and autolysin, were evaluated with regards to different ascribed functions using prototype strains belonging to important sequence types. Results demonstrate a lack of reproducibility with previously published data. In fact, the role of the dipeptidyl peptidase IV and autolysin as critical virulence factors could not be confirmed. Though certain in vitro functions may be ascribed to these factors, their roles are not unique for S. suis, probably due to compensation by other factors. As such, variations and discrepancies in experimental design, including in vitro assays, cell lines, and animal models, are an important source of differences between results. Moreover, the use of different sequence types in this study demonstrates that the role attributed to a virulence factor may vary according to the S. suis serotype 2 strain background. Consequently, it is necessary to establish standard experimental designs according to the experiment and purpose in order to facilitate comparison between laboratories. Alongside, studies should include strains of diverse origins in order to prevent erroneous and biased conclusions that could affect future studies.
机译:猪链球菌血清型2是重要的猪细菌病原体和新兴的人畜共患病因子,主要负责猝死,败血性休克和脑膜炎。但是,血清型2菌株在基因型和表型上是异质的。尽管已经描述了猪链球菌血清型2的多种毒力因子,但是缺乏明确的定义来确定哪些是真正的“关键”,这导致了矛盾,直到最近才被强调。在本文中,使用属于重要序列类型的原型菌株,针对不同归因功能评估了先前描述为对猪链球菌血清型2毒力至关重要的两个因素的参与,即二肽基肽酶IV和自溶素。结果表明,以前发布的数据缺乏可重复性。实际上,无法确认二肽基肽酶IV和自溶素作为关键毒力因子的作用。尽管某些体外功能可能归因于这些因素,但它们的作用并不是猪链球菌所独有的,可能是由于其他因素的补偿。因此,实验设计(包括体外测定,细胞系和动物模型)的变异和差异是结果差异的重要来源。此外,在这项研究中使用不同的序列类型表明,毒力因子的作用可能会因猪链球菌血清型2菌株背景而异。因此,有必要根据实验和目的建立标准的实验设计,以利于实验室之间的比较。同时,研究应包括不同来源的菌株,以防止可能影响未来研究的错误和偏颇的结论。

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