Surface Proteins of Bacillus anthracis

炭疽杆菌表面蛋白

基本信息

批准号：
10682088
负责人：
Dominique M. Missiakas
金额：
$ 40.13万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-01-01 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10682088
关键词：
Adhesions Affect Alveolar Macrophages Animals Anthrax disease Anti-Bacterial Agents Attenuated Vaccines Bacillus Bacillus anthracis Bacillus anthracis spore Bacillus cereus Bacteria Bacterial Adhesins Binding Biochemical Candidate Disease Gene Carbohydrates Cavia Cell Communication Cell Cycle Cell Wall Cell membrane Cells Collection Communicable Diseases Complex Consumption Cultured Cells Cutaneous Data Dendritic Cells Disease Edema Enabling Factors Environment Enzymes Epithelium Food Contamination Gastrointestinal tract structure Genes Germination Goals Gram-Positive Bacteria Growth Host Defense Human Hydrolase Immunocompetent Infection Infectious Diseases Research Ingestion Inhalation Insecta Integrins Intercellular Junctions Intestinal Mucosa Intestines Invaded Kinetics Length Libraries Life Style Ligation Link Lung Lymphatic System Lymphoid Tissue M cell Mammals Mediating Membrane Proteins Modeling Molecular Mucins Mus Mutation Organism Organoids Pathogenesis Pathway interactions Penetration Peptidoglycan Pharmaceutical Preparations Physically Challenged Plasmids Polymerase Polymers Polysaccharides Process Proteins Reproduction spores Research Resistance Route Shapes Site Structure Surface Testing Thick Transferase Virulence Virulent Viscosity base bioweapon cell growth gastrointestinal gastrointestinal infection glycosyltransferase guinea pig model intestinal epithelium knockout animal lethal factor member monocyte monolayer mucinase mutant novel pathogen respiratory transcytosis uptake

项目摘要

ABSTRACT Bacillus anthracis, the anthrax agent, is a member of the Bacillus cereus sensu lato group, which includes invasive pathogens of mammals or insects as well as nonpathogenic environmental strains. Clade 1 members of the B. cereus s.l. group can exchange virulence-plasmids via horizontal transfer with B. anthracis to cause anthrax-like disease too. The natural route of infection is ingestion, often by grazing animals or, in humans, by the consumption of spore-contaminated food (gastrointestinal, GI anthrax). The proposal aims to determine the mechanisms of B. anthracis spore invasion across intestinal epithelia. The central hypothesis is that spores of B. anthracis and anthrax-causing strains germinate in the intestinal tract of infected animals. Our working model postulates that vegetative bacilli secrete several enzymes with mucin-binding and mucin-degrading activities to penetrate the thick mucin layer. Next, the adhesins BslA and BslB mediate uptake of B. anthracis into intestinal cells. BslA and BslB are two of 22 S-layer associated proteins (BSLs) that form the surface (S)- protein layer. BSLs associate via S-layer homology (SLH)-domains with secondary cell wall polysaccharide (SCWP), a peptidoglycan linked carbohydrate polymer. The integrity of the S-layer and SCWP is important for the activity of BSLs. Further, the bslA gene is located on the mobilizable pXO1 virulence plasmid. Thus, we propose that surface-protein layers contribute broadly to the pathogenesis of anthrax-causing organisms. Here, we will use mice and intestinal organoids to model GI anthrax and test our predictions. We propose to study the pathway for the synthesis of SCWP that is required to display the surface-protein layer and is essential for growth. We expect that the elucidation of the assembly pathway of SCWP will serve as a paradigm for the study of other complex polymers of Gram-positive bacteria and reveal new targets of antibacterial drugs. We anticipate that unravelling intestinal mucosa interactions with anthrax and anthrax-like pathogens will collectively advance the field of infectious diseases research.

