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.

数十年来，抗生素发现一直是天然产品（NP）研究的靶标。是 天然骑手反对细菌感染，细菌本身已证明是良好的抗生素生产者。 但是，由于广泛的探索，从冗余发现了来自细菌的NP发现。到 克服了这一点，已经发现了新方法，包括潜水员采样，培养条件筛查， 创新的代谢组检测技术以及基因组开采的使用来寻求新的生物活性 NPS。但是，建立细菌库的方式并没有太大变化，这是一个昂贵和人力的 所需的过程，这直接影响下游NP调查。在这项研究中，我们将采用工作流程 用于使用IDBAC管道对细菌菌株的优先排序，然后进行两种完整的方法（1）改进 传统的生物活性引导的NP隔离和（2）基于基因组学的研究以鉴定抗菌试剂 针对TB和Eskape病原体，尤其是在越南，抗生素抗性线。 通过分析的基质辅助激光解吸/电离质谱（MALDI-MS）指纹 生物信息学工具IDBAC，我们可以从水生和洞穴中产生最小重叠的细菌 环境作为NP发现的输入材料。在我们创新的双面琼脂板（DAPA）测定的指导下， 似乎抑制结核病和埃斯卡普病原体的菌株将随后提交传统隔离 识别活动组件的过程。此外，基因组采矿和福斯米德图书馆的一代将提供 阐明有希望的生物合成基因簇和编码的替代方法但完成的方法 TB和Eskape病原体的抗生素（以及药物靶标）。