Nasal Microbial Consortia Combat Antibiotic-Resistant Bacteria
鼻腔微生物联盟对抗抗生素耐药性细菌
基本信息
- 批准号:10357970
- 负责人:
- 金额:$ 40.04万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-03-01 至 2026-02-28
- 项目状态:未结题
- 来源:
- 关键词:16S ribosomal RNA sequencingAddressAdultAffectAirAntibiotic ResistanceApoptoticBacteriaBacterial Antibiotic ResistanceBacteriophagesBenignBiological AssayCell Culture TechniquesCessation of lifeChildClinical TrialsCoculture TechniquesCollectionColony-forming unitsCombating Antibiotic Resistant BacteriaCommunitiesCorynebacteriumDataEpithelialEpithelial AttachmentGenomeGrowthHumanImmune responseIn VitroInfectionInfection preventionInvadedKnowledgeLiquid substanceLyticMethodsMicroscopyMolecularMucous MembraneNasal EpitheliumNoseOrganoidsOutcomePermeabilityPersonsPhysiologyPopulationProductionReportingReproducibilityResistanceRiskSamplingSerotypingShapesSourceStaphylococcus aureusStreptococcus pneumoniaeSurfaceSystemTestingTherapeuticTight JunctionsTopical AntibioticVaccinesValidationVirulenceattenuationbasecolonization resistancecombatcytokineexperiencefluorescein isothiocyanate dextranimprovedinnovationmetabolomicsmicrobial hostmicrobiomemicrobiotanasal microbiomenasal microbiotanasal swabpathobiontpre-clinicalpreventrepairedresponsestem cell derived tissuestranscriptomicstransmission process
项目摘要
PROJECT SUMMARY: Project 3
The overall objective and significance of Project 3 is to generate preclinical validation of nasal microbiota-based
therapeutics to block nasal colonization by Staphylococcus aureus and Streptococcus pneumoniae. Our
innovative approach to achieve this is to cultivate human nasal bacteria on human nasal organoids. Together,
S. aureus and S. pneumoniae account for 39% of cases and 29% of deaths attributed to antibiotic-resistant
bacteria in the U.S. Nasal colonization is the primary source of invasive infection by each and the reservoir for
their transmission; blocking colonization reduces both infection and transmission. Lacking effective vaccines
against S. aureus or nonvaccine serotypes of S. pneumoniae, there is an urgent need for new nonantibiotic
approaches to prevent infections by both. Current therapies for nasal decolonization of S. aureus depend on a
topical antibiotic and are temporally correlated with rising antibiotic resistance. Here, we address a gap in
knowledge in how to repopulate with pathobiont-resistant microbiota to improve long-term outcomes. Multiple
nasal microbiota studies report benign bacterial species present when adults are free of S. aureus and when
children are free of S. pneumoniae. For example, nasal colonization by the benign bacterium Dolosigranulum
pigrum, often with harmless Corynebacterium, is associated with the absence of S. pneumoniae in children. In
adults, D. pigrum is inversely associated with S. aureus nasal colonization. Our preliminary data indicate many
strains of D. pigrum inhibit S. aureus growth in vitro. Also, cocultivation of D. pigrum with Corynebacterium
pseudodiphtheriticum robustly inhibits S. pneumoniae growth in vitro, versus either alone. Moreover,
Corynebacterium enhance D. pigrum growth. Thus, our overarching hypothesis is that reproducible consortia of
benign human nasal bacteria can confer colonization resistance to S. aureus and S. pneumoniae, preventing
infection by and transmission of these antibiotic-resistant threats. Moreover, antipathobiont mucosal-active lytic
phage may augment this. Networks of interactions underpin microbiota composition. Relying on consortia avoids
the risk of unexpected community interactions that can occur when adding a single strain and increases the
likelihood of successful repopulation with a desired community. A major hurdle to clinical trials is to identify fully
defined consortia of benign nasal bacterial strains that confer colonization resistance in the context of human
nasal epithelium and promote a healthy, intact epithelial barrier. Our Organoid Cultivation Core has successfully
generated human airway organoids. Thus, we will overcome this hurdle using advances in nasal epithelial
organoids combined with our expertise in cultivating human nasal bacteria and identifying molecular mechanisms
of interactions within nasal microbiota. With methods routinely used by us, Project 1 and the Organoid Cultivation
Core, we will achieve two aims: identify and characterize reproducible human nasal microbial consortia to 1)
protect nasal epithelium from colonization by S. aureus/S. pneumoniae and 2) to promote epithelial barrier
integrity and block epithelial invasion by S. aureus/S. pneumoniae in vitro, and identify underlying mechanisms.
项目总结:项目3
项目成果
期刊论文数量(0)
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科研奖励数量(0)
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Katherine Paige Lemon其他文献
Katherine Paige Lemon的其他文献
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{{ truncateString('Katherine Paige Lemon', 18)}}的其他基金
Mechanisms of Corynebacterium-Dolosigranulum Interactions that Shape Human Nasal Microbiota
棒状杆菌与多洛西颗粒相互作用塑造人类鼻腔微生物群的机制
- 批准号:
10378695 - 财政年份:2021
- 资助金额:
$ 40.04万 - 项目类别:
Nasal Microbial Consortia Combat Antibiotic-Resistant Bacteria
鼻腔微生物联盟对抗抗生素耐药性细菌
- 批准号:
10583470 - 财政年份:2021
- 资助金额:
$ 40.04万 - 项目类别:
Mechanisms of Corynebacterium-Dolosigranulum Interactions that Shape Human Nasal Microbiota
棒状杆菌与多洛西颗粒相互作用塑造人类鼻腔微生物群的机制
- 批准号:
10205817 - 财政年份:2021
- 资助金额:
$ 40.04万 - 项目类别:
Mechanisms of Corynebacterium-Dolosigranulum Interactions that Shape Human Nasal Microbiota
棒状杆菌与多洛西颗粒相互作用塑造人类鼻腔微生物群的机制
- 批准号:
10606509 - 财政年份:2021
- 资助金额:
$ 40.04万 - 项目类别:
Impact of Commensal Corynebacterium Species on Pathogen Colonization and Microbiota Composition
共生棒状杆菌物种对病原体定植和微生物群组成的影响
- 批准号:
10081046 - 财政年份:2016
- 资助金额:
$ 40.04万 - 项目类别:
Impact of commensal Corynebacterium species on pathogen colonization and microbiota composition
共生棒杆菌属对病原体定植和微生物群组成的影响
- 批准号:
9006947 - 财政年份:2016
- 资助金额:
$ 40.04万 - 项目类别:
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