Intracellular Radiation as a Novel Approach for Infection Treatment

描述（由申请人提供）：尽管有吸引力，电离辐射不能直接应用于细菌感染的治疗，因为细菌对辐射极其不敏感。细菌的致死辐射剂量至少是人体致死剂量的1000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耐药性，细胞内辐射本身或与抗生素联合使用可能成为杀死抗生素耐药细菌的有效手段。这项拨款的主要目标是通过精心设计的体外研究实现“概念验证”。该项目的成功为改进细菌感染及各种感染相关疾病的治疗提供了新的途径。公共卫生相关性：细胞内辐射作为感染治疗的新方法叙述性细菌对电离辐射具有抗性。细菌的致死辐射剂量（1,000 Gy至6,000 Gy）远远超过人体的全身致死剂量（5 Gy），因此限制了电离辐射在治疗抗生素耐药性方面的潜在应用。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耐药性，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.