Handing Jonathan W, Ragland Stephanie A, Bharathan Urmila V, Criss Alison K
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, United States.
Front Microbiol. 2018 Nov 20;9:2688. doi: 10.3389/fmicb.2018.02688. eCollection 2018.
The mucosal inflammatory response to (Gc) is characterized by recruitment of neutrophils to the site of infection. Gc survives exposure to neutrophils by limiting the ability of neutrophils to make antimicrobial products and by expressing factors that defend against these products. The multiple transferable resistance (Mtr) system is a tripartite efflux pump, comprised of the inner membrane MtrD, the periplasmic attachment protein MtrC, and the outer membrane channel MtrE. Gc MtrCDE exports a diverse array of substrates, including certain detergents, dyes, antibiotics, and host-derived antimicrobial peptides. Here we report that MtrCDE contributes to the survival of Gc after exposure to adherent, chemokine-treated primary human neutrophils, specifically in the extracellular milieu. MtrCDE enhanced survival of Gc in neutrophil extracellular traps and in the supernatant from neutrophils that had undergone degranulation (granule exocytosis), a process that releases antimicrobial proteins into the extracellular milieu. The extent of degranulation was unaltered in neutrophils exposed to parental or mutant Gc. MtrCDE expression contributed to Gc defense against some neutrophil-derived antimicrobial peptides but not others. These findings demonstrate that the Mtr system contributes to Gc survival after neutrophil challenge, a key feature of the host immune response to acute gonorrhea.
对淋病奈瑟菌（Gc）的黏膜炎症反应的特征是中性粒细胞募集到感染部位。Gc通过限制中性粒细胞产生抗菌产物的能力以及表达抵御这些产物的因子，在暴露于中性粒细胞的情况下存活下来。多重可转移耐药（Mtr）系统是一种三方外排泵，由内膜MtrD、周质附着蛋白MtrC和外膜通道MtrE组成。Gc的MtrCDE能输出多种底物，包括某些去污剂、染料、抗生素和宿主来源的抗菌肽。在此我们报告，MtrCDE有助于Gc在暴露于贴壁的、经趋化因子处理的原代人中性粒细胞后存活，特别是在细胞外环境中。MtrCDE增强了Gc在中性粒细胞胞外陷阱和已发生脱颗粒（颗粒胞吐）的中性粒细胞上清液中的存活能力，脱颗粒过程会将抗菌蛋白释放到细胞外环境中。暴露于亲本或突变型Gc的中性粒细胞的脱颗粒程度未改变。MtrCDE的表达有助于Gc抵御一些中性粒细胞来源的抗菌肽，但对其他抗菌肽则无作用。这些发现表明，Mtr系统有助于Gc在中性粒细胞攻击后存活，这是宿主对急性淋病免疫反应的一个关键特征。
