Is DNA uptake the Achilles Heel of N. gonorrhoeae?

项目摘要 我们最近发现，奈瑟氏球菌通过一种基于遗传的新机制杀死Ngo， 能力和DNA甲基化状态。与这些体外研究结果相一致，人的大肠杆菌N.长形花 加速Ngo从小鼠中的清除，而Ngo DNA摄取突变体抵抗这种清除。我们提出了一个 奈瑟菌DNA如何杀死Ngo的模型。基于这些和其他发现，我们假设任何DNA 具有杀死Ngo的潜力，只要它被吸收到细胞中，并且其甲基化模式被认为是外来的。 病原体在这个R21中，我们提出了这个想法，使用体外方法和小鼠模型降低Ngo 生殖道感染这些研究使我们能够评估DNA作为替代性淋球菌杀微生物剂的潜力 揭示了细菌奈瑟菌-致病性奈瑟菌相互作用的一个鲜为人知的方面。

Project Summary We recently discovered that commensal Neisseria kill Ngo through a novel mechanism that is based on genetic competence and DNA methylation state. Consistent with these in vitro findings, human commensal N. elongata (Nel) accelerates Ngo clearance from the mouse, and an Ngo DNA uptake mutant resists this clearance. We propose a model for how commensal Neisseria DNA kills Ngo. Based on these and other findings, we hypothesize that any DNA has the potential to kill Ngo, provided it is taken up into the cell and its methylation pattern is considered foreign to the pathogen. In this R21, we propose to this idea using in vitro approaches and the mouse model of Ngo lower genital tract infection. These studies allow us to assess the potential of DNA as an alternative gonococcal microbicide and shed light on a little understood facet of commensal Neisseria-pathogenic Neisseria interactions.