Adaptive alterations of lipids in mitis group streptococci

轻症链球菌脂质的适应性改变

• 批准号: 10268226
• 负责人: Ziqiang Guan
• 金额: $ 47.47万
• 依托单位: UNIVERSITY OF TEXAS DALLAS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-23 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10268226
• 关键词: Acyltransferase; Anabolism; Antibiotic Resistance; Antibiotics; Antimicrobial Resistance; Bacteremia; Bacteria; Biochemical; Cardiolipins; Cations; Charge; Child; Childhood; Choline; Culture Media; Daptomycin; Detection; Development; Elderly; Electrostatics; Excision; Genes; Genetic; Glycerol; Gram-Positive Bacteria; Growth; Head; Heart Valves; Housekeeping; Human; Immune response; Immunization; Individual; Infection; Infective endocarditis; Knowledge; Lecithin; Life; Lipids; Lysophosphatidylcholines; Membrane; Membrane Biology; Membrane Lipids; Meningitis; Organism; Pathway interactions; Phosphatidylglycerols; Phospholipids; Phosphorylcholine; Phylogenetic Analysis; Physiological; Play; Polymers; Property; Proteome; Research; Resistance; Role; Sepsis; Serum; Signal Pathway; Signal Transduction; Streptococcus; Streptococcus mitis; Streptococcus oralis; Streptococcus pneumoniae; Stress; Structure; Surface Properties; Techniques; Time; Virulence; antimicrobial; antimicrobial peptide; base; biological adaptation to stress; cell envelope; clinically significant; combat; community acquired pneumonia; coping; cytokine; host-microbe interactions; human pathogen; inorganic phosphate; lipidome; lipidomics; lipoteichoic acid; liquid chromatography mass spectrometry; mortality; mutant; novel; novel therapeutics; opportunistic pathogen; pathogen; pathogenic bacteria; research study; response

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.

摘要 作为细胞膜的主要成分，脂类在细菌病原体的生存中扮演着多种角色。 病原体可以调整其膜脂的生化性质(如静电)以应对 随着周围环境的变化和挑战的条件。我们研究了肺炎链球菌组的血脂， 具体地说，米氏链球菌、口腔链球菌和肺炎链球菌，它们有着非常接近的系统发育 两性关系。米氏葡萄球菌和口腔沙门氏菌是引起菌血症的主要原因之一。 (血液感染)和感染性心内膜炎(心脏瓣膜感染)。肺炎链球菌是一种主要的人类 大多数儿童社区获得性肺炎和脑膜炎的病原体和 儿童死亡率是全球儿童死亡的一个主要原因。尽管这些具有临床意义 微生物及其脂类在宿主-微生物相互作用中的关键作用 群链球菌的研究还很少，对其了解也很少。用液相色谱/质谱仪 基于(LC/MS)的脂类组学，我们分析了微炎群链球菌细胞膜中的脂类，并确定了 我们提出的几种新的表面特性对于处理抗生素、抗菌剂 多肽，以及寄主内的不利条件。这个项目最重要的假设是， Mitis组链球菌显著改变其细胞膜的带电脂肪成分，影响其 与宿主的相互作用及其对抗菌素应激的反应。我们建议分析结构和 MITS群链球菌阴离子脂类(AIM 1)和两性离子脂(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)。所获得的知识将使我们更好地了解生存和 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。