Nisin as a decontaminant for B. anthracis spores on human skin

描述(由申请者提供)：项目摘要：使用炭疽芽胞杆菌孢子的袭击或恐怖事件仍然是迫在眉睫的威胁。一旦发生这种攻击，包括人体皮肤在内的许多表面都会被散播的孢子污染。人体皮肤上携带的孢子不仅构成发展成皮肤炭疽病的威胁，而且还可能被带到远离发病地点的其他地方，从而导致孢子进一步传播。如果受孢子污染的人被运送到医院等地方，皮肤上脱落的孢子可能会影响虚弱的人，这可能会特别成问题。2001年事件的一个重要教训是，炭疽孢子的感染量可能比最初认为的要低得多，从人类皮肤上脱落的孢子可能会将疾病传播到远远超出最初攻击地点的地方。目前，还没有专门设计的产品来净化人体皮肤上的炭疽孢子。许多正在调查的去污方案都太苛刻，不能在皮肤上使用。Nisin是一种多肽抗生素，通常用作食品防腐剂，具有独特的防止细菌孢子萌发和生长的能力。Nisin结合在孢子表面，终止萌发过程，使孢子保持惰性和非传染性。Nisin通常被认为是安全的，目前用于动物身上以防止细菌感染。我们建议开发基于Nisin的配方，专门用于中和人体皮肤上的炭疽孢子。除了抗生素治疗和疫苗接种外，这些配方还打算用作另一层防御层。这个应用程序将选择Nisin和辅因子的最佳配方，以使用两种皮肤污染模型来净化炭疽孢子。我们还将研究Nisin对两种动物模型的预防作用；一种是研究创伤皮肤上孢子的萌发，另一种是用孢子肺攻击导致死亡。 相关性：该应用程序旨在开发一种专门设计用于净化人体皮肤上的炭疽孢子的产品。除抗生素和疫苗外，本产品还可用于防止受污染皮肤传播孢子和伤口感染炭疽热。目前，还不存在这样的产品。

DESCRIPTION (provided by applicant): Project summary: An attack or terrorist event using spores of Bacillus anthracis continues to be an imminent threat. In the event of such an attack, many surfaces including human skin will become contaminated with disseminated spores. Spores carried on human skin not only pose the threat of developing into cutaneous anthrax, but can also be carried to other locations distant from the attack site thereby leading to further spore dissemination. This can be particularly problematic if spore contaminated individuals are transported to locations like hospitals where spores shed from the skin may affect debilitated individuals. One important lesson from the events of 2001 is that the infectious dose of anthrax spores may be much lower than originally believed and spores shed from human skin could spread disease far beyond the initial location of an attack. Currently, there is no product specifically designed to decontaminate anthrax spores on human skin. Many of the decontamination regimens under investigation are too harsh for use on skin. Nisin is a peptide antibiotic that is commonly used as a food preservative and has the unique capacity to prevent the germination and outgrowth of bacterial spores. Nisin binds to the surface of the spores and terminates the germination process leaving the spores inert and non-infectious. Nisin is generally recognized as safe and is currently used topically on animals to prevent bacterial infections. We propose to develop nisin-based formulations specifically for neutralization of anthrax spores on human skin. These formulations are intended to be used in addition to antibiotic treatment and vaccination as another layer of defense. This application will select the best formulation of nisin and cofactors to decontaminate anthrax spores using two skin contamination models. We will also study the preventive effects of nisin on two animal models; one which studies germination of spores on wounded skin and one in which pulmonary challenge with spores induces death. Relevance: This application aims to develop a product which is specifically designed to decontaminate anthrax spores on human skin. This product is intended to be used in addition to antibiotics and vaccinations to prevent spread of spores by contaminated skin and anthrax infections of wounds. Currently, no such product exists.