Streptococcus mutans adaptation to oxidative stress by the Cid/Lrg system

 描述（由申请方提供）：变形链球菌被认为是人类龋齿的主要病原体。生物体在各种有害或应激条件下存活的能力以及作为稳定的口腔生物膜群落的数量上显著的成员出现的能力是S的持久性和致龋性的基本要素。变种人这种能力对于了解这种生物体如何在特定的生态位中定植和持续存在至关重要，并且可能与复杂的适应机制相互关联，这些机制允许生物体在动态的口腔微生物群落中保持稳态。这是S.在本研究中，将通过研究同源的LrgAB和lrgAB操纵子来研究变异链球菌的生理学，最近发现它们在S.变形杆菌在氧气中的生长，以及在各种关键S.变形杆菌毒力性状，包括自溶、生物膜形成、氧化和热应激以及遗传能力。更重要的是，cid和lrg操纵子被预测为类似于噬菌体编码的holin/antiholin蛋白（建议控制噬菌体介导的细胞死亡和裂解的活性）。本研究的目标是：1）破译cid和lrg基因之间的调控反馈的相互调控回路，2）识别 并表征S.中Cid/Lrg介导的细胞和分子机制。（3）评价Cid和Lrg对S. mutans竞争适合度的贡献。体外和体内的变形菌。这些目标将促进我们对S.变形链球菌存在于生物膜中，其具有高度复杂的分化细胞群体和动态代谢过程，并且代表了细菌程序性细胞死亡研究的新途径，其将进一步促进与其他口腔链球菌和革兰氏阳性生物体相关的基础知识。此外，建立生物膜发展和细胞死亡/裂解之间的联系将提供另一个有价值的洞察抑制龋齿的开始或进展和改善治疗和疾病控制的可能性。

 DESCRIPTION (provided by applicant): Streptococcus mutans is considered the principal etiological agent of human dental caries. The ability of the organism to survive a variety of harmful or stressful conditions and to emerge as numerically significant member of stable oral biofilm communities are essential elements for the persistence and cariogenicity of S. mutans. Such abilities are critical to understand how this organism colonizes and persists in specific niches, and are likely to interconnect with sophisticated adaptation mechanisms that allow the organism to maintain homeostasis within the dynamic oral microflora. This important aspect of S. mutans physiology will be pursued in this proposal by studying the homologous cidAB and lrgAB operons, recently identified as being highly balanced and coordinated during S. mutans growth in oxygen, as well as shown to play a significant role in a variety of key S. mutans virulence traits, including autolysis, biofilm formation, oxidative and heat stress, and genetic competence. More importantly, the cid and lrg operons were predicted to be analogous to bacteriophage-encoded holin/antiholin proteins (suggested to control the activity of bacteriophage-mediated cell death and lysis). The goals of this proposal are 1) to decipher the reciprocal regulatory circuits of regulatory feedback between the cid and lrg genes, 2) to identify and characterize the Cid/Lrg-mediated cellular and molecular mechanisms in S. mutans, and 3) to evaluate contribution of Cid and Lrg to the competitive fitness of S. mutans in-vitro and in-vivo. These objectives will advance our understanding of how S. mutans persists in biofilms that harbor a highly complex population of differentiated cells and dynamic metabolic processes, and represent a new avenue of bacterial programmed cell death research that will further fundamental knowledge relevant to other oral streptococci and Gram-positive organisms. Furthermore, establishing a link between biofilm development and cell death/lysis will provide another valuable insight into inhibition of the initiation or progression of dental caries and possibilities for improved therapy and disease control.