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。作为