BLRD Research Career Scientist Award Application

BLRD 研究职业科学家奖申请

• 批准号: 10337064
• 负责人: Andres Vazquez-Torres
• 金额: --
• 依托单位: VA EASTERN COLORADO HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-10-01 至 2025-09-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10337064
• 关键词: Alzheimer' s Disease; Amino Acids; Aminoglycoside resistance; Aminoglycosides; Anabolism; Antibiotic Resistance; Antibiotics; Award; Bacteremia; Bacteria; Bacterial Antibiotic Resistance; Binding; Blood; Burkholderia pseudomallei; Cell Wall; Cell division; Centers for Disease Control and Prevention (U.S.); Cessation of life; Clinical; Collaborations; Colorado; Complex; Complication; Cytochromes; DNA-Directed RNA Polymerase; Development; Diarrhea; Electron Transport; Enzymes; Escherichia coli; Evolution; Excretory function; Faculty; Family; Fostering; Funding; Genetic Transcription; Goals; Grant; Growth; Guanosine Tetraphosphate; HIV; Health; Healthcare Systems; Immunologic Deficiency Syndromes; Individual; Infection; Inflammation Mediators; International; Investigation; Journals; Knowledge; Legal patent; Mediating; Mediator of activation protein; Medical center; Mentors; Metabolic; Metabolic Pathway; Metabolism; Military Personnel; Mission; Molecular; Monitor; Monobactams; Multi-Drug Resistance; NADPH Oxidase; NOS2A gene; Nature; Nitric Oxide; Nucleotides; Oxidation-Reduction; Paper; Parkinson Disease; Pathogenesis; Patients; Persons; Phagocytes; Pharmaceutical Preparations; Play; Poison; Poisoning; Postdoctoral Fellow; Protein Biosynthesis; Proteins; Publishing; Purines; Regulation; Reporting; Research; Research Personnel; Research Project Grants; Resistance; Rod; Role; Salmonella; Salmonella infections; Sampling; Schedule; Science; Scientist; Secondary to; Seminal; Site; System; Training; Transcriptional Elongation Factors; Translating; Translations; Tubulin; Type III Secretion System Pathway; United States Department of Veterans Affairs; Universities; Veterans; Virulence; Wisconsin; Work; World Health Organization; absorption; antibiotic tolerance; antimicrobial; base; beta-Lactams; career; enteric pathogen; fundamental research; global health; graduate student; improved; macrophage; microbial; misfolded protein; next generation; novel; novel therapeutics; pathogen; pathogenic bacteria; preclinical study; programs; rational design; response; training opportunity; transcription factor

Salmonella infections are responsible for an estimated 3 million annual deaths worldwide. Multidrug resistance among clinical Salmonella more than doubled from 2011 to 2013. The World Health Organization has ranked Salmonella as one of the top 12 antibiotic resistant bacterial threats to global health. The goal of this Research Career Scientist Award is to continue with our efforts to apply our knowledge of Salmonella virulence to the development of novel antibiotics against multidrug resistant bacterial pathogens. Resistance of Salmonella and other pathogenic bacteria to antibiotics is in great part regulated by the nucleotide alarmone guanosine tetraphosphate and the DksA protein. Both of these mediators bind to the secondary channel of RNA polymerase, regulating transcription of central metabolic pathways and a variety of virulence programs. We will carry on our research on the molecular mechanisms by which guanosine tetraphosphate and DksA regulate Salmonella transcriptional programs. The Research Career Scientist Award will also allow us to develop novel antibiotics that inhibit DksA-dependent bacterial transcription. Binding of DksA to the secondary channel of RNA polymerase is in competition with Gre transcription elongation factors. We have found that Gre proteins are needed for Salmonella virulence and the resistance of this Gram-negative rod to antibiotics. We plan to characterize the molecular mechanisms by which Gre factors promote bacterial pathogenesis and antibiotic resistance. These research projects are highly collaborative in nature, involving scientific interactions with investigators at the Veterans Affairs Eastern Colorado Healthcare System, the Atlanta VA Medical Center and the Veterans Administration Ann Arbor Healthcare System. I plan to continue fostering these productive collaborations. Training of junior faculty, graduate students and postdoctoral fellows are also important components of this Research Career Scientist Award. Moreover, in collaboration with other investigators at the at the Veterans Affairs Eastern Colorado Healthcare System and Wisconsin-Madison VA Medical Center, we will continue mentoring promising CDA- 2 candidates, and thus help train the next generation of outstanding VA scientists.

据估计，全世界每年有300万人死于沙门氏菌感染。耐多药