Regulation and role of Salmonella curli during chronic infection

卷曲沙门氏菌在慢性感染过程中的调节和作用

• 批准号: 10219076
• 负责人: JOHN S GUNN
• 金额: $ 23.1万
• 依托单位: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-17 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10219076
• 关键词: Address; Alzheimer' s Disease; Amyloid; Amyloid Proteins; Animals; Antibiotics; Bacteria; Bile fluid; Carrier State; Cellulose; Cessation of life; Cholelithiasis; Chronic; Clinical; Communicable Diseases; Complex; DNA; Data; Defect; Development; Disease; Enteral; Enterobacteriaceae; Environment; Escherichia coli; Extracellular Matrix; Fiber; Future; Gallbladder; Gastroenteritis; Gene Activation; Gene Expression; Gene Expression Regulation; Genes; Goals; Human; Immune; Immune response; Immune system; Immunity; In Vitro; Individual; Infection; Inflammation; Kenya; Knowledge; Life; Link; Maintenance; Mediating; Methods; Microbial Biofilms; Modeling; Molecular; Morbidity - disease rate; Mus; Organ; Outcome; Pattern recognition receptor; Phenotype; Pilum; Polysaccharides; Production; Proteins; Publishing; Regulation; Reporting; Research; Role; Salmonella; Salmonella enterica; Salmonella infections; Salmonella typhi; Salmonella typhimurium; Sepsis; Site; Structure; Surface; Systemic disease; Temperature; Therapeutic; Typhoid Fever; Urinary tract infection; Work; acute infection; antimicrobial; appendage; chemokine; chronic infection; comparative; cytokine; gastrointestinal; immune clearance; innovation; interest; mortality; mouse model; pathogen; tool; transcription factor; transmission process

PROJECT SUMMARY Salmonellae are Enterobacteriaceae that cause a spectrum of diseases in humans and animals, including enteric (typhoid) fever and gastroenteritis. Typhoid fever, caused primarily by Salmonella enterica serovar Typhi (S. Typhi), results in a life-threatening systemic disease that is responsible for significant morbidity and mortality annually worldwide. Approximately 5% of individuals infected with S. Typhi become chronic carriers with the gallbladder (GB) as the site of persistence. S. Typhi is a human- restricted pathogen, therefore asymptomatic carriers represent a critical reservoir for further spread of disease. We have demonstrated that gallstones (GSs) aid in the development and maintenance of GB carriage in a mouse model (utilizing S. Typhimurium, which causes a typhoid-fever like disease in mice) and in humans, serving as a substrate to which salmonellae attach and form a protective biofilm. Thus, biofilm formation is a key step in the establishment of carriers. Salmonella in biofilms are known to be recalcitrant to antibiotics and host immunity, presenting a challenge for traditional treatment methods. How S. Typhi subverts the initial immune response during biofilm development and establishes chronic infection is poorly understood. Immune escape likely involves extracellular matrix (ECM) components, but the responsible factors are not known. We focus this proposal on curli fibers/pili, surface appendages that are required for S. Typhimurium biofilm formation, mediate attachment and are sensed by pattern recognition receptors. While published reports suggest curli is not produced in S. Typhi, our preliminary data demonstrates that it is produced, but may be regulated differently than in S. Typhimurium. Furthermore, we demonstrate that curli gene expression is enhance ~30-fold in human bile (but not mouse or ox bile). We address our hypotheses by defining genes involved in curli gene expression, specifically those responding to human bile, the factors in human bile mediating gene activation, and the production of curli on GSs from the mouse model and from human carriers in Kenya. Determining the expression of curli during development of persistent infection in this understudied organ, and having the expertise, preliminary results and tools to examine it, will have a strong and sustained influence on the field and will identify key inflection points on which to focus future work.

项目总结

项目成果

The Effect of the Gallbladder Environment during Chronic Infection on Salmonella Persister Cell Formation.

• DOI: 10.3390/microorganisms10112276
• 发表时间: 2022-11-16
• 期刊: Microorganisms
• 影响因子: 4.5
• 作者: González JF;Hitt R;Laipply B;Gunn JS
• 通讯作者: Gunn JS

Salmonella Biofilms Tolerate Hydrogen Peroxide by a Combination of Extracellular Polymeric Substance Barrier Function and Catalase Enzymes.

• DOI: 10.3389/fcimb.2021.683081
• 发表时间: 2021
• 期刊: Frontiers in cellular and infection microbiology
• 影响因子: 5.7
• 作者: Hahn MM;González JF;Gunn JS
• 通讯作者: Gunn JS

Salmonella Biofilm Formation, Chronic Infection, and Immunity Within the Intestine and Hepatobiliary Tract.

• DOI: 10.3389/fcimb.2020.624622
• 发表时间: 2020
• 期刊: Frontiers in cellular and infection microbiology
• 影响因子: 5.7
• 作者: Harrell JE;Hahn MM;D'Souza SJ;Vasicek EM;Sandala JL;Gunn JS;McLachlan JB
• 通讯作者: McLachlan JB

Enhanced biofilm and extracellular matrix production by chronic carriage versus acute isolates of Salmonella Typhi.

• DOI: 10.1371/journal.ppat.1009209
• 发表时间: 2021-01
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Devaraj A;González JF;Eichar B;Thilliez G;Kingsley RA;Baker S;Allard MW;Bakaletz LO;Gunn JS;Goodman SD
• 通讯作者: Goodman SD

L-Arabinose Transport and Metabolism in Salmonella Influences Biofilm Formation.

• DOI: 10.3389/fcimb.2021.698146
• 发表时间: 2021
• 期刊: Frontiers in cellular and infection microbiology
• 影响因子: 5.7
• 作者: Vasicek EM;O'Neal L;Parsek MR;Fitch J;White P;Gunn JS
• 通讯作者: Gunn JS