Antibacterial peptidoglycan recognition proteins

抗菌肽聚糖识别蛋白

• 批准号: 7049335
• 负责人: Roman Dziarski
• 金额: $ 36.74万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7049335
• 关键词: Bacillus anthracis; Burkholderia; Campylobacter; Listeria; Yersinia pestis; antibacterial agents; bacteria infection mechanism; bacterial proteins; bacteriolysis; complementary DNA; cooperative study; gastrointestinal system; host organism interaction; in situ hybridization; laboratory mouse; mucosa; northern blottings; peptidoglycan; polymerase chain reaction; respiratory system

DESCRIPTION (provided by applicant): Bacterial infections are still a major cause of morbidity and mortality, and biodefense category A and B pathogens include at least 18 bacteria that are potential threats to public health in case of their use in biological warfare or bioterrorism attack. The exposure from such an attack may not involve natural ways of transmission of these bacteria, but rather would likely involve contaminated air, objects, food, or water supply. Furthermore, the biological warfare or bioterrorism agent that will be used may not be initially known or may be a mixture of several agents. Therefore, an immediate and broad-based protection, effective against many bacteria, would be most beneficial in early stages of host defense against such an attack, to prevent or stop the infection at the portal of entry (which is likely to be skin, eyes, gastrointestinal tract, and upper respiratory tract). Because of broad specificity of innate immunity mechanisms for many bacteria (through their pattern recognition receptors), innate immunity is likely to be the most effective first line of defense to combat such bacterial infections immediately after the initial exposure. Thus, enhancing host antibacterial innate immunity at the site of contact with bacteria, including category A and B pathogens, could prevent establishment of infection or complement other therapies, and thus save lives in a biological warfare or a bioterrorism attack. Therefore, the goal of this project is to determine if human peptidoglycan recognition proteins (PGRPs), a newly discovered family of antibacterial pattern recognition molecules, can be applied to enhance host defenses against bacterial infections (including biodefense category A and B bacterial pathogens). Such an application will first require understanding of the mechanism of their antibacterial effect. This project will: first, determine the extent of antibacterial activity of PGRPs against a variety of bacteria (including category A and B bacterial pathogens); second, look for alternative splice forms of PGRPs with higher antibacterial activity; third, determine the mechanism of antibacterial effect of PGRPs and optimize the in vitro conditions for the antibacterial effect of PGRPs; and fourth, determine if PGRPs have protective or therapeutic effects in mouse infection models, when applied to the initial site of contact with selected category A and B bacterial pathogens.

描述（由申请人提供）：细菌感染仍然是发病和死亡的主要原因，生物防御 A 类和 B 类病原体包括至少 18 种细菌，如果将其用于生物战或生物恐怖袭击，会对公众健康构成潜在威胁。此类攻击的暴露可能不涉及这些细菌的自然传播方式，但很可能涉及受污染的空气、物体、食物或供水。此外，将使用的生物战剂或生物恐怖主义剂可能最初并不知道，或者可能是几种试剂的混合物。因此，立即和广泛的保护，有效对抗许多细菌，在宿主防御此类攻击的早期阶段是最有益的，以防止或阻止入口处（可能是皮肤、眼睛）的感染。 、胃肠道和上呼吸道）。由于许多细菌的先天免疫机制具有广泛的特异性（通过其模式识别受体），先天免疫可能是在初次接触后立即对抗此类细菌感染的最有效的第一道防线。因此，增强宿主与细菌（包括 A 类和 B 类病原体）接触部位的抗菌先天免疫力，可以防止感染的发生或补充其他疗法，从而在生物战或生物恐怖袭击中拯救生命。因此，该项目的目标是确定人类肽聚糖识别蛋白（PGRP）这一新发现的抗菌模式识别分子家族是否可以应用于增强宿主对细菌感染（包括生物防御A类和B类细菌病原体）的防御。这种应用首先需要了解其抗菌作用的机制。该项目将：首先确定PGRP对多种细菌（包括A类和B类细菌病原体）的抗菌活性程度；其次，寻找具有更高抗菌活性的PGRP的替代剪接形式；第三，确定PGRPs抗菌作用机制，优化PGRPs体外抗菌条件；第四，确定当将 PGRP 应用于与选定的 A 类和 B 类细菌病原体的初始接触部位时，其在小鼠感染模型中是否具有保护或治疗作用。