Molecular and Genetic Controls Regulating Bacterial Arsenite Oxidation

美国饮用水中砷浓度升高所带来的不可接受的健康风险，以及世界各国（如孟加拉国）砷中毒的流行程度，提高了国家和全球对控制土壤和水中砷的流动性和命运的环境进程的兴趣。砷的微生物生化转化对控制其在自然界中的运输、生物利用度和毒性至关重要。细菌会氧化亚砷酸盐[As(III)]或还原砷酸盐[As(V)]，以解毒或产生细胞能量。然而，对这些转化背后的生物化学和遗传学的理解过于简单，特别是在微生物如何感知或氧化砷（III）方面，从而限制了理解砷在环境中的行为的能力。目前的研究表明，双组分信号转导和群体感应共同调节编码As（III）氧化所必需的关键调控和功能活性的aox基因。该项目的重点是了解这些调节系统如何控制aox基因的表达，具体目标是：i)识别双组分蛋白AoxS和AoxR的传感器和信号转导成分；ii)确定如何感知As（III）信号；iii)鉴定所涉及的群体感应代谢物。就更广泛的影响而言，本研究的结果应适用于环境健康领域，并预计对指导旨在操纵某些农业、矿山复垦和市政水处理环境中微生物- as相互作用的补救工作具有价值。该研究还将通过为博士生和本科生研究实习生提供培训机会来影响人力资源开发，后者针对的是美洲原住民学生。此外，从这项研究中产生的知识将被整合到pi教授的本科和研究生课程中，以及在涉及小学，高中和科学非专业成人受众的教育推广活动中适当的参与者水平。

Unacceptable health risks associated with elevated arsenic concentrations in drinking water supplies in the United States and epidemic-level arsenic poisoning in countries worldwide (e.g. Bangladesh) have elevated national and global interest in environmental processes controlling the mobility and fate of arsenic in soil and water. Microbial biochemical transformations of arsenic are critically important to controlling its transport, bioavailability, and toxicity in nature. Bacteria will oxidize arsenite [As(III)] or reduce arsenate [As(V)] for either detoxification purposes or to generate cellular energy. However, understanding of the biochemistry and genetics underlying these transformations is overly simplistic, particularly in terms of how microorganisms sense or oxidize As(III), and thus constrains an ability to understand arsenic behavior in the environment. Current studies indicate that two-component signal transduction and quorum sensing co-regulate the aox genes that encode key regulatory and functional activities essential to As(III) oxidation. The focus of this project is to understand how the expression of the aox genes is controlled by these regulatory systems, with the specific aims being to: i) identify sensor and signal transduction components of the two-component proteins AoxS and AoxR; ii) determine how the As(III) signal is perceived; and iii) identify the quorum sensing metabolite(s) involved. In terms of broader impact, the results of this study should be applicable to the field of environmental health and are projected to be of value for guiding remediation efforts aimed at manipulating microbe-As interactions in certain agricultural, mine reclamation, and municipal water treatment settings. The research will also impact human resource development by providing training opportunities for a Ph.D. student and undergraduate research interns, with the latter targeting Native American students. Furthermore, knowledge generated from this study will be integrated into the undergraduate and graduate courses taught by the PIs, as well as at participant-appropriate levels in education-outreach activities that involve grade school, high school, and scientific-lay adult audiences.