Evolution of Bacterial Copper Resistance

9306559 Cooksey本项目旨在研究植物相关细菌如何适应环境中有毒水平的铜。 铜是一种重要的农药，常用于农业植物病害的防治。 植物病原细菌对铜的抗性发展可能对未来铜在植物病害防治中的应用构成威胁，更好地了解这种抗性的发展对于评估这种威胁将是重要的。 对铜抗性的认识已经导致人们尝试开发可能规避抗性机制的新铜制剂，并且更好地理解抗性的生理和调节机制可以加强这一努力。微生物对非必需的有毒金属（如汞）的抗性已得到广泛研究，但对铜的抗性受到的关注要少得多。 与其他金属不同。铜作为某些酶的组成部分，是生物体所必需的;低水平的铜是有益的，但高水平的铜是有毒的。 因此，微生物种群中铜抗性的演变涉及铜吸收和排斥机制的复杂平衡。 克隆和鉴定了决定铜抗性的基因，发现它们与在铜敏感细菌中发现的一组染色体基因相关。 我们已经证明，通过这些染色体基因的修饰，可以进化出耐药性，目前的项目是进一步定义这些修饰。 由于铜是微生物所需的微量元素，因此阻止铜吸收的抗性机制必须处于严格的监管控制之下，以便在正常生长条件下不排除铜。 我们有证据表明在这个系统中基因表达水平的改变。 细菌产生的其他蛋白质的铜结合能力在铜排斥机制中很重要，我们将研究这些蛋白质的铜结合位点在抗性进化过程中如何被修饰。

9306559 Cooksey This project is to investigate how plant associated bacteria adapt to toxic levels of copper in the environment. Copper is an important bactericide used frequently for disease control on agricultural plants. The development of copper resistance in plant pathogenic bacteria may pose a threat to the future use of copper in plant disease control, and a better understanding of how this resistance develops will be important for evaluating this threat. The recognition of copper resistance has already led to attempts to develop new copper formulations that may circumvent resistance mechanisms, and a greater understanding of the physiological and regulatory mechanisms of resistance could enhance that effort. %%% Microbial resistance to nonessential toxic metals, such as mercury, has been studied extensively, but resistance to copper has receives much less attention. Unlike the other metals. copper is required by loving organisms as a component of certain enzymes; at low levels it is beneficial, but at high levels it is toxic. The evolution of copper resistance in microbial populations therefore involves a complex balance in copper uptake and exclusion mechanisms. The genes determining copper resistance were cloned and characterized, and they were found to be related to a set of chromosomal genes found in copper sensitive bacteria. We have shown that the resistance can evolve through modifications of these chromosomal genes, and the present project is to define further these modifications. Since copper is required by microorganisms as a trace element, the resistance mechanism, which prevents uptake of copper, must be under tight regulatory control so that copper is not excluded under normal growth conditions. We have evidence that modifications in the level in gene expression in this system. The copper binding capacity of other proteins produced by the bacterium is important in the copper exclusion mechanism, and we will study how copper binding sites of these proteins have been modified during the evolution of resistance.