Host-Directed Strategies to Create Synergistic Antibacterial Therapies

创建协同抗菌疗法的宿主导向策略

• 批准号: 9143637
• 负责人: JEFFERY S COX
• 金额: $ 78.5万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9143637
• 关键词: Acute; Anti-Bacterial Agents; Antibiotic Resistance; Antibiotics; Bacteria; Bacterial Infections; Cells; Chronic; Development; Drug resistance; Drug resistance in tuberculosis; Extreme drug resistant tuberculosis; Goals; Health; Immune; Infection; Infectious Agent; Molecular; Multi-Drug Resistance; Mycobacterium tuberculosis; National Security; Pathway interactions; Pharmaceutical Preparations; Process; Program Development; Resistance; Superbug; Time; Translating; global health; inhibitor/antagonist; man; novel; pathogen; programs; resistant strain; small molecule; success; vaccine efficacy

 DESCRIPTION (provided by applicant): Emerging antibiotic resistance is a global health crisis. From broadly resistant "superbugs" to extremely drug resistant Mycobacterium tuberculosis (XDR-TB), the specter of untreatable bacterial infection has become an alarming reality. The problem has become so acute that President Barack Obama recently issued an executive order calling multidrug resistant bacteria a national security priority. Likewise, the need to develop better antibiotics that shorten the treatment time to cure persistent bacterial infections also remains a major goal, especially for some of the most notorious pathogens of man, including M. tuberculosis. Due to the slow rate of new antibiotics emerging from the lab, countering antibiotic resistance and persistence by modifying existing drugs or developing inhibitors to new bacterial targets is unlikely to keep up with the increasing demand. The goal of this project is to take a radically different approach to new antibiotic development by identifying small molecules that target powerful host immune pathways of innate immune cells, creating adjunctive therapies that will synergize with conventional antibiotics. This approach is antithetical to traditional antibiotic development programs, which seek to identify molecular inhibitors that target essential pathways of the bacterium but avoid host pathways. The potential impact of "Host-Directed Therapies" (HDTs) could be dramatic, as they may re-sensitize drug-resistant strains and shorten the time to eradicate chronic infections. In particular, this proposa seeks to translate our understanding of host-pathogen interactions into a novel program for identifying small molecules targeting host processes that will synergize with traditional antibiotics during TB infection. The implications of success may extend beyond bacterial infection, as this approach could have huge implications for a broad range of infectious agents, and even boost vaccine efficacy.