Evaluating Antimicrobial Compounds from Coral-Associated Pseudovibrio Bacteria

评估珊瑚相关假弧菌的抗菌化合物

• 批准号: 7754720
• 负责人: Maria I. Vizcaino
• 金额: $ 3.88万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-03-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7754720
• 关键词: Actinobacteria class; Actinomyces; Address; Agar; Amines; Amino Acids; Anti-Bacterial Agents; Antibiotics; Antimicrobial Resistance; Bacteria; Biological Assay; Biological Factors; Biological Sciences; Carbon; Caribbean region; Cataloging; Catalogs; Cell physiology; Cells; Cholera; Coculture Techniques; Code; Collaborations; Communicable Diseases; Complex; Coupled; DNA; DNA Sequence; Databases; Detection; Development; Disease; Drug resistance; Ecosystem; Environment; Escherichia coli; Exhibits; Fractionation; Gas Chromatography; Genbank; Gene Cluster; Genes; Genetic; Glycosaminoglycans; Gram-Negative Bacteria; Growth; Habitats; Health; High Pressure Liquid Chromatography; Human; Infectious Agent; Invertebrates; Laboratories; Light; Liquid Chromatography; Malignant Neoplasms; Marines; Martens; Maryland; Metabolic; Metabolic Pathway; Methods; Microbial Antibiotic Resistance; Mission; Modeling; Molecular; Molecular Biology Techniques; Monitor; Multi-Drug Resistance; Names; National Institute of Allergy and Infectious Disease; Nuclear Magnetic Resonance; Organism; Pathogenicity; Pathway interactions; Peptides; Pharmaceutical Preparations; Pharmacologic Substance; Physiology; Pigments; Pollution; Porifera; Preparation; Prodigiosin; Production; Property; Protein Biosynthesis; Proteome; Pseudomonas aeruginosa; Public Health; Recombinant DNA; Reporting; Research; Resistance; Role; Screening procedure; Seawater; Soil; Source; Staphylococcus aureus; Streptomyces; Sugar Phosphates; Surface; Surveys; Techniques; Temperature; Testing; Universities; Urochordata; Variant; Vibrio; Vibrio cholerae; Work; World Health; analog; antimicrobial; antimicrobial peptide; austin; bacterial pigment; bacterial resistance; base; chemical property; climate change; clinical application; clinically relevant; combat; coral; drug development; drug discovery; fungus; genome sequencing; human disease; insight; marine organism; meetings; metabolomics; microbial; microbial community; microorganism; novel; pathogen; porin; sugar; tool

DESCRIPTION (provided by applicant): The search for novel antibiotics is of direct human health relevance because of the increase in microbial resistance to conventional antibiotics and a deficit in new drugs (1, 2). Coral reefs are the most biodiverse of marine ecosystems and a source of novel antibiotics, but they are threatened due to disease, climate change, and pollution (3). Since marine bacteria can produce compounds that are chemically distinct from their terrestrial counterparts (4), it is imperative to catalog and characterize the unknown microbial diversity in corals and their potential antibiotics. The main objectives of this work are to characterize antibiotics from marine bacteria associated with a coral, and to study the functional role of the antibiotic insult on a pathogen's physiology. The first aim will ascertain the antimicrobial activity of bacteria isolated from Pseudopterogorgia americana surface mucopolysaccharide layer (SML), which is a carbon-rich habitat for an abundant and diverse microbial community (5). The SML selects for symbiotic bacteria with antimicrobial activity that may protect the coral host by detemng pathogenic microorganisms (6, 7). We will use an agar- overlay antimicrobial assay to determine the antimicrobial production of P. americana's SML-associated bacteria against seven microorganisms relevant to human and corals. The second aim specifically targets NIAID/NIH's mission for drug discovery by identifying and characterizing antimicrobial compounds from a broad-spectrum antimicrobial coral isolate, and surveying its genetic bioactive potential with molecular techniques. Antibiotic compound(s) will be purified and structurally characterized using chromatographic (e.g., HPLC), mass spectrometric (e.g., LC-MS), and spectroscopic (NMR) techniques. Molecular techniques will be performed to determine presence of genes known to produce bioactive compounds. The third aim will analyze a possible mechanism of antibiotic action against a coral pathogen through metabolic profile characterization of its co-culture with the antimicrobial coral isolate. We will utilize metabolomics to analyze the intracellular changes of a Vibrio pathogen when in presence of an antimicrobial coral isolate, focusing on metabolic changes (e.g., DNA, RNA, protein synthesis) using NMR analysis. Relevance- The World Health Report categorized microbial antibiotic resistance as a major threat to public health, which is augmented due to the diminished developmental research for new antibiotic drugs (8). This project seeks to meet this demand by characterizing potentially novel antibiotic(s) and their function on a microbial pathogen's physiology.

描述（由申请人提供）：由于微生物对常规抗生素的耐药性增加和新药短缺，寻找新型抗生素与人类健康直接相关（1,2）。珊瑚礁是最具生物多样性的海洋生态系统，也是新型抗生素的来源，但它们受到疾病、气候变化和污染的威胁(3)。由于海洋细菌可以产生与陆地细菌在化学上不同的化合物(4)，因此必须对珊瑚中未知的微生物多样性及其潜在的抗生素进行分类和表征。这项工作的主要目的是表征与珊瑚相关的海洋细菌的抗生素，并研究抗生素对病原体生理的功能作用。第一个目的是确定从美洲假紫杉表面粘多糖层（SML）中分离的细菌的抗菌活性，这是一个丰富多样的微生物群落的富碳栖息地(5)。SML选择具有抗菌活性的共生细菌，可以通过检测致病微生物来保护珊瑚宿主（6,7）。我们将使用琼脂覆盖抗菌试验来确定美洲p.a americana的sml相关细菌对7种与人类和珊瑚相关的微生物的抗菌产量。第二个目标专门针对NIAID/NIH的药物发现任务，通过从广谱抗菌珊瑚分离物中鉴定和表征抗菌化合物，并用分子技术测量其遗传生物活性潜力。抗生素化合物将使用色谱（如HPLC）、质谱（如LC-MS）和波谱（NMR）技术进行纯化和结构表征。分子技术将用于确定已知产生生物活性化合物的基因的存在。第三个目标将通过其与抗菌珊瑚分离物共培养的代谢特征来分析抗生素作用于珊瑚病原体的可能机制。当存在抗菌珊瑚分离物时，我们将利用代谢组学分析弧菌病原体的细胞内变化，重点关注使用核磁共振分析的代谢变化（例如，DNA， RNA，蛋白质合成）。相关性-《世界卫生报告》将微生物抗生素耐药性归类为对公共卫生的主要威胁，由于新的抗生素药物开发研究的减少，这一威胁得到了加强(8)。本项目旨在通过表征潜在的新型抗生素及其对微生物病原体的生理功能来满足这一需求。