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

项目摘要 革兰氏阴性杆菌Aggregatibacter放线菌伴生菌是局限性肺炎的病原体 侵袭性牙周炎(LAP)和其他全身感染，包括感染性心内膜炎。像其他人一样 致病的革兰氏阴性菌，伴生放线菌产生外膜小泡(OMV)， 它封装了毒力因子，并将其输送到靶细胞。 放线菌伴生的OMV富含一种白毒素(Ltd XA)，而产生更多Ltd xA的菌株也 分泌更多的OMV，表明LtxA可能在将OMV运送到宿主细胞中发挥作用。具体的 Ltd.A在这一过程中的作用尚未得到充分展示。为了实现这一点，PI打算 系统研究OMV和靶细胞传递所需的脂肪和蛋白质成分 将OMV复制到目标单元。 这项研究将回答有关伴生放线菌致病性的关键问题，并导致 确定可作为治疗感染的目标的特定因素。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。

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.