MINORITY PREDOCTORAL FELLOWSHIP PROGRAM

描述（由申请人提供）：细菌生物膜在医学上很重要，并且仍然占体内微生物感染的主要百分比。尽管在生物膜研究领域已经获得了大量的知识，但决定生物膜形成的发展和触发的调控机制才刚刚开始被阐明。据推测，细菌可能利用阳离子浓度来激活生物膜形成所需的机制；然而，关于这一过程的机制信息尚未获得。对生物膜表型改变的大肠杆菌突变体的基因筛选表明，钠泵调节剂NhaR在生物膜形成中起重要作用。此外，数据表明NhaR可能参与合成生物膜多糖粘附素所需的pgaABCD操纵子的激活。具体目标包括NhaR与pgaABCD操纵子相互作用的分子表征，长期目标是开始阐明NhaR和阳离子浓度在生物膜形成中的生理意义。

DESCRIPTION (provided by applicant): Bacterial biofilms are medically important and continue to account for a major percentage of microbial infections in the body. Although vast amounts of knowledge have been obtained in the field of biofilm research, the regulatory mechanisms that determine the development and triggering of biofilm formation are only starting to be elucidated. It has been hypothesized that bacteria might exploit cation concentrations to activate mechanisms required for biofilm formation; however, mechanistic information concerning this process has not been obtained. A genetic screen for mutants in E. coli with altered biofiolm phenotypes indicated that NhaR, a sodium pump regulator, plays an important role in biofilm formation. Moreover, data suggest that NhaR may be involved in the activation of the pgaABCD operon, required for synthesis of a biofilm polysaccharide adhesin. Specific aims include the molecular characterization of the interaction of NhaR with the pgaABCD operon with the long-term goal of beginning to elucidate the physiological significance of NhaR and cation concentration in biofilm formation.