Anti-staphylococcal activities of A. actinomycetemcomitans dispersin B

伴放线放线菌分散素 B 的抗葡萄球菌活性

基本信息

批准号：
7897845
负责人：
JEFFREY B KAPLAN
金额：
$ 19.36万
依托单位：
UNIV OF MED/DENT OF NJ-NJ DENTAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-22 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7897845
关键词：
Acetylglucosamine Actinobacillus actinomycetemcomitans Acute Adhesions Anti-Infective Agents Antibiotic Resistance Antibiotics Area Bacteremia Bacteria Biocide Biocompatible Materials Biological Assay Catheters Cells Cessation of life Community Hospitals Daptomycin Devices Enzymes Evolution Exhibits Extracellular Matrix Fluorescence Microscopy Gentamicins Genus staphylococcus Goals Growth Human Implant In Vitro Infection Infection prevention Knowledge Laboratories Lead Measures Mediating Medical Device Methods Microbial Biofilms Minocycline Modeling Morphology Names Outcome Play Polymers Polysaccharides Polyurethanes Prevention Research Resistance Resistance development Rifampin Risk Role Sepsis Simulate Solutions Staphylococcus aureus Staphylococcus epidermidis Surface Testing Vancomycin abstracting antimicrobial antimicrobial drug bacterial resistance base cohesion immune resistance in vivo inhibitor/antagonist innovation killings novel pathogen prevent quorum sensing resistant strain tigecycline usnic acid

项目摘要

The Project Summary/Abstract was modified to reflect the changes described above: A major risk associated with implanted medical devices is their high rate of infection. Bacteria that colonize medical devices form matrix-encased biofilms that resist antimicrobial therapy and are often difficult or impossible to eradicate. The extracellular matrix of Staphylococcus aureus and Staphylococcus epidermidis, the most common device-associated pathogens, contains a sticky polysaccharide named PNAG (poly-N-acetylglucosamine) that mediates surface attachment, intercellular adhesion, biocide resistance and immune evasion. Our laboratory discovered an enzyme (dispersin B) that degrades PNAG. Preliminary studies indicate that dispersin B inhibits staphylococcal biofilm formation, detaches pre-formed staphylococcal biofilms, and sensitizes staphylococcal biofilm cells to antimicrobial killing in vitro. Our hypothesis is that dispersin B will be a clinically useful anti-biofilm agent for the treatment and prevention of staphylococcal biofilm infections in vivo. The goal of the present proposal is to demonstrate that dispersin B acts synergistically with antibiotics to detach and kill S. aureus and S. epidermidis biofilms in vitro. Dispersin B will be tested both in solution in a simulated daily antibiotic catheter lock assay, and loaded onto polyurethane disks, either alone or in combination with antibiotics, in a model for antiinfective device coatings. The antibiotics that we plan to test include tigecycline and vancomycin. The results of the proposed studies will extend our knowledge about the mechanism of PNAGmediated biofilm resistance to specific antibiotics, and will demonstrate the feasibility of using dispersin B as anti-biofilm agent in vivo. Since dispersin B does not kill bacteria or inhibit their growth, dispersin B-based strategies may be less prone to the evolution of resistance than strategies utilizing conventional antibiotics.

修改了项目摘要/摘要以反映上述变化：与植入医疗设备相关的主要风险是它们的高感染率。定殖的医疗器械的细菌形成基于基质的生物膜，可抵抗抗菌治疗，通常难以或不可能消除。葡萄球菌金黄色葡萄球菌和表皮葡萄球菌的细胞外基质是最常见的设备相关病原体，含有一种粘性多糖，称为PNAG（Poly-N-乙酰葡萄糖），可介导表面附着，层间粘附，生物胶质，免疫耐药和免疫效果。我们的实验室发现了一种降解PNAG的酶（分散b）。初步研究表明，散布B会抑制葡萄球菌生物膜的形成，脱离预成型的葡萄球菌生物膜，并使葡萄球菌生物膜细胞敏感对抗菌素杀死抗菌素。我们的假设是，分散B将是一种用于治疗和预防体内葡萄球菌生物膜感染的临床上有用的抗生物胶片剂。本提案的目的是证明分散与抗生素协同作用以脱离并杀死金黄色葡萄球菌和表皮链球菌生物膜。在模拟的每日抗生素导管锁定测定中，将在溶液中进行分散，并在抗侵染装置涂料的模型中，将其装入单独或与抗生素混合到聚氨酯盘上。我们计划测试的抗生素包括Tigecycline和Vanomycin。拟议的研究的结果将扩展我们对特定抗生素抗生物膜抗性的机理的了解，并将证明在体内使用分散剂作为抗生物膜剂的可行性。由于散布在B不会杀死细菌或抑制其生长，因此基于B的策略可能比使用常规抗生素的策略不容易发生抵抗的发展。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Characterization of TEM-1 β-Lactamase-Producing Kingella kingae Clinical Isolates.

TEM-1 β-内酰胺酶生产 Kingella kingae 临床分离株的表征。

DOI：
10.1128/aac.00318-13
发表时间：
2013
期刊：
Antimicrobial agents and chemotherapy
影响因子：
4.9
作者：
Banerjee,Anushree;Kaplan,JeffreyB;Soherwardy,Amenah;Nudell,Yoav;Mackenzie,GraceA;Johnson,Shannon;Balashova,NataliyaV
通讯作者：
Balashova,NataliyaV

Recombinant human DNase I decreases biofilm and increases antimicrobial susceptibility in staphylococci.