Simultaneous Treatment of Viral and Bacterial Otitis Media Using Plant Natural Products
使用植物天然产品同时治疗病毒性和细菌性中耳炎
基本信息
- 批准号:10310502
- 负责人:
- 金额:$ 14.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-12-01 至 2023-11-30
- 项目状态:已结题
- 来源:
- 关键词:Active SitesAcuteAffectAlkaloidsAnabolismAnti-Bacterial AgentsAntibiotic ResistanceAntibioticsAntimicrobial EffectArtemisininsAuditory PhysiologyBacteriaBacterial Antibiotic ResistanceBacterial InfectionsBerberineBiochemistryBiologicalBiological AvailabilityBiological TestingBiologyCell Membrane PermeabilityCellsChargeChemicalsChildChild HealthChildhoodChinchilla (genus)CollaborationsComplexDevelopmentDiagnosisDiseaseDrug Delivery SystemsDrug resistanceEarEar DiseasesEffectivenessEngineeringEnhancersEnzymesExhibitsFormulationFutureGelGoldensealHealthHigh PrevalenceHuman bodyHydrogelsHydrophobicityIn VitroInfectionInvestigationIsoquinolinesKnowledgeLeadLeftLiquid ChromatographyLiquid substanceMedicinal PlantsMethodologyMicrobeModelingModificationMolecularNatural ProductsOpioidOtitis MediaPathway interactionsPermeabilityPersonsPharmaceutical PreparationsPharmacologic SubstancePlantsPreparationProductionPropertyRecurrenceResearchResistanceSiteSite-Directed MutagenesisSpeech DevelopmentStructureSystemTechniquesTemperatureTestingTherapeuticThickTissuesTreatment EfficacyTreatment outcomeTympanic membraneTyrosineUniversitiesViralVirusVirus DiseasesWorkYangYeastsantimicrobialbasebiomaterial compatibilitychemical functionchemical synthesiscytotoxicitydesignexperiencein vivoinnovationinsightknowledge basemethicillin resistant Staphylococcus aureusmicrobiomemiddle earmolecular sizenovelpathogenic bacteriapermanent hearing lossreconstructionscaffoldscreeningside effectsynthetic biologytreatment duration
项目摘要
1 Project Summary
2 Otitis media (OM) is a major child health burden. It is the most commonly diagnosed pediatric disease and the
3 #1 reason for antimicrobial prescription to US children. Moreover, 62% of children with OM demonstrate viral
4 infections in their middle ear, to which antibiotics are ineffective but prescribed nonetheless. The widespread use
5 of systemic antibiotics against a disease of such high prevalence and recurrence is believed to breed antibiotic
6 resistance. To treat viral and bacterial infections simultaneously, we will design and synthesize sophisticated
7 plant natural products (PNPs) and their derivatives with no known drug resistance,. The state-of-the-art synthetic
8 biology pipeline that we pioneered will enable the optimization and scalable production of antimicrobial PNPs
9 with enhanced permeability and antimicrobial efficacy. The novel PNP compounds will be delivered locally into
10 the middle ear using a proven hydrogel, which is an easy-to-apply liquid at room temperature and gels quickly
11 and firmly upon contacting warm tympanic membrane (TM). Chemical permeation enhancers inside the gel can
12 overcome the impermeable barrier of the TM and bring the PNPs into the middle ear. We have demonstrated
13 that a single application of the hydrogel formulation provides enough antibiotics for a 7-day treatment, eradicating
14 the infection in a chinchilla OM model.
15 The current application attempts to completely eliminate antibiotic usage in this prevalent childhood disease and
16 to mitigate OM-related drug resistance by using a stand-alone therapy that treats both bacterial and viral
17 infections. It focuses on the production and modification of berberine, an alkaloid derived from medicinal plants.
18 Berberine has demonstrated antimicrobial effects against Gram-positive and -negative bacteria including MRSA
19 and has shown antiviral properties against multiple viruses. This work will leverage our experience in PNP
20 biosynthesis to reconstruct a biosynthetic pathway in yeast for berberine production. We will incorporate diverse
21 tailoring enzymes (e.g., halogenases) and modified precursor molecules to produce modified berberine
22 derivatives that are difficult to achieve by conventional chemical synthesis. The therapeutic efficacy and
23 biocompatibility of the modified berberine derivatives will be tested using an established chinchilla OM model.
24 The knowledge and techniques developed in this project will provide new insight into overcoming the biological
25 barriers in the ear via molecular design and new treatments for acute and recurrent OM. The focus on berberine
26 is based on its known antimicrobial effect, and the general methodologies are applicable to other PNPs that
27 could treat ear diseases beyond OM.
1项目概述
项目成果
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{{ truncateString('SIJIN LI', 18)}}的其他基金
Simultaneous Treatment of Viral and Bacterial Otitis Media Using Plant Natural Products
使用植物天然产品同时治疗病毒性和细菌性中耳炎
- 批准号:
10115426 - 财政年份:2020
- 资助金额:
$ 14.7万 - 项目类别:
Simultaneous Treatment of Viral and Bacterial Otitis Media Using Plant Natural Products
使用植物天然产品同时治疗病毒性和细菌性中耳炎
- 批准号:
10530599 - 财政年份:2020
- 资助金额:
$ 14.7万 - 项目类别:
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