抽象的炭疽芽孢杆菌，炭疽剂，是Cereus cereus sensu Lato组的成员，其中包括哺乳动物或昆虫的侵入性病原体以及非致病性环境菌株。进化枝1成员 B. cereus S.L.小组可以通过水平转移与炭疽芽孢杆菌交换毒力质数，以引起也类似炭疽病的疾病。自然感染的途径是摄入，通常是通过放牧动物或在人类中，消费孢子污染的食物（胃肠道，胃肠道）。该提议旨在确定跨肠道上皮的炭疽芽孢杆菌孢子侵袭的机制。中心假设是孢子炭疽芽孢杆菌和引起炭疽病的菌株在感染动物的肠道中发芽。我们的工作模型假设植物性杆菌分泌几种酶，并粘合粘蛋白降解穿透浓稠的粘蛋白层的活动。接下来，粘合剂BSLA和BSLB介导了炭疽芽孢杆菌的摄取进入肠细胞。 BSLA和BSLB是22个S层相关蛋白（BSL）中的两个，它们形成了表面 - 蛋白质层。 BSLS通过S层同源性（SLH） - 具有次级细胞壁多糖的域（SCWP），一种肽聚糖连接的碳水化合物聚合物。 S层和SCWP的完整性对于 BSL的活性。此外，BSLA基因位于可动动的PXO1毒力质粒上。因此，我们提出表面蛋白质层对引起炭疽病的生物的发病机理广泛贡献。这里，我们将使用小鼠和肠道器官来对胃肠道进行建模并测试我们的预测。我们建议学习 SCWP合成的途径是显示表面蛋白质层所需的，对于生长。我们预计SCWP的组装途径的阐明将作为研究革兰氏阳性细菌的其他复杂聚合物，并揭示了抗菌药物的新靶标。我们预计肠道粘膜与炭疽和类似炭疽的病原体的相互作用将共同推进了传染病研究领域。

项目成果

期刊论文数量（28）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Bacillus anthracis secretes proteins that mediate heme acquisition from hemoglobin.

DOI：
10.1371/journal.ppat.1000132
发表时间：
2008-08-22
期刊：
PLOS PATHOGENS
影响因子：
6.7
作者：
Maresso, Anthony W.;Garufi, Gabriella;Schneewind, Olaf
通讯作者：
Schneewind, Olaf

GneZ, a UDP-GlcNAc 2-epimerase, is required for S-layer assembly and vegetative growth of Bacillus anthracis.

GneZ 是一种 UDP-GlcNAc 2-差向异构酶，是炭疽杆菌 S 层组装和营养生长所必需的。

DOI：
10.1128/jb.01829-14
发表时间：
2014
期刊：
Journal of bacteriology
影响因子：
3.2
作者：
Wang,Ya-Ting;Missiakas,Dominique;Schneewind,Olaf
通讯作者：
Schneewind,Olaf

Bacillus anthracis lcp Genes Support Vegetative Growth, Envelope Assembly, and Spore Formation.

炭疽芽孢杆菌 lcp 基因支持营养生长、包膜组装和孢子形成。

DOI：
10.1128/jb.00656-15
发表时间：
2015
期刊：
Journal of bacteriology
影响因子：
3.2
作者：
LiszewskiZilla,Megan;Lunderberg,JMark;Schneewind,Olaf;Missiakas,Dominique
通讯作者：
Missiakas,Dominique

Extraction and Purification of Wall-Bound Polymers of Gram-Positive Bacteria.

革兰氏阳性细菌的壁结合聚合物的提取和纯化。

DOI：
10.1007/978-1-4939-9154-9_5
发表时间：
2019
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
0
作者：
Chateau,Alice;Schneewind,Olaf;Missiakas,Dominique
通讯作者：
Missiakas,Dominique

Vaccine protection against Bacillus cereus-mediated respiratory anthrax-like disease in mice.

疫苗可预防小鼠蜡状芽孢杆菌介导的呼吸道炭疽样疾病。

DOI：
10.1128/iai.01346-12
发表时间：
2013
期刊：
Infection and immunity
影响因子：
3.1
作者：
Oh,So-Young;Maier,Hannah;Schroeder,Jay;Richter,GStefan;Elli,Derek;Musser,JamesM;Quenee,LaurianeE;Missiakas,DominiqueM;Schneewind,Olaf
通讯作者：
Schneewind,Olaf