Adaptive alterations of lipids in mitis group streptococci

摘要 作为细胞被膜的主要成分，脂质在细菌病原体的生存中起着无数的作用。 病原体可以调整其膜脂的生化特性（如静电荷），以科普 适应环境的变化和挑战。我们研究了缓症组链球菌中的脂质， 具体地，缓症链球菌、S. oralis和S. pneumoniae，它们具有非常接近的系统发育 关系S. mitis和S.口腔病原体是引起菌血症的主要原因之一 （血流感染）和感染性心内膜炎（心脏瓣膜感染）。S.肺炎是一种主要的人类 导致大多数儿童社区获得性肺炎和脑膜炎病例的病原体， 这是世界范围内儿童死亡的主要原因。尽管这些临床意义 生物和关键功能的脂质在宿主微生物的相互作用，膜生物学的mitis 链球菌组的研究不足，了解甚少。使用液相色谱/质谱法 (LC/MS）为基础的脂质组学，我们分析了轻症组链球菌细胞包膜中的脂质，并鉴定了 我们提出的几种新的表面性质对于应对抗生素、抗微生物 肽和宿主体内的不利条件。这个项目的首要假设是， 缓和组链球菌急剧改变其细胞包膜的带电脂质组成， 与宿主的相互作用以及它们对抗菌素应激的反应。我们建议分析结构， 缓症链球菌中阴离子脂质（Aim 1）和两性离子脂质（Aim 2）的生物合成及其在宿主中的作用 病原体相互作用（目标3）。所获得的知识将有助于更好地了解生存和 这些病原体在宿主中的毒力，并可能有助于开发新的治疗方法来对抗 抗生素耐药性

Abstract As major components of the cellular envelope, lipids play myriad roles in the survival of bacterial pathogens. Pathogens can adjust the biochemical properties (such as electrostatic charge) of their membrane lipids to cope with the changing and challenging conditions of their surroundings. We study lipids in the mitis group streptococci, specifically, Streptococcus mitis, S. oralis, and S. pneumoniae, which share a very close phylogenetic relationship. S. mitis and S. oralis are opportunistic pathogens that are among the leading causes of bacteremia (bloodstream infection) and infective endocarditis (heart valve infection). S. pneumoniae is a major human pathogen responsible for most cases of community-acquired pneumonia and meningitis in children and the elderly, and is a major cause of childhood mortality worldwide. Despite the clinical significance of these organisms and the critical functions of the lipids in host-microbe interactions, the membrane biology of mitis group streptococci is understudied and poorly understood. Using liquid chromatography/mass spectrometry (LC/MS)-based lipidomics, we analyzed lipids in the cell envelopes of mitis group streptococci and identified several novel surface properties which we propose are important for coping with antibiotics, antimicrobial peptides, and unfavorable conditions inside hosts. The overarching hypothesis of this project is that the ability of mitis group streptococci to drastically alter the charged lipid compositions of their cellular envelope impacts their interactions with hosts and their responses to antimicrobial stress. We propose to analyze the structure and biosynthesis of anionic (Aim 1) and zwitterionic lipids (Aim 2) in mitis group streptococci, and their roles in host- pathogen interactions (Aim 3). The knowledge gained will lead to a better understanding of the survival and virulence of these pathogens in the host and may facilitate the development of novel therapeutics to combat antibiotic resistance.