Mechanisms of intraspecies Competition in Streptococcus pneumoniae.

肺炎链球菌种内竞争机制。

• 批准号: 7739499
• 负责人: Suzanne Rachel Dawid
• 金额: $ 13.39万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-15 至 2011-05-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7739499
• 关键词: Address; Alleles; Biochemistry; Childhood; Communicable Diseases; Complex; Disease; Ecology; Fellowship; Genes; Herd Immunity; Immunity; In Vitro; Laboratories; Mediating; Mentors; Microbial Genetics; Modification; Molecular Biology; Nasopharynx; Pathogenesis; Peptides; Pneumococcal 7-Valent Conjugate Vaccine; Population; Production; Regulation; Reporting; Scientist; Serotyping; Streptococcus pneumoniae; Vaccination; Variant; antimicrobial; antimicrobial peptide; design; driving force; experience; in vivo; in vivo Model; microbial; mouse model; pathogen; programs; skills; success

DESCRIPTION (provided by applicant): Colonization of the nasopharynx is a prerequisite to disease with the pathogen Streptococcus pneumoniae. With >90 different capsular serotypes, the initial success of the 7-valent conjugate pneumococcal vaccine (PCV7) has been overshadowed by reports of serotype replacement resulting in colonization and disease with previously rare strains. This suggests that intraspecies competition among pneumococci occurs in the nasopharynx, and the loss of competitive strains through PCV7 induced herd immunity has resulted in the emergence of previously out competed strains. This project uses two aims to address the contribution of antimicrobial peptides made by S. pneumoniae called pneumocins to intraspecies competition. The first aim addresses the mechanism of regulation of pneumocin expression which involves modifications at the transcriptional and post transcriptional level. The regulatory circuit will be studied with a particular emphasis on the state of expression during colonization. The second aim will focus on factors influencing the spectrum of activity of the various pneumocin MN isotypes as well as describing the ability of these peptides to clear colonization by suseptible strains in a mouse model of simultaneous colonization by mutliple strains. This application describes a 4-year program designed to provide Dr. Suzanne Dawid with the skills required to become an independent scientist in the field of microbial pathogenesis. Dr. Dawid has completed a fellowship in pediatric infectious diseases and will be mentored by Dr. Jeffrey Weiser, a leader in the field of bacterial pathogenesis with a particular focus on S. pneumoