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

乳链菌肽作为人体皮肤上炭疽芽孢杆菌孢子的净化剂

• 批准号: 7201607
• 负责人: Kenneth Alibek
• 金额: $ 31.16万
• 依托单位: AFG BIOSOLUTIONS, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-15 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7201607
• 关键词: Affect; Animal Model; Animals; Anthrax disease; Antibiotic Therapy; Antibiotics; Area; Bacillus anthracis; Bacillus anthracis spore; Bacterial Infections; Bacterial Spores; Binding; Cessation of life; Cream; Cutaneous; Decontaminant; Decontamination; Development; Disease; Distant; Dose; Drug Formulations; Event; Family suidae; Food Preservatives; Germination; Hospitals; Human; In Vitro; Inbred HRS Mice; Individual; Infection; Investigation; Left; Location; Lung; Mediating; Modeling; Mus; Nisin; Paper; Peptide Antibiotics; Peptides; Phase; Preventive; Primary Health Care; Process; Relative (related person); Reproduction spores; Resistance; Site; Skin; Surface; Sus scrofa; Testing; Therapeutic; Time; Treatment Protocols; Vaccination; Variant; Work; Wound Infection; base; cofactor; design; emergency service responder; follow-up; macrophage; nisin A; prevent

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.

描述（由申请人提供）：项目摘要：使用炭疽芽孢杆菌孢子的袭击或恐怖事件仍然是迫在眉睫的威胁。在这种攻击的情况下，包括人类皮肤在内的许多表面将被传播的孢子污染。人类皮肤上携带的孢子不仅构成发展成皮肤炭疽的威胁，而且还可以携带到远离袭击地点的其他地方，从而导致孢子进一步传播。如果孢子污染的个体被运送到像医院这样的地方，在那里孢子从皮肤脱落可能影响虚弱的个体，这可能是特别有问题的。2001年事件的一个重要教训是，炭疽孢子的传染剂量可能比最初认为的要低得多，从人体皮肤上脱落的孢子可以将疾病传播到远远超出最初攻击地点的地方。目前，还没有专门设计用于净化人体皮肤上炭疽孢子的产品。许多正在研究的去污方案对皮肤来说太苛刻了。乳链菌肽是一种肽类抗生素，通常用作食品防腐剂，具有防止细菌孢子萌发和生长的独特能力。乳链菌肽与孢子表面结合并终止萌发过程，使孢子呈惰性且无感染性。乳链菌肽通常被认为是安全的，目前被局部用于动物，以防止细菌感染。我们建议开发基于乳酸链球菌素的配方，专门用于中和人体皮肤上的炭疽孢子。这些制剂旨在作为抗生素治疗和疫苗接种的另一层防御。本申请将使用两种皮肤污染模型来选择乳链菌肽和辅因子的最佳配方以净化炭疽孢子。我们还将研究乳酸链球菌素对两种动物模型的预防作用;一种是研究孢子在受伤皮肤上的萌发，另一种是用孢子进行肺部攻击诱导死亡。 相关性：该申请旨在开发一种专门用于净化人体皮肤上炭疽孢子的产品。本产品旨在与抗生素和疫苗一起使用，以防止孢子通过受污染的皮肤传播和伤口炭疽感染。目前还没有这样的产品。