Revisiting alginate paradigms

重新审视藻酸盐范式

基本信息

批准号：
10294953
负责人：
Daniel J Wozniak
金额：
$ 48.81万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-11-03 至 2023-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10294953
关键词：
Alginates Antimicrobial Resistance Bacteria Biochemical Biochemical Genetics Biology Cells Chronic Chronic lung disease Clinical Communities Cystic Fibrosis Data Disease Equilibrium Genetic Diseases Goals Hypersensitivity Immune response Immunologics Intervention Knowledge Lung infections Maintenance Mediating Microbial Biofilms Molecular Monitor Mutation Pathogenesis Patients Persons Phenotype Polysaccharides Population Prevalence Production Property Proteins Pseudomonas aeruginosa Pulmonary Cystic Fibrosis Reactive Oxygen Species Research Respiratory Tract Infections Role Structure Testing Translating Variant Virulence antimicrobial antimicrobial drug chronic infection clinical prognosis cost cystic fibrosis airway cystic fibrosis patients effective therapy experimental study fitness genetic approach high risk immunopathology in vivo infection risk inflammatory milieu member microbial community microbiota mucoid novel therapeutics opportunistic pathogen patient population trait

项目摘要

Project Abstract This application seeks to define the molecular mechanisms and fitness benefits of alginate overproduction by mucoid variants of Pseudomonas aeruginosa. Specifically we will define features of the alginate biofilm matrix that enhance P. aeruginosa persistence and better understand the role of alginate in maintaining passive protection to the P. aeruginosa microbial community in the CF airway. This proposal will use state-of-the art molecular, biochemical, immunological, and genetic approaches to probe aspects of alginate pathogenesis and to reevaluate some long-standing paradigms. To date, the mechanisms underlying biofilm formation by alginate producing bacteria is not well understood. Aim 1 will investigate the biochemical and genetic basis for alginate biofilm matrix maintenance of biofilm integrity, structure, and antimicrobial resistance properties. While it is clear that mucoid variants predominate during chronic airway infection in CF patients, rarely are they present as pure clonal mucoid isolates. Instead, mucoid bacteria are typically associated with mixed populations of wild type P. aeruginosa that have not undergone mucoid conversion, as well as spontaneous suppressors that arise. The goal of Aim 2 is to test the hypothesis that this mixed consortia confers fitness benefits to the P. aeruginosa community as a whole that is not observed in either nonmucoid or mucoid bacteria alone. Alginate expression in the CF lung correlates with a poor clinical prognosis. However there are gaps in our knowledge regarding specific properties that alginate overproduction affords bacteria and the microbial consortia within the airway. The completion of these aims will lead to a deeper understanding of alginate biology and translate into novel therapies or interventions for CF patients colonized with mucoid P. aeruginosa.

项目摘要该应用旨在定义藻酸盐过度生产的分子机制和适应性益处铜绿假单胞菌的粘液变体。具体而言，我们将定义藻酸盐生物膜基质的特征这可以增强铜绿假单胞菌的持久性，并更好地理解藻酸盐在维持被动的作用保护CF气道的铜绿假单胞菌微生物群落。该提案将使用最先进的分子，生化，免疫和遗传方法来探测藻酸盐发病机理的各个方面，并重新评估一些长期的范式。迄今为止，机制尚不清楚通过藻酸盐产生细菌形成潜在的生物膜。 AIM 1将调查生物膜完整性，结构和生物膜基质维持藻酸盐生物膜基质的生化和遗传基础抗菌抗性特性。虽然很明显，在慢性气道期间，粘液变体占主导地位 CF患者的感染，很少以纯克隆粘液分离株的形式出现。相反，粘液细菌是通常与尚未经历过粘液的野生型P.铜绿假单胞菌的混合种群有关转换以及出现的自发抑制器。目标2的目的是检验以下假设混合财团赋予了整个铜绿假单胞菌社区的健身益处单独的非糖类或粘液细菌。 CF肺中藻酸盐表达与临床不良相关预后。但是，我们关于藻酸盐的特定属性的知识中存在差距生产过多可为气道内的细菌和微生物财团提供。这些目标的完成将导致对藻酸盐生物学的深入了解，并转化为CF的新疗法或干预措施用粘液孢子虫定殖的患者。

项目成果

期刊论文数量（38）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Dioxane-Linked Novel Bacterial Topoisomerase Inhibitors Exhibit Bactericidal Activity against Planktonic and Biofilm Staphylococcus aureus In Vitro.

DOI：
10.1128/spectrum.02056-22
发表时间：
2022-12-21
期刊：
MICROBIOLOGY SPECTRUM
影响因子：
3.7
作者：
Chen, Anna;Dellos-Nolan, Sheri;Lu, Yanran;West, Jason S.;Wozniak, Daniel J.;Mitton-Fry, Mark J.
通讯作者：
Mitton-Fry, Mark J.

Mannose Conjugated Polymer Targeting P. aeruginosa Biofilms.

DOI：
10.1021/acsinfecdis.0c00407
发表时间：
2020-11-13
期刊：
ACS infectious diseases
影响因子：
5.3
作者：
Limqueco E;Passos Da Silva D;Reichhardt C;Su FY;Das D;Chen J;Srinivasan S;Convertine A;Skerrett SJ;Parsek MR;Stayton PS;Ratner DM
通讯作者：
Ratner DM

CdrA Interactions within the Pseudomonas aeruginosa Biofilm Matrix Safeguard It from Proteolysis and Promote Cellular Packing.