Inactivation of the CovR/S virulence regulator impairs infection in an improved murine model of Streptococcus pyogenes naso-pharyngeal infection.

Inactivation of the CovR/S virulence regulator impairs infection in an improved murine model of Streptococcus pyogenes naso-pharyngeal infection.
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CovR/S 毒力调节剂的失活会损害改良的化脓性链球菌鼻咽感染小鼠模型中的感染。

DOI:
10.1371/journal.pone.0061655
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Sriskandan S
Sriskandan S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Alam FM;Turner CE;Smith K;Wiles S;Sriskandan S

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化脓性链球菌是咽部感染的主要原因,估计每年有6.16亿例。人类鼻咽部是所有化脓链球菌感染的主要宿主,包括严重的侵袭性疾病。为了研究细菌和宿主因素对化脓性葡萄球菌感染的影响,我们设计了一种改进的小鼠鼻咽定植模型,优化了剂量体积以避免暴发性感染和敏感的宿主菌株。此外,我们还利用了一种非侵入性的细菌负荷纵向监测技术,从而减少了所需动物的数量。该模型用于证明CovR/S双组分调控系统是鼻咽部最佳感染和传播所必需的。covR/S突变具有鼻咽部特异性的适应度成本。这也许可以解释为什么covR/S改变的化脓链球菌在社区感染中没有流行,尽管在侵袭性感染中具有选择性优势。
Streptococcus pyogenes is a leading cause of pharyngeal infection, with an estimated 616 million cases per year. The human nasopharynx represents the major reservoir for all S. pyogenes infection, including severe invasive disease. To investigate bacterial and host factors that influence S. pyogenes infection, we have devised an improved murine model of nasopharyngeal colonization, with an optimized dosing volume to avoid fulminant infections and a sensitive host strain. In addition we have utilized a refined technique for longitudinal monitoring of bacterial burden that is non-invasive thereby reducing the numbers of animals required. The model was used to demonstrate that the two component regulatory system, CovR/S, is required for optimum infection and transmission from the nasopharynx. There is a fitness cost conferred by covR/S mutation that is specific to the nasopharynx. This may explain why S. pyogenes with altered covR/S have not become prevalent in community infections despite possessing a selective advantage in invasive infection.
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