Antibacterial peptidoglycan recognition proteins

抗菌肽聚糖识别蛋白

• 批准号: 6801040
• 负责人: Roman Dziarski
• 金额: $ 37.63万
• 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/6801040
• 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率和死亡率的主要原因，而生物诱变A类和B病原体包括至少18种细菌，这些细菌在生物战或生物恐怖主义攻击中使用了对公共卫生的潜在威胁。这种攻击的暴露可能不涉及这些细菌传播的自然方式，而是可能涉及受污染的空气，物体，食物或供水。此外，将使用的生物战或生物恐怖剂最初可能不知道或可能是几种代理的混合物。因此，在宿主防御的早期防御这种攻击的早期，以防止或阻止进入入口处（可能是皮肤，眼睛，胃肠道和上呼吸道），可以在宿主防御的早期防御这种攻击的早期阶段，直接且基于广泛的保护是最有益的。由于对许多细菌的先天免疫机制的广泛特异性（通过其模式识别受体），先天免疫力可能是最初暴露后立即对抗此类细菌感染的最有效的第一道防线。因此，增强与细菌接触部位的宿主抗菌先天免疫，包括A类和B病原体，可以防止建立感染或补充其他疗法，从而在生物战或生物恐怖主义攻击中挽救生命。因此，该项目的目的是确定人类肽聚糖识别蛋白（PGRP）（PGRP）是新发现的抗菌模式识别分子的家族，可用于增强宿主防御细菌感染（包括生物脱脂型A类A和B类细菌病原体）。这种应用将首先需要了解其抗菌作用的机制。该项目将：首先，确定PGRP对多种细菌的抗菌活性程度（包括A类和B类细菌病原体）；其次，寻找具有较高抗菌活性的PGRP的替代剪接形式。第三，确定PGRP的抗菌作用的机制，并优化PGRP的抗菌作用的体外条件；第四，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位点时，PGRP在小鼠感染模型中是否具有保护性或治疗作用。