Identification of antimicrobial reagents against TB and ESKAPE pathogens from bacteria collected in Vietnam

从越南收集的细菌中鉴定针对 TB 和 ESKAPE 病原体的抗菌试剂

• 批准号: 10225275
• 负责人: Linh Thuy Nguyen
• 金额: $ 12.97万
• 依托单位: --INSTITUTE OF MARINE BIOCHEMISTRY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-05 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10225275
• 关键词: Accounting; Address; Affect; Agar; Anabolism; Anti-Bacterial Agents; Antibiotic Resistance; Antibiotics; Antitubercular Agents; Bacteria; Bacterial Infections; Biochemical; Biological; Biological Assay; Chemicals; Complement; Country; Detection; Disease; Drug Targeting; ESKAPE pathogens; Environment; Evaluation; Fingerprint; Fluorescence; Gene Cluster; Generations; Genetic; Genome; Genomics; Human Development; Human Resources; Investigation; Lead; Libraries; Mass Spectrum Analysis; Methods; Microbe; Mining; Multidrug-Resistant Tuberculosis; Multiple Bacterial Drug Resistance; Mycobacterium tuberculosis; Natural Products; Pharmaceutical Preparations; Process; Reader; Reagent; Research; Resistance; Resistance development; Sampling; Side; Source; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Structure; Taxonomy; Tuberculosis; Vietnam; World Health Organization; antimicrobial; base; bioactive natural products; bioinformatics pipeline; bioinformatics tool; cost; detection method; global health; improved; innovation; metabolomics; microbial; microorganism; mutant; novel; novel strategies; open source; pathogen; pathogenic bacteria; programs; resistance gene; screening; tool

Antibiotics discovery has been the target of natural product (NP) investigation for decades. Being one of the natural rivals against bacterial infection, bacteria themselves have shown to be good antibiotic producers. However, due to extensive exploration, NP discovery from bacteria has been bottlenecked by redundancy. To overcome this, new approaches have been discovered including diverse sampling, culture condition screening, innovative metabolomic detection techniques as well as the usage of genome mining to seek for new bioactive NPs. However, there hasn’t much changed in the way of establishing bacterial library, a costly and manpower required process, which directly affects downstream NP investigation. In this study, we will employ a workflow for prioritizing bacteria strains using the IDBac pipeline followed by two complementary approaches (1) improved traditional bioactivity-guided NP isolation and (2) genomics-based studies to identify antimicrobial reagents against TB and ESKAPE pathogens, antibiotic resistance threads worldwide and in Vietnam in particular. Through analyzing matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) fingerprints using the bioinformatic tool IDBac, we can generate a minimum overlap set of bacteria from aquatic and cave environments as input materials for NP discovery. Guided by our innovative dual-sided agar plate (DAPA) assay, strains which appear to inhibit TB and ESKAPE pathogens will be subsequently submitted to traditional isolation processes to identify the active components. Moreover, genome mining and fosmid library generation will offer an alternative, yet complement, approach for elucidating promising biosynthetic gene clusters and the encoded antibiotics (as well as the drug targets) for TB and ESKAPE pathogens.

几十年来，抗生素的发现一直是天然产物（NP）研究的目标之一。 细菌是对抗细菌感染的天然对手，但事实证明细菌本身也是良好的抗生素生产者。 然而，由于广泛的探索，从细菌中发现纳米颗粒一直受到冗余的瓶颈。 克服这个问题，已经发现了新的方法，包括多样化采样、培养条件筛选、 创新的代谢组学检测技术以及使用基因组挖掘来寻找新的生物活性 然而，建立细菌库的方式并没有太大改变，成本和人力都很高。 所需的过程，这直接影响下游的 NP 研究，在本研究中，我们将采用一个工作流程。 使用 IDBac 管道优先考虑细菌菌株，然后采用两种互补方法 (1) 改进 传统的生物活性引导的 NP 分离和 (2) 基于基因组学的研究来鉴定抗菌试剂 对抗结核病和 ESKAPE 病原体，以及全世界尤其是越南的抗生素耐药性线索。 通过使用分析基质辅助激光解吸/电离质谱 (MALDI-MS) 指纹 生物信息学工具 IDBac，我们可以生成来自水生和洞穴的细菌的最小重叠集 在我们创新的双面琼脂板 (DAPA) 测定的指导下， 似乎能抑制 TB 和 ESKAPE 病原体的菌株随后将进行传统分离 此外，基因组挖掘和 fosmid 文库生成将提供识别活性成分的过程。 一种替代但补充的方法，用于阐明有前途的生物合成基因簇和编码的 针对 TB 和 ESKAPE 病原体的抗生素（以及药物靶点）。