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Lactic Acid Bacteria that Detect & Inhibit Enterococci in the Mammalian GI Tract

检测的乳酸菌

基本信息

批准号：
9272922
负责人：
GARY M DUNNY
金额：
$ 33.77万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2018-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9272922
关键词：
Address Animal Experiments Animal Model Animals Antibiotic Resistance Antibiotic Therapy Antibiotics Bacteria Bacteriophages Benchmarking Bile fluid Bioavailable Biological Metamorphosis Blood Circulation Cell Wall Cells Centers for Disease Control and Prevention (U.S.)Chlorides Cleaved cell Cloning Communicable Diseases Communication Detection Development Directed Molecular Evolution Disease Engineering Enterococcus Enterococcus faecalis Enterococcus faecium Environment Enzymes Feedback Future Gastrointestinal tract structure Gene Expression Genes Genetic Genetic Engineering Goals Health Care Costs Healthcare Systems Heart Hospitals Human Incidence Individual Infection Intervention Intestines Lactobacillus Lactococcus Lactococcus lactis Lead Length of Stay Liver Mammals Membrane Membrane Proteins Methods Modeling Modification Morbidity - disease rate Mus Nosocomial Infections Operon Oral Organism Pathogenicity Patients Peptide Hydrolases Peptides Peptidoglycan Pheromone Plasmids Probability Probiotics Production Protein Engineering Proteins Reporter Genes Reporting Resistance Resistance development Resort Severities Signal Transduction Skin Spleen Stomach Structure Surface Symbiosis System Technology Testing Therapeutic Vacuum Vancomycin Vancomycin resistant enterococcus Virulence Work antimicrobial antimicrobial peptide bile salts biophysical properties cost endolysin enterocin experimental study fighting gastrointestinal gut microbiota improved in vivo insight killings lactic acid bacteria mathematical model microbiota microorganism mortality multi-scale modeling pathogen peptide pheromone cCF10 promoter protein expression public health relevance response screening spatiotemporal therapeutic development

项目摘要

DESCRIPTION (provided by applicant): Enterococci are bacteria that grow naturally inside human intestines. Over the last few decades, these pathogens have developed resistance to our most potent antibiotics, including vancomycin, an antibiotic of last resort for infectious disease. Vancomycin-resistant Enterococcus (VRE) does not cause illness to healthy individuals. But it does cause severe illness to hospital patients, especially the ones who have undergone antibiotic therapy. Antibiotic therapy eliminates a lot of the "good" bacteria in the gut of humans. VRE grab and fill this vacuum, spreading quickly from the intestines to the bloodstream and from there to the spleen, the liver, the heart. There they grow and cause disease that can no longer be easily treated with antibiotics. We genetically engineer lactic acid bacteria (LAB) to specifically target enterococcus inside gastrointestinal (GI) tracts. We propose to administer these cellbots to mice and examine if enterococcus vanishes from mouse GI tracts. We pursue three specific aims: First we engineer "smart" LAB that can detect enterococci. Upon detection, engineered LAB produce and release proteins. In the second aim, we engineer these proteins to be lethal to enterococci. In the third aim, we will examine the efficacy of our modified LAB in mice. We will infect mice with enterococcus and then administer LAB to them. The main hypothesis is that engineered LAB kill enterococci and stop their colonization inside animal GI tracts. If successful, these experiments can lead to the development of a promising therapeutic strategy against enterococcal infections.

描述（由申请人提供）：肠球菌是在人类肠道内自然生长的细菌。在过去的几十年里，这些病原体已经对我们最有效的抗生素产生了耐药性，包括万古霉素，一种治疗传染病的最后手段抗生素。耐万古霉素肠球菌 (VRE) 不会对健康个体造成疾病。但它确实会给住院病人，尤其是接受抗生素治疗的病人带来严重的疾病。抗生素治疗消除了肠道中的大量“好”细菌人类的。 VRE 抓住并填补了这个真空，迅速从肠道扩散到血液，再从那里扩散到脾脏、肝脏和心脏。它们在那里生长并引起抗生素无法轻易治疗的疾病。我们通过基因工程改造乳酸细菌（LAB）专门针对胃肠道（GI）内的肠球菌。我们建议将这些细胞机器人注射到小鼠身上，并检查肠球菌是否从小鼠胃肠道中消失。我们追求三个具体目标：首先，我们设计可以检测肠球菌的“智能”实验室。一旦检测到，工程实验室就会产生并释放蛋白质。在第二个目标中，我们将这些蛋白质设计为对肠球菌具有致命性。在第三个目标中，我们将检查我们改良的 LAB 在小鼠中的功效。我们将用肠球菌感染小鼠，然后给它们注射 LAB。主要假设是工程乳酸菌杀死肠球菌并阻止其在动物胃肠道内定植。如果成功，这些实验可以开发出一种有前途的肠球菌感染治疗策略。

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Solving Stochastic Reaction Networks with Maximum Entropy Lagrange Multipliers.

DOI：
10.3390/e20090700
发表时间：
2018-09-12
期刊：
Entropy (Basel, Switzerland)
影响因子：
0
作者：
Vlysidis M;Kaznessis YN
通讯作者：
Kaznessis YN

pMPES: A Modular Peptide Expression System for the Delivery of Antimicrobial Peptides to the Site of Gastrointestinal Infections Using Probiotics.

DOI：
10.3390/ph9040060
发表时间：
2016-10-05
期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
0
作者：
Geldart K;Forkus B;McChesney E;McCue M;Kaznessis YN
通讯作者：
Kaznessis YN

On a theory of stability for nonlinear stochastic chemical reaction networks.

DOI：
10.1063/1.4919834
发表时间：
2015-05
期刊：
The Journal of chemical physics
影响因子：
0
作者：
P. Smadbeck;Y. Kaznessis
通讯作者：
P. Smadbeck;Y. Kaznessis

Antimicrobial Probiotics Reduce Salmonella enterica in Turkey Gastrointestinal Tracts.

DOI：
10.1038/srep40695
发表时间：
2017-01-17
期刊：
Scientific reports
影响因子：
4.6
作者：
Forkus B;Ritter S;Vlysidis M;Geldart K;Kaznessis YN
通讯作者：
Kaznessis YN

Structure-Function Analysis of the Two-Peptide Bacteriocin Plantaricin EF.

DOI：
10.1021/acs.biochem.6b00588
发表时间：
2016-09-13
期刊：
BIOCHEMISTRY
影响因子：
2.9
作者：
Ekblad, Bie;Kyriakou, Panagiota K.;Oppegard, Camilla;Nissen-Meyer, Jon;Kaznessis, Yiannis N.;Kristiansen, Per Eugen
通讯作者：
Kristiansen, Per Eugen