Guo Lihong, McLean Jeffrey S, Lux Renate, He Xuesong, Shi Wenyuan
School of Dentistry, University of California, Los Angeles, CA90095, USA.
Department of Periodontics, University of Washington, Seattle, WA, 98195, USA.
Sci Rep. 2015 Dec 10;5:18015. doi: 10.1038/srep18015.
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.
变形链球菌被认为是导致龋齿的主要致龋菌。尽管人们认识到它们在龋病发生中的重要性,但对于变形链球菌的主要毒力因子(包括葡聚糖产生、产酸性和耐酸性)之间可能存在的协同作用,研究较少。在本研究中,我们使用表面展示有pH敏感型pHluorin的变形链球菌菌株,揭示了变形链球菌表面质子积累依赖于蔗糖可用性和葡糖基转移酶(Gtf)功能。与此一致的是,我们使用一种pH敏感染料证明,体内细胞产生的和体外酶促合成的不溶性葡聚糖都具有质子浓缩能力。全转录组学研究表明,质子积累以葡聚糖依赖的方式触发了编码参与耐酸反应功能的基因的上调。我们的数据表明,变形链球菌周围的这种质子富集可能使该细菌对酸应激产生预处理。与此假设一致的是,我们发现葡聚糖产生缺陷的变形链球菌菌株对酸更敏感。我们的研究首次揭示,不溶性葡聚糖可能是连接产酸性和耐酸性的关键因素。这些关键毒力因子的协同作用可能为变形链球菌如何成为主要致龋病原体提供新的见解。