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Mechanism of A. actinomycetemcomitans Outer Membrane Vesicle Delivery to Target Cells

伴放线放线菌外膜囊泡递送至靶细胞的机制

基本信息

批准号：
9300913
负责人：
Angela C. Brown
金额：
$ 11.27万
依托单位：
LEHIGH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9300913
关键词：
Actinobacillus actinomycetemcomitans Affinity Antibiotics Area Bacteria Bacterial Infections Bacterial Toxins Binding Proteins Biological Assay Bulla Cell Communication Cells Charge Cholesterol Confocal Microscopy Development Digestion Electrostatics Encapsulated Endocarditis Etiology Future Gram-Negative Bacteria Host Defense Mechanism Immunoprecipitation Infection Infective endocarditis Integral Membrane Protein Juvenile Periodontitis Laboratories Lipids Lipopolysaccharides Location Measures Mediating Membrane Membrane Microdomains Methods Organism Outcome Pathogenicity Periodontal Infection Periodontitis Play Process Prokaryotic Cells Property Proteins Research Role Series Surface System Systemic disease Systemic infection Testing Tooth structure Toxic effect Toxin Training Trypsin Universities Vesicle Virulence Factors Work alternative treatment experimental study leukotoxin microbial community novel novel strategies pathogen prevent targeted treatment

项目摘要

Project Summary The Gram negative pathogen, Aggregatibacter actinomycetemcomitans, is the etiologic agent of localized aggressive periodontitis (LAP) and other systemic infections, including infective endocarditis. Like other pathogenic Gram negative organisms, A. actinomycetemcomitans produces outer membrane vesicles (OMVs), which encapsulate virulence factors for delivery to target cells. A. actinomycetemcomitans OMVs are enriched in a leukotoxin (LtxA), and strains that produce more LtxA also secrete more OMVs, indicating that LtxA may play a role in the delivery of the OMVs to the host cell. The specific role of LtxA in this process has not yet been fully demonstrated. To accomplish this, the PI intends to systematically study the lipid and protein components of both the OMV and the target cell required for delivery of the OMV to the target cell. The research will answer vital questions about the pathogenicity of A. actinomycetemcomitans, and result in the identification of specific factors that could be targeted for the treatment of infection. In our future work, we will develop molecules to target these factors for the development of antibiotic alternative treatments. In addition, we will investigate the delivery of OMVs to other bacterial cells, to understand their role in cell-to-cell communication.

项目概要革兰氏阴性病原体，Aggregatibacter actinomycetemcomitans，是局部感染的病原体侵袭性牙周炎（LAP）和其他全身感染，包括感染性心内膜炎。和其他人一样致病性革兰氏阴性生物体，A. actinomycetemcomitans 产生外膜囊泡 (OMV)，其封装毒力因子以递送至靶细胞。 A. actinomycetemcomitans OMV 富含白细胞毒素 (LtxA)，并且产生更多 LtxA 的菌株也分泌更多的 OMV，表明 LtxA 可能在将 OMV 递送至宿主细胞的过程中发挥作用。具体的 LtxA 在此过程中的作用尚未得到充分证明。为了实现这一目标，PI 打算系统地研究 OMV 和递送所需的靶细胞的脂质和蛋白质成分 OMV 至靶细胞。该研究将回答有关 A. actinomycetemcomitans 致病性的重要问题，并得出确定可用于治疗感染的特定因素。在今后的工作中，我们将开发针对这些因素的分子，以开发抗生素替代疗法。此外，我们将研究 OMV 向其他细菌细胞的传递，以了解它们在细胞间的作用沟通。