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.

项目摘要/摘要伤寒是人类历史上最成功，最毁灭性的传染病之一，仍然存在一个严重的现实问题，每年杀死20万人，并患有2100万人。病因学剂伤寒是革兰氏阴性细菌沙门氏菌血清鼠Typhi（S. typhi），它是适应的仅针对人类。 S. Typhi的持续性 - 通行感染状态，以“伤寒玛丽”为例人对人的传播以及人类内细菌的继续维护。如果我们要有效地包含和射线座伤寒，我们需要实施抑制S. Typhi过渡的策略到持续的感染状态。但是，首先，我们必须了解S. Typhi如何促进急性过渡持续/托架感染状态。在人性化的鼠标模型中，该模型充当了S. typhi的持久性感染模型，伤寒毒素，一种由细胞内链球菌产生的独特的A2B5毒素或外毒素，已经是被鉴定为一种关键细菌确定剂，促进了链球菌感染向持续性的过渡感染状态。在此R01中，我们提出了一系列实验，以更好地了解伤寒毒素介导的促进伤寒链球菌持续感染的宿主细胞互动机制。拟议的研究可能会提供制定有效干预策略以更好地控制S. Typhi的关键信息传输和爆发。

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

Enteric Fever Diagnosis: Current Challenges and Future Directions.

DOI：
10.3390/pathogens10040410
发表时间：
2021-04-01
期刊：
Pathogens (Basel, Switzerland)
影响因子：
0
作者：
Neupane DP;Dulal HP;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

Delivery, structure, and function of bacterial genotoxins.