The well-coordinated linkage between acidogenicity and aciduricity via insoluble glucans on the surface of Streptococcus mutans.
The well-coordinated linkage between acidogenicity and aciduricity via insoluble glucans on the surface of Streptococcus mutans.
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DOI：
10.1038/srep18015
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发表时间：
2015-12-10
影响因子：
4.6
通讯作者：
Shi W
中科院分区：
文献类型：
--
作者：
Guo L;McLean JS;Lux R;He X;Shi W
变形链球菌被认为是龋齿的主要致龋细菌。尽管人们认识到它们对致龋的重要性，但变形链球菌的主要毒力因子（包括葡聚糖产生、产酸性和酸尿性）之间可能的协调性尚未得到充分研究。在本研究中，使用具有表面显示 pH 敏感性 pHluorin 的变形链球菌菌株，我们揭示了变形链球菌表面上蔗糖可用性和 Gtf 功能依赖性质子积累。与此相一致的是，使用 pH 敏感染料，我们证明体内细胞产生的和体外酶法合成的不溶性葡聚糖都表现出质子浓缩能力。全球转录组学显示，质子积累会以葡聚糖依赖性方式触发编码参与耐酸反应的功能的基因上调。我们的数据表明，变形链球菌周围的质子富集可以使细菌预先适应酸应激。与这一假设一致，我们发现葡聚糖生产缺陷的变形链球菌菌株对酸更加敏感。我们的研究首次揭示，不溶性葡聚糖可能是连接产酸性和酸尿性的重要因素。这些关键毒力因子的协调可以为变形链球菌如何成为主要致龋病原体提供新的见解。
Streptococcus mutans is considered the principal cariogenic bacterium for dental caries. Despite the recognition of their importance for cariogenesis, the possible coordination among S. mutans’ main virulence factors, including glucan production, acidogenicity and aciduricity, has been less well studied. In the present study, using S. mutans strains with surface-displayed pH-sensitive pHluorin, we revealed sucrose availability- and Gtf functionality-dependent proton accumulation on S. mutans surface. Consistent with this, using a pH-sensitive dye, we demonstrated that both in vivo cell-produced and in vitro enzymatically synthesized insoluble glucans displayed proton-concentrating ability. Global transcriptomics revealed proton accumulation triggers the up-regulation of genes encoding functions involved in acid tolerance response in a glucan-dependent manner. Our data suggested that this proton enrichment around S. mutans could pre-condition the bacterium for acid-stress. Consistent with this hypothesis, we found S. mutans strains defective in glucan production were more acid sensitive. Our study revealed for the first time that insoluble glucans is likely an essential factor linking acidogenicity with aciduricity. The coordination of these key virulence factors could provide new insights on how S. mutans may have become a major cariogenic pathogen.