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Salmonella Typhi: Enhancement of Endemic Potential through its Unique Virulence Factors

伤寒沙门氏菌：通过其独特的毒力因子增强地方病的可能性

基本信息

批准号：
10543076
负责人：
Jeongmin Song
金额：
$ 58.14万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-12-21 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10543076
关键词：
Acetylation Acute Africa South of the Sahara Anabolism Antibiotic Therapy B-Lymphocytes Bacteria Cell Cycle Arrest Cell Death Cell Nucleus Cells Cessation of life Child Chronic Communicable Diseases Complex Cytoplasm DNA Damage Data Development Disease Outbreaks Endocytosis Environment Enzymes Etiology Exotoxins Gram-Negative Bacteria Human Infection Integration Host Factors Intervention Knowledge Leukopenia Lymphocyte Macrophage Maintenance Mediating Membrane Modeling Modification Molecular Mono(ADP-Ribose) Transferases Multi-Drug Resistance Organ Penetration Persons Polysaccharides Proteins Recording of previous events Regulation Research Role Salmonella Salmonella paratyphi Salmonella typhi Series Southeastern Asia Structure T-Lymphocyte Testing Toxin Typhoid Fever Vaccination Vacuole Vi capsular polysaccharide Virulence Factors acute infection chronic infection efficacious intervention experimental study extensive drug resistance extracellular global health holotoxins humanized mouse low and middle-income countries mouse model mutant neutrophil novel novel strategies nuclease pathogen prevent programs receptor binding receptor mediated endocytosis success trafficking transmission process vesicle transport

项目摘要

PROJECT SUMMARY/ABSTRACT Typhoid fever is one of the most successful and devastating infectious diseases in human history and remains a serious real-world problem that kills 0.2 million and sickens 21 million people every year. The etiological agent of typhoid fever is the gram-negative bacterium Salmonella enterica serovar Typhi (S. Typhi), which is adapted solely to humans. S. Typhi’s persistent-carriage infection state, exemplified by “Typhoid Mary,” is critical for person-to-person transmission and the continued maintenance of the bacterium within humans. If we are to effectively contain and eradicate typhoid fever, we need to implement strategies inhibiting S. Typhi’s transition to the persistent infection state. First, however, we must understand how S. Typhi facilitates transition from acute to a persistent/carriage infection state. In a humanized mouse model that serves as a S. Typhi’s persistent infection model, typhoid toxin, a distinct A2B5 toxin or exotoxin produced by intracellular S. Typhi, has been identified as a critical bacterial determinant facilitating the transition of S. Typhi infection to the persistent-carriage infection state. In this R01, we propose a series of experiments to better understand the typhoid toxin-mediated host cell interactive mechanism promoting S. Typhi’s persistent infection. The proposed research may provide critical information for the development of efficacious intervention strategies to better control S. Typhi’s transmission and outbreaks.

项目总结/摘要伤寒是人类历史上最成功和最具破坏性的传染病之一，这是一个严重的现实世界问题，每年造成20万人死亡，2100万人患病。病原伤寒的病原体是革兰氏阴性细菌伤寒沙门氏菌（S.伤寒），这是适应只对人类开放S.伤寒的持续携带感染状态，例如“伤寒玛丽”，人与人之间的传播和细菌在人体内的持续维持。如果我们要有效控制和消灭伤寒，我们需要实施抑制S.伤寒转变持续感染状态首先，我们必须了解S。伤寒易从急性持续/携带感染状态。在作为S.伤寒持续性感染模型、伤寒毒素、由细胞内S.伤寒，已经被鉴定为促进S.伤寒感染对持续带菌感染状态。在这个R 01中，我们提出了一系列的实验，以更好地了解伤寒毒素介导的宿主细胞相互作用机制促进S.伤寒持续感染。这项研究可能提供为制定有效的干预策略以更好地控制S.伤寒传播和爆发。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Direct IgG epitope mapping on bacterial AB toxins by cryo-EM.

DOI：
10.1016/j.xpro.2021.100852
发表时间：
2021-12-17
期刊：
STAR protocols
影响因子：
0
作者：
Nguyen T;Song J
通讯作者：
Song J

Complete Genome Sequence of Salmonella enterica Serovar Typhi Strain ISP2825.

DOI：
10.1128/mra.00804-21
发表时间：
2021-10-14
期刊：
Microbiology resource announcements
影响因子：
0.8
作者：
Lee GY;Song J
通讯作者：
Song J

Neutralization of Typhoid Toxin by Alpaca-Derived, Single-Domain Antibodies Targeting the PltB and CdtB Subunits.

DOI：
10.1128/iai.00515-21
发表时间：
2022-02-17
期刊：
Infection and immunity
影响因子：
3.1
作者：
Dulal HP;Vance DJ;Neupane DP;Chen X;Tremblay JM;Shoemaker CB;Mantis NJ;Song J
通讯作者：
Song J

Enteric Fever Diagnosis: Current Challenges and Future Directions.