Tzeng Yih-Ling, Stephens David S
Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA; Laboratories of Microbial Pathogenesis, Medical Research Service, Veterans Affairs Medical Center, Decatur, GA 30033, USA.
Biochim Biophys Acta. 2015 Nov;1848(11 Pt B):3026-31. doi: 10.1016/j.bbamem.2015.05.006. Epub 2015 May 19.
Antimicrobial peptides (AMPs) play an important role as a host defense against microbial pathogens and are key components of the human innate immune response. Neisseria meningitidis frequently colonizes the human nasopharynx as a commensal but also is a worldwide cause of epidemic meningitis and rapidly fatal sepsis. In the human respiratory tract, the only known reservoir of N. meningitidis, meningococci are exposed to human endogenous AMPs. Thus, it is not surprising that meningococci have evolved effective mechanisms to confer intrinsic and high levels of resistance to the action of AMPs. This article reviews the current knowledge about AMP resistance mechanisms employed by N. meningitidis. Two major resistance mechanisms employed by meningococci are the constitutive modification of the lipid A head groups of lipooligosaccharides by phosphoethanolamine and the active efflux pump mediated excretion of AMPs. Other factors influencing AMP resistance, such as the major porin PorB, the pilin biogenesis apparatus, and capsular polysaccharides, have also been identified. Even with an inherently high intrinsic resistance, several AMP resistance determinants can be further induced upon exposure to AMPs. Many well-characterized AMP resistance mechanisms in other Gram-negative bacteria are not found in meningococci. Thus, N. meningitidis utilizes a limited but highly effective set of molecular mechanisms to mediate antimicrobial peptide resistance. This article is part of a Special Issue entitled: Bacterial Resistance to Antimicrobial Peptides.
抗菌肽(AMPs)作为宿主抵御微生物病原体的防御机制发挥着重要作用,是人类固有免疫反应的关键组成部分。脑膜炎奈瑟菌常作为共生菌定殖于人类鼻咽部,但也是全球流行性脑膜炎和迅速致命性败血症的病因。在人类呼吸道这一已知的脑膜炎奈瑟菌唯一储存库中,脑膜炎球菌会接触到人类内源性抗菌肽。因此,脑膜炎球菌进化出有效机制以赋予其对抗菌肽作用的固有且高水平抗性也就不足为奇了。本文综述了目前关于脑膜炎奈瑟菌所采用的抗菌肽抗性机制方面的知识。脑膜炎球菌采用的两种主要抗性机制是通过磷酸乙醇胺对脂寡糖的脂质A头部基团进行组成性修饰以及通过主动外排泵介导抗菌肽的排泄。其他影响抗菌肽抗性的因素,如主要孔蛋白PorB、菌毛生物合成装置和荚膜多糖,也已被确定。即使具有固有的高内在抗性,在接触抗菌肽后,几种抗菌肽抗性决定因素仍可进一步被诱导。在其他革兰氏阴性菌中许多已被充分表征的抗菌肽抗性机制在脑膜炎球菌中并未发现。因此,脑膜炎奈瑟菌利用一套有限但高效的分子机制来介导对抗菌肽的抗性。本文是名为“细菌对抗菌肽的抗性”的特刊一部分。