Intracellular Radiation as a Novel Approach for Infection Treatment

描述（由申请人提供）：尽管电离辐射具有吸引力，但由于细菌对辐射极不敏感，因此不能直接用于治疗细菌感染。辐射对细菌的致死剂量至少比人体全身致死剂量高1,000倍。在这个R21项目中，我们提出了一种新的细胞内辐射方法来激活细菌内部的二次和局部辐射，以选择性和特异性地损伤染色体DNA。本项目的基本假设是：这种细胞内辐射可以克服细菌的辐射抗性，细胞内辐射本身或与抗生素联合使用可能成为杀灭抗生素抗性细菌的有效手段。该补助金的主要目标是通过精心设计的体外研究实现“概念验证”。该项目的成功可能为改善细菌感染和各种感染相关疾病的治疗提供新的方法。公共卫生相关性：细胞内辐射作为一种新的感染治疗方法叙述细菌对电离辐射有抵抗力。电离辐射对细菌的致死剂量（1，000戈伊~ 6，000戈伊）远远超过对人体的全身致死剂量（5戈伊），限制了电离辐射在抗生素耐药性治疗中的应用。在本项目中，我们提出了一种新的细胞内辐射方法来克服细菌的辐射抗性，并探索辐射在治疗细菌感染和各种感染相关疾病中的临床应用。

DESCRIPTION (provided by applicant): Despite attractive, ionizing radiations cannot be directly applied in the treatment of bacterial infections since bacteria are extremely insensitive to radiations. The lethal radiation dose for bacteria is at least 1,000 times higher than the whole-body lethal dose for human. In this R21 project, we propose a novel intracellular radiation approach to activate a secondary and local radiation inside of bacteria to damage chromosomal DNAs selectively and specifically. The underlying hypothesis of this project is that: this intracellular radiation can overcome the radiation resistance in bacteria, and the intracellular radiation by itself or in combination with antibiotics may become an effective means to kill antibiotic resistance bacteria. The primary goal of this grant is to achieve the "proof-of-concept" via well designed in vitro studies. The success of this project may provide a new approach for improved the treatment of bacterial infections and various infection related diseases. PUBLIC HEALTH RELEVANCE: Intracellular Radiation as a Novel Approach for Infection Treatment Narrative Bacteria is resistant to ionizing radiations. The lethal radiation dose (1,000 Gy to 6,000 Gy) for bacteria is far beyond the whole-body lethal dose for human (5 Gy) and thus limits the potential applications of ionizing radiation in the treatment of antibiotics resistance. In this project, we propose a novel intracellular radiation approach to overcome the radiation resistance in bacteria and explore the clinical applications of radiations in the treatment of bacterial infections and various infection related diseases.