Bacteriophage diversity, dynamics, function, and exploitation
噬菌体多样性、动态、功能和利用
基本信息
- 批准号:10615099
- 负责人:
- 金额:$ 45.4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-05-01 至 2024-04-30
- 项目状态:已结题
- 来源:
- 关键词:Actinobacteria classAddressBacteriaBacterial Antibiotic ResistanceBacterial InfectionsBacterial PhysiologyBacteriophagesBioinformaticsBiologicalBiotechnologyClinicalClustered Regularly Interspaced Short Palindromic RepeatsCodeCollectionDevelopmentDiseaseEnvironmentEvolutionGenesGeneticGenomeGenome engineeringGenomicsHealthHumanInfectionInterventionMapsModificationMolecularMutateOrganismPathogenesisPlanetsPlayPopulationProphagesPublic HealthReproductionResistanceResourcesRiskRoleSpecificitySystemTherapeuticToxinTuberculosisVirus Diseasesantimicrobial drugcystic fibrosis patientsdynamical evolutionfightinggeochemistryglobal healthinnovationmicrobialmicrobial communitynon-tuberculous mycobacterial infectionnovel diagnosticsnovel therapeutic interventionnovel therapeuticspathogenpathogenic bacteriapressuretool
项目摘要
Bacteriophages are the most numerous biological entities on the planet. The phage population is enormously
dynamic, replacing itself through infection and reproduction every few days, and may be more than three billion
years old. Not surprisingly, they are enormously diverse genetically, although this diversity remains ill-defined
and only an extremely small part of the phage population has been genomically explored.
Bacteriophages play prominent roles in the environment, in human health, and in biotechnology. They are
implicated in many bacterial diseases by coding for toxins, and modulate bacterial physiology in a variety of
ways. Their diversity is generated in part by the highly dynamic microbial community in which there is
enormous selective pressure for bacteria to survive the constant onslaught of viral infections, and for the
phages to co-evolve by mutating to infect new bacterial hosts or evolving counter-defense systems that
overcome resistance. Among the defense systems that bacteria use to fight off phage infection are restriction-
modification and CRISPR-Cas systems, both of which have played revolutionary roles in biotechnology and
genome engineering. The huge impact of these derives in part from their extraordinary efficiency and
specificity, the consequences of three billion years of highly dynamic evolution.
The growing problem of widespread antibiotic resistance by bacterial pathogens presents a substantial global
health risk. Addressing this requires innovative strategies for new therapeutic approaches, and an aggressive
search for new antimicrobial agents. The prospects of bacteriophage therapy have been contemplated for
nearly 100 years, but has not found widespread use in the US. Diseases caused by pathogens in the phylum
Actinobacteria, including tuberculosis and NTM infections of Cystic Fibrosis patients, are notable public health
challenges, but any prospects for therapeutic phage interventions requires an understanding of the
determinants of phage host range and the mechanisms and specificity of phage resistance.
A large collection of over 13,000 phages infecting Actinobacterial hosts, 2,500 of which are completely
sequenced, provide a powerful resource for investigating phage diversity, phage genome evolution, phage host
range, bacterial-phage dynamics, and genetic and clinical tools for tuberculosis and NTM infections. Many of
these phages are temperate, and code for defense systems that are prophage-expressed and inhibit the
infection of lysogens by different (i.e. heterotypic) phages. These defense systems are highly varied and most
of the genes do not have bioinformatically predicted functions. Defense is often specific for a few subset of the
phages, but the mechanisms of targeting is not known.
The characterization of phage diversity, evolution, dynamics, and resistance will facilitate the development of
new diagnostic, preventative, and therapeutic approaches for bacterial infections.
噬菌体是地球上数量最多的生物实体。噬菌体的数量
每隔几天就通过感染和繁殖进行自我更新,数量可能超过30亿
岁毫不奇怪,他们在基因上有着巨大的多样性,尽管这种多样性仍然不明确
并且只有极少数噬菌体群体被基因组学研究。
噬菌体在环境、人类健康和生物技术中发挥着重要作用。他们是
通过编码毒素参与许多细菌性疾病,并在多种细菌中调节细菌生理学。
的方式它们的多样性部分是由高度动态的微生物群落产生的,
细菌在病毒感染的持续冲击下生存的巨大选择压力,
通过突变感染新的细菌宿主或进化出反防御系统,
克服阻力。细菌用来抵抗噬菌体感染的防御系统之一是限制性-
修饰和CRISPR-Cas系统,两者都在生物技术中发挥了革命性的作用,
基因工程它们的巨大影响部分来自于它们非凡的效率,
特异性,三十亿年高度动态进化的结果。
细菌病原体的广泛抗生素耐药性的日益严重的问题呈现出实质性的全球性问题。
健康风险。解决这一问题需要新的治疗方法的创新策略,以及积极的
寻找新的抗菌剂。噬菌体治疗的前景已被考虑,
近100年来,它一直没有在美国广泛使用。由门中病原体引起的疾病
放线菌,包括结核病和囊性纤维化患者的NTM感染,是值得注意的公共卫生
挑战,但任何治疗性噬菌体干预的前景都需要了解
噬菌体宿主范围的决定因素以及噬菌体抗性的机制和特异性。
大量收集了超过13,000种感染放线菌的宿主,其中2,500种完全
测序,为研究噬菌体多样性、噬菌体基因组进化、噬菌体宿主
范围,细菌噬菌体动力学,以及结核病和NTM感染的遗传和临床工具。许多
这些蛋白质是温和的,编码防御系统,这些防御系统是前噬菌体表达的,并抑制细胞增殖。
溶原菌被不同的(即异型的)细菌感染。这些防御系统种类繁多,
的基因不具有生物信息学预测的功能。防御往往是具体的几个子集,
但靶向机制尚不清楚。
噬菌体多样性、进化、动力学和抗性的表征将促进
新的诊断、预防和治疗细菌感染的方法。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Graham F. Hatfull其他文献
Stability and gene strand bias of lambda prophages and chromosome organization in emEscherichia coli/em
λ噬菌体的稳定性和基因链偏向性以及大肠杆菌中的染色体组织
- DOI:
10.1128/mbio.02078-23 - 发表时间:
2024-06-04 - 期刊:
- 影响因子:4.700
- 作者:
Xintian Li;Oscar Gallardo;Elias August;Bareket Dassa;Donald L. Court;Joel Stavans;Rinat Arbel-Goren;Graham F. Hatfull;Joshua S. Weitz - 通讯作者:
Joshua S. Weitz
Phage therapy: From biological mechanisms to future directions
噬菌体疗法:从生物学机制到未来方向
- DOI:
10.1016/j.cell.2022.11.017 - 发表时间:
2023-01-05 - 期刊:
- 影响因子:42.500
- 作者:
Steffanie A. Strathdee;Graham F. Hatfull;Vivek K. Mutalik;Robert T. Schooley - 通讯作者:
Robert T. Schooley
Evaluation of host immune responses to Mycobacteriophage Fionnbharth by route of delivery
- DOI:
10.1186/s12985-024-02552-2 - 发表时间:
2025-01-20 - 期刊:
- 影响因子:3.800
- 作者:
Thomas Smytheman;Tiffany Pecor;Dana E. Miller;Debora Ferede;Suhavi Kaur;Matthew H. Harband;Hazem F. M. Abdelaal;Carlos A. Guerrero-Bustamante;Krista G. Freeman;Whitney E. Harrington;Lisa M. Frenkel;Graham F. Hatfull;Rhea N. Coler;Sasha E. Larsen - 通讯作者:
Sasha E. Larsen
A new cell division operon inEscherichia coli
- DOI:
10.1007/bf02428043 - 发表时间:
1986-10-01 - 期刊:
- 影响因子:2.100
- 作者:
Deborah R. Gill;Graham F. Hatfull;George P. C. Salmond - 通讯作者:
George P. C. Salmond
Trehalose polyphleates participate in emMycobacterium abscessus/em fitness and pathogenesis
海藻糖多聚体参与脓肿分枝杆菌的适应性和发病机制
- DOI:
10.1128/mbio.02970-24 - 发表时间:
2024-11-13 - 期刊:
- 影响因子:4.700
- 作者:
Silke Malmsheimer;Wassim Daher;Yara Tasrini;Claire Hamela;John Jairo Aguilera-Correa;Christian Chalut;Graham F. Hatfull;Laurent Kremer - 通讯作者:
Laurent Kremer
Graham F. Hatfull的其他文献
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{{ truncateString('Graham F. Hatfull', 18)}}的其他基金
Bacteriophage diversity, dynamics, function, and exploitation
噬菌体多样性、动态、功能和利用
- 批准号:
10402332 - 财政年份:2019
- 资助金额:
$ 45.4万 - 项目类别:
Bacteriophage diversity, dynamics, function, and exploitation
噬菌体多样性、动态、功能和利用
- 批准号:
9908115 - 财政年份:2019
- 资助金额:
$ 45.4万 - 项目类别:
Mycobacteriophage as an emerging model organism
分枝杆菌噬菌体作为一种新兴的模式生物
- 批准号:
8077686 - 财政年份:2011
- 资助金额:
$ 45.4万 - 项目类别:
Mycobacteriophage as an emerging model organism
分枝杆菌噬菌体作为一种新兴的模式生物
- 批准号:
8260348 - 财政年份:2011
- 资助金额:
$ 45.4万 - 项目类别:
Construction and evaluation of next-generation reporter mycobacteriophages
下一代报告分枝杆菌噬菌体的构建和评估
- 批准号:
8475398 - 财政年份:2011
- 资助金额:
$ 45.4万 - 项目类别:
Construction and evaluation of next-generation reporter mycobacteriophages
下一代报告分枝杆菌噬菌体的构建和评估
- 批准号:
8078685 - 财政年份:2011
- 资助金额:
$ 45.4万 - 项目类别:
Construction and evaluation of next-generation reporter mycobacteriophages
下一代报告分枝杆菌噬菌体的构建和评估
- 批准号:
8269021 - 财政年份:2011
- 资助金额:
$ 45.4万 - 项目类别:
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