EzrA, a cell shape regulator contributing to biofilm formation and competitiveness in Streptococcus mutans
EzrA, a cell shape regulator contributing to biofilm formation and competitiveness in Streptococcus mutans
复制标题
EzrA，一种有助于变形链球菌生物膜形成和竞争力的细胞形状调节剂
DOI：
10.1111/omi.12264
复制
发表时间：
2019-07-22
影响因子：
3.7
通讯作者：
Li, Jiyao
中科院分区：
文献类型：
--
作者：
Xiang, Zhenting;Li, Zongbo;Li, Jiyao
细菌细胞分裂是由微管蛋白同源物FtsZ启动的，FtsZ在细胞中组装成一个环状结构，以促进细胞分裂。在枯草芽孢杆菌（Bacillus subtilis）和金黄色葡萄球菌（Staphylococcus aureus）、模型棒和球菌的细胞分裂过程中，EzrA参与了ftsz -环动力学和细胞壁生物合成。然而，它在致病性链球菌中的作用在很大程度上仍然未知。本文通过构建以斯拉框架内缺失突变体，研究了以斯拉在人类龋齿的主要病原——变形链球菌中的作用。我们的数据显示，与野生型相比，ezrA突变体生长缓慢，细胞形状长度缩短，宽度扩大，表明细胞分裂延迟，肽聚糖生物合成异常。此外，FtsZ不规则地定位于分裂的ezrA突变细胞，形成角度分裂面，可能导致异常的细胞形状。此外，利用单物种蛀牙生物膜模型进行的研究表明，ezrA的缺失导致生物膜形成缺陷，细胞外多糖减少，三维生物膜结构改变。出乎意料的是，在双物种生态模型中，ezrA突变体对H2O2的耐受性大大降低，并且对一种共生物种——血链球菌的竞争力降低。综上所述，这些结果表明，EzrA在调节变形链球菌的细胞分裂和维持正常形态中起着关键作用，并且是其强大的生物膜形成和种间竞争所必需的。因此，在开发控制龋齿和其他生物膜相关疾病的药物中，EzrA蛋白代表了一个潜在的治疗靶点。
Bacterial cell division is initiated by tubulin homologue FtsZ that assembles into a ring structure at mid-cell to facilitate cytokinesis. EzrA has been identified to be implicated in FtsZ-ring dynamics and cell wall biosynthesis during cell division of Bacillus subtilis and Staphylococcus aureus, the model rod and cocci. However, its role in pathogenic streptococci remains largely unknown. Here, the role of EzrA was investigated in Streptococcus mutans, the primary etiological agent of human dental caries, by constructing an ezrA in-frame deletion mutant. Our data showed that the ezrA mutant was slow-growing with a shortened length and extended width round cell shape compared to the wild type, indicating a delay in cell division with abnormalities of peptidoglycan biosynthesis. Additionally, FtsZ irregularly localized in dividing ezrA mutant cells forming angled division planes, potentially contributing to an aberrant cell shape. Furthermore, investigation using single-species cariogenic biofilm model revealed that deletion of ezrA resulted in defective biofilm formation with less extracellular polysaccharides and altered three-dimensional biofilm architecture. Unexpectedly, in a dual-species ecological model, the ezrA mutant exhibited substantially lower tolerance for H2O2 and reduced competitiveness against one commensal species, Streptococcus sanguinis. Taken together, these results demonstrate that EzrA plays a key role in regulating cell division and maintaining a normal morphology in S. mutans and is required for its robust biofilm formation/interspecies competition. Therefore, EzrA protein represents a potential therapeutic target in the development of drugs controlling dental caries and other biofilm-related diseases.