Department of Immunobiology and the BIO5 Institute, University of Arizona, Tucson, AZ 85721, USA.
Department of Biology, Spelman College, Atlanta, GA 30314, USA.
Cell Host Microbe. 2019 Aug 14;26(2):228-239.e8. doi: 10.1016/j.chom.2019.07.003. Epub 2019 Aug 1.
The mucosa is colonized with commensal Neisseria. Some of these niches are sites of infection for the STD pathogen Neisseria gonorrhoeae (Ngo). Given the antagonistic behavior of commensal bacteria toward their pathogenic relatives, we hypothesized that commensal Neisseria may negatively affect Ngo colonization. Here, we report that commensal species of Neisseria kill Ngo through a mechanism based on genetic competence and DNA methylation state. Specifically, commensal-triggered killing occurs when the pathogen takes up commensal DNA containing a methylation pattern that it does not recognize. Indeed, any DNA will kill Ngo if it can enter the cell, is differentially methylated, and has homology to the pathogen genome. Consistent with these findings, commensal Neisseria elongata accelerates Ngo clearance from the mouse in a DNA-uptake-dependent manner. Collectively, we propose that commensal Neisseria antagonizes Ngo infection through a DNA-mediated mechanism and that DNA is a potential microbicide against this highly drug-resistant pathogen.
黏膜定植有共生奈瑟菌。其中一些小生境是性传播疾病病原体淋病奈瑟菌（Ngo）感染的部位。鉴于共生细菌对其病原相关细菌的拮抗行为，我们假设共生奈瑟菌可能会对 Ngo 定植产生负面影响。在这里，我们报告说，共生奈瑟菌通过基于遗传能力和 DNA 甲基化状态的机制杀死 Ngo。具体来说，当病原体摄取含有它不识别的甲基化模式的共生 DNA 时，就会发生共生触发的杀伤。事实上，如果任何 DNA 能够进入细胞、存在差异甲基化且与病原体基因组具有同源性，它就能杀死 Ngo。与这些发现一致的是，共生奈瑟菌伸长亚种以依赖于 DNA 摄取的方式加速 Ngo 从小鼠体内清除。总的来说，我们提出共生奈瑟菌通过 DNA 介导的机制拮抗 Ngo 感染，并且 DNA 是针对这种高度耐药病原体的潜在杀菌剂。
