Structure and Function of the B. Anthracis Exosporium

炭疽杆菌外孢子的结构和功能

• 批准号: 7491642
• 负责人: CHARLES LEE TURNBOUGH
• 金额: $ 35.89万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7491642
• 关键词: Anthrax Vaccines; Anthrax disease; Antibiotics; Antibodies; Bacillus anthracis; Bacillus anthracis spore; Binding; Breathing; Cell Communication; Cells; Collagen; Development; Devices; Enzymes; Epitope Mapping; Epitopes; Future; Germination; Glycoproteins; Goals; Government; Growth; Host Defense; Immune system; Ingestion; Knowledge; Mutation; Play; Proteins; Reproduction spores; Resistance; Role; Site; Skin; Source; Stratum Basale; Structure; Surface; Surface Antigens; Tissues; United States; Virulence; day; design; hair-like nap; interest; mouse model; programs; response

Bacillus anthracis, the cause of anthrax, has been developed into a weapon of mass destruction by foreign governments and terrorist groups. The recent release of B. anthracis in the United States, with severe consequences, exposed the need for a more effective response to this threat. B. anthracis is used as a weapon largely because it forms highly resistant spores that can be incorporated into explosive weapons and terrorist devices. Spores enter the body through skin abrasions and by ingestion or inhalation and then germinate and grow as vegetative cells. When growth occurs in internal tissues, the host usually dies within several days. Natural strains of B. anthracis are sensitive to common antibiotics; however, large-scale use of these antibiotics to protect against anthrax is logistically difficult and medically dangerous. In addition, antibioticresistant strains may be used in the future. Furthermore, the current vaccine for anthrax has proven problematic. Thus, new strategies are needed to respond to the anthrax threat, and these are likely to require detailed knowledge of the interactions between the mammalian immune system and the outermost surface of the B. anthracis spore - the exosporium. The exosporium serves as the primary interactive site with host defenses, as the source of surface antigens, and as a semi-permeable barrier that excludes antibodies and destructive enzymes. The exosporium consists of a paracrystalline basal layer and an external hair-like nap. Approximately 50% of the mass of the exosporium appears to be proteins, roughly 20 unique species including glycoproteins. Preliminary studies indicate that exosporium proteins play a role in spore virulence. The goal of this project is to determine the content, structure, and function of the external surface of the exosporium. Of primary importance will be the role in virulence of surface-exposed proteins and glycoproteins. Specifically, we will (1) identify these proteins, make mutations that alter them, and examine the effects of the mutations on host-cell interactions and virulence using a mouse model. (2) We will map epitopes on key exosporium proteins, such as the collagen-like protein (BclA) of the hair-like nap, and examine the effects of antibody binding to these epitopes. Of special interest are antibodies that bind exosporium proteins and inhibit spore germination. (3) We will determine the structure of Bc1A and its domains. (4) We will examine the structure and assembly of the basal layer of the exosporium, including the attachment of the hair-like nap. The entire program project is designed to provide sufficient understanding of spore-host interactions to enable the development of new treatments for anthrax.

导致炭疽的炭疽芽孢杆菌已被外国政府和恐怖组织发展成为大规模杀伤性武器。最近在美国爆发的炭疽芽胞杆菌造成了严重后果，这表明需要对这一威胁作出更有效的反应。炭疽芽胞杆菌之所以被用作武器，主要是因为它能形成高度耐药的孢子，这些孢子可以被制成爆炸性武器和恐怖分子的装置。孢子通过皮肤擦伤和摄入或吸入进入人体，然后发芽并生长为营养细胞。当生长发生在内部组织时，宿主通常在几天内死亡。