PepSAVI-MS for discovery of novel botanical antimicrobial peptides

PepSAVI-MS 用于发现新型植物抗菌肽

• 批准号: 10572713
• 负责人: Leslie M. Hicks
• 金额: $ 6.8万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10572713
• 关键词: Address; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotic Therapy; Antibiotics; Antimicrobial Resistance; Bacteria; Bacterial Infections; Biological; Biological Assay; Biological Products; Biological Testing; Botanicals; Breathing; Characteristics; Chemicals; Chemistry; Clinical; Colistin; Community Hospitals; Coupled; Detection; Developing Countries; Drug Kinetics; Drug resistance; ESKAPE pathogens; Effectiveness; Enterobacteriaceae Infections; Environment; Evolution; Future; Goals; Heel; Hybrids; Informatics; Laboratories; Lead; Length; Libraries; Life; Mass Spectrum Analysis; Medicine; Metabolic; Methods; Microbe; Mining; Modernization; Modification; Molecular; Multi-Drug Resistance; Natural Products; Nature; Nosocomial Infections; Organism; Penetration; Peptides; Pharmaceutical Preparations; Pharmacology; Phenotype; Plant Extracts; Plants; Population; Post-Translational Protein Processing; Primary Health Care; Property; Proteins; Proteomics; Resources; Ribosomes; Savings; Signal Transduction; Soil; Source; Specificity; Statistical Models; Streptomycin; Techniques; Testing; Therapeutic; Tissues; Validation; Work; antimicrobial; antimicrobial drug; antimicrobial peptide; base; carbapenem-resistant Enterobacteriaceae; data handling; drug discovery; experimental study; falls; genome sequencing; immunogenicity; improved; infectious disease treatment; innovative technologies; instrumentation; knowledge base; lens; microbial; microorganism; novel; novel therapeutics; peptidomimetics; relative cost; scaffold; screening; small molecule therapeutics; therapy development

ABSTRACT The continued evolution of antimicrobial resistance emphasizes the dire need for discovery of antibiotic therapeutics with novel mechanisms of action. Technological advances in genome sequencing, drug library creation, and structural informatics have not advanced infectious disease treatments sufficiently. While natural products have long served as inspiration for novel therapeutic scaffolds, we posit peptide-derived entities offer great potential to address current needs due to their unique mechanisms of action, penetration and selectively. Herein, we describe our PepSAVI-MS pipeline to discover and characterize peptides with antimicrobial activity through implementation of a hybrid bioassay-guided/peptidomics platform. We directly identify botanical peptides contributing to bioactivity profiles using robust microbial bioassays optimized for peptide screening and using a mass spectrometry-based peptidomics approach coupled to statistical modeling and informatics to identify and further characterize these peptides at the molecular level. These potential lead compounds are then tested against an extensive panel of clinical ESKAPE pathogens, as well as for favorable drug characteristics and determination of mechanism-of-action. Our platform enables robust mining of plants and other natural sources for peptidyl species with unique or broad-spectrum anti-infective properties and has the potential to lead to the discovery of novel chemistries at the forefront of modern drug discovery.

摘要

项目成果

Exploring the Diversity of Cysteine-Rich Natural Product Peptides via MS/MS Fingerprint Ions.

• DOI: 10.1021/jasms.0c00078
• 发表时间: 2020-09-02
• 期刊: Journal of the American Society for Mass Spectrometry
• 影响因子: 3.2
• 作者: Parsley NC;Williams OL;Hicks LM
• 通讯作者: Hicks LM

Metabolomic characterization of Pseudomonas protegenssecretions for identification of biopesticides against Bacterial Panicle Blight of rice.

保护假单胞菌分泌物的代谢组学特征，用于鉴定抗水稻细菌性穗枯病的生物农药。

• 发表时间: 2022
• 期刊: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
• 作者: Balboa,SamanthaJ;Vierengel,Maia;Gates,Kristen;Rojas,Clemencia;Hicks,Leslie
• 通讯作者: Hicks,Leslie

The Greater Celandine: Identification and Characterization of an Antimicrobial Peptide from Chelidonium majus.

• DOI: 10.1021/acs.jnatprod.3c00939
• 发表时间: 2024-02
• 期刊: Journal of natural products
• 影响因子: 5.1
• 作者: Patric W. Sadecki;Garrett D Laws;Johnathon J Morgan;A. Wommack;R. Nawrot;Leslie M Hicks

Mass Spectrometric Identification of Antimicrobial Peptides from Medicinal Seeds.

• DOI: 10.3390/molecules26237304
• 发表时间: 2021-12-01
• 期刊: Molecules (Basel, Switzerland)
• 作者: Moyer TB;Brechbill AM;Hicks LM
• 通讯作者: Hicks LM

Implementation of Microfluidics for Antimicrobial Susceptibility Assays: Issues and Optimization Requirements.

• DOI: 10.3389/fcimb.2020.547177
• 发表时间: 2020
• 期刊: Frontiers in cellular and infection microbiology
• 影响因子: 5.7
• 作者: Parsley NC;Smythers AL;Hicks LM
• 通讯作者: Hicks LM