J Infect Dis. 2014 Jul 1;210(1):25-34. doi: 10.1093/infdis/jiu058. Epub 2014 Jan 23.
Group A streptococcus (GAS) commonly colonizes the oropharynx and nonintact skin. However, colonization has been little studied and the role of biofilm formation is unclear, as biofilm experiments to date have not been conducted under conditions that mimic the host environment.
In this study we grew GAS biofilms on human keratinocytes under various environmental conditions and used this model to evaluate colonization, invasive disease and natural transformation.
GAS grown on epithelial cells, but not biofilms grown on abiotic surfaces, produced biofilms with characteristics similar to in vivo colonization. These biofilm bacteria showed a 100-fold higher bacterial burden of nasal-associated lymphoid tissue in mice than broth-grown bacteria, and were not virulent during septic infection, which was attributed in part to down-regulation of genes typically involved in localized and invasive disease. We also showed for the first time that GAS were naturally transformable when grown in biofilms and during colonization of NALT in vivo.
These findings provide novel model systems to study biofilm formation of GAS in vitro and in vivo, suggest an important role for biofilm formation during GAS colonization, and provide an explanation for the known genome diversity within the GAS population.
A 组链球菌(GAS)通常定植于口咽部和非完整皮肤。然而,定植现象研究较少,生物膜形成的作用也不清楚,因为迄今为止进行的生物膜实验并未在模拟宿主环境的条件下进行。
在这项研究中,我们在各种环境条件下使 GAS 在人角质形成细胞上形成生物膜,并使用该模型来评估定植、侵袭性疾病和自然转化。
在表皮细胞上生长的 GAS 形成生物膜,但在非生物表面上生长的生物膜则不能形成与体内定植相似的生物膜。与在肉汤中生长的细菌相比,这些生物膜细菌在小鼠鼻相关淋巴组织中的细菌负荷增加了 100 倍,在败血性感染期间也没有毒力,这部分归因于通常与局部和侵袭性疾病相关的基因下调。我们还首次表明,当 GAS 在生物膜中生长和在体内定植 NALT 时,GAS 具有自然转化能力。
这些发现为体外和体内 GAS 生物膜形成提供了新的模型系统,表明生物膜形成在 GAS 定植过程中具有重要作用,并为 GAS 群体中已知的基因组多样性提供了解释。