A Genomics Based Investigation of the Determinants of Polymicrobial Infectious Disease Outcomes

基于基因组学的多种微生物传染病结果决定因素的研究

• 批准号: 10597144
• 负责人: CLAIRE M. FRASER
• 金额: $ 337.51万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10597144
• 关键词: Acute; Affect; Animals; Antifungal Agents; Antimalarials; Area; Bacteria; Bioinformatics; Biological; Biology; CRISPR/Cas technology; Cell Culture Techniques; Cells; Child; Childhood; Coculture Techniques; Communicable Diseases; Complex; Development; Disease; Disease Outcome; Disease model; Drug resistance; Ecosystem; Enrollment; Enteral; Evolution; Feces; Female; Foundations; Gastrointestinal tract structure; Gender; Gene Expression; Gene Expression Profile; Genes; Genetic; Genome; Genomics; Gnotobiotic; Goals; Health; Human; Immune response; Immune system; Individual; Infection; Integration Host Factors; Invaded; Investigation; Knowledge; Laboratories; Malaria; Maryland; Metagenomics; Microbe; Molecular; Nematoda; New York; Organism; Outcome; Parasites; Pathogenicity; Pathway interactions; Pharmaceutical Preparations; Plasmodium falciparum; Play; Primary Cell Cultures; Process; Published Comment; Research; Research Personnel; Research Project Grants; Respiratory System; Respiratory physiology; Role; Sampling; Scedosporium; Schistosoma haematobium; Sex Differences; Site; Sputum; Stimulus; Streptococcus pneumoniae; System; Technology; Testing; Toxic effect; Universities; Vaccines; Variant; Viral Genome; Viral Pathogenesis; Virulence; Virulence Factors; Virus; Virus Diseases; Work; antimicrobial; co-infection; commensal microbes; comparative; complex data; cross immunity; data integration; design; enteric pathogen; enteric virus infection; fungus; gene product; genome editing; genome sciences; high throughput technology; human subject; in vivo; influenzavirus; insight; male; medical schools; member; microbial genomics; microbiome analysis; microbiome components; microbiota; mouse model; multiple omics; new technology; new therapeutic target; nonhuman primate; normal microbiota; novel; pathogen; pathogenic bacteria; pathogenic fungus; pathogenic virus; priority pathogen; research and development; respiratory; single-cell RNA sequencing; stool sample; technology development; tool; transcriptomics; virome

The advent of high-throughput genomics and associated technologies have afforded the ability to begin to ask detailed questions about the biology of whole systems and the interactions of those parts, rather than examining parts of the system in isolation. This application contains studies that explore the dynamic interactions between pathogens, hosts, their microbiota and the immune system with the goal to provide a more comprehensive understanding of the determinants of infectious disease outcomes. Pathogens subvert host cells by using their gene products to manipulate cellular pathways for survival and replication; in turn, host cells respond to the invading pathogen through changes in gene expression. Deciphering these complex temporal and spatial dynamics to identify novel virulence factors or host response pathways is essential for complete understanding of the infectious disease process. However, even these approaches don't fully take into account the complexity of the interactions, given that the normal microbiota are also key players in these interactions. The majority of the members of the normal microbiota exist as mutualists that live in association with the host without causing disease. Yet, the interactions of a host, its microbiota, and a pathogen in the context of the host immune response, co-infections, anti-microbial therapies, or vaccines can greatly affect disease outcome. The integration of the high-throughput technology with the biological question highlights the evolution of genomics as an area of research from a strictly observational tool of only a few years ago, to being an integral part in the examination of the disease process and human health as a whole. The genomic viewpoint is becoming more complete, as we can begin to simultaneously characterize the interactions of host, pathogen and microbiota. The current application takes a systematic approach to the examination of not just a single pathogen, or the ecosystem that the pathogen is part of, but examines the impact of the other microbes and host factors on the infectious disease process. The integration of the data from these complex interactions is providing the foundation for a deeper understanding of health and disease. This proposal includes a highly collaborative group of investigators centered within the Institute for Genome Sciences at the University of Maryland and New York University who are experts in their respective areas of pathogen biology, but also are pioneers in the field of genomics. We expect that these studies will address major gaps in knowledge related to the molecular pathogenesis of viral, bacterial, fungal and parasitic pathogens.

高通量基因组学和相关技术的出现提供了开始发问的能力

项目成果

Persistence of Rare Salmonella Typhi Genotypes Susceptible to First-Line Antibiotics in the Remote Islands of Samoa.

• DOI: 10.1128/mbio.01920-22
• 发表时间: 2022-10-26
• 期刊: mBio
• 影响因子: 6.4

A possible role for fumagillin in cellular damage during host infection by Aspergillus fumigatus.

• DOI: 10.1080/21505594.2018.1526528
• 发表时间: 2018
• 期刊: Virulence
• 影响因子: 5.2
• 作者: Guruceaga X;Ezpeleta G;Mayayo E;Sueiro-Olivares M;Abad-Diaz-De-Cerio A;Aguirre Urízar JM;Liu HG;Wiemann P;Bok JW;Filler SG;Keller NP;Hernando FL;Ramirez-Garcia A;Rementeria A
• 通讯作者: Rementeria A

Genomic diversity of EPEC associated with clinical presentations of differing severity.

• DOI: 10.1038/nmicrobiol.2015.14
• 发表时间: 2016-01-18
• 期刊: NATURE MICROBIOLOGY
• 影响因子: 28.3
• 作者: Hazen, Tracy H.;Donnenberg, Michael S.;Panchalingam, Sandra;Antonio, Martin;Hossain, Anowar;Mandomando, Inacio;Ochieng, John Benjamin;Ramamurthy, Thandavarayan;Tamboura, Boubou;Qureshi, Shahida;Quadri, Farheen;Zaidi, Anita;Kotloff, Karen L.;Levine, Myron M.;Barry, Eileen M.;Kaper, James B.;Rasko, David A.;Nataro, James P.
• 通讯作者: Nataro, James P.

Genomic and Functional Characterization of Longitudinal Pseudomonas aeruginosa Isolates from Young Patients with Cystic Fibrosis.

• DOI: 10.1128/spectrum.01556-23
• 发表时间: 2023-08-17
• 期刊: MICROBIOLOGY SPECTRUM
• 影响因子: 3.7
• 作者: Chandler, Courtney E.;Hofstaedter, Casey E.;Hazen, Tracy H.;Rasko, David A.;Ernst, Robert K.
• 通讯作者: Ernst, Robert K.

Comparative Genomics of Atypical Enteropathogenic Escherichia coli from Kittens and Children Identifies Bacterial Factors Associated with Virulence in Kittens.

小猫和儿童非典型肠病性大肠杆菌的比较基因组学鉴定了与小猫毒力相关的细菌因素。

• DOI: 10.1128/iai.00619-20
• 发表时间: 2021
• 期刊: Infection and immunity
• 影响因子: 3.1
• 作者: Watson,VictoriaE;Hazen,TracyH;Rasko,DavidA;Jacob,MeganE;Elfenbein,JohannaR;Stauffer,StephenH;Gookin,JodyL
• 通讯作者: Gookin,JodyL