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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通过以下方式定义藻酸盐过量生产的分子机制和健康益处：铜绿假单胞菌的粘液变种。具体来说，我们将定义藻酸盐生物膜基质的特征增强铜绿假单胞菌的持久性并更好地了解藻酸盐在维持被动性方面的作用对 CF 气道中铜绿假单胞菌微生物群落的保护。该提案将使用最先进的分子、生化、免疫学和遗传学方法来探索藻酸盐发病机制的各个方面并重新评估一些长期存在的范式。迄今为止，机制产生藻酸盐的细菌形成的潜在生物膜尚不清楚。目标 1 将调查海藻酸盐生物膜基质维持生物膜完整性、结构和生物化学和遗传基础抗微生物特性。虽然很明显粘液变体在慢性气道中占主导地位 CF 患者感染后，很少会以纯克隆粘液分离物的形式出现。相反，粘液细菌是通常与未经过粘液处理的野生型铜绿假单胞菌混合种群相关转换，以及出现的自发抑制。目标 2 的目标是检验以下假设：混合菌群为整个铜绿假单胞菌群落带来了适应性益处，而这在单独的非粘液或粘液细菌。 CF 肺中的藻酸盐表达与较差的临床表现相关预后。然而，我们对海藻酸盐的具体特性的了解还存在空白。过度生产会在呼吸道内产生细菌和微生物群落。这些目标的完成将导致对藻酸盐生物学的更深入了解，并转化为 CF 的新疗法或干预措施定植有粘液铜绿假单胞菌的患者。

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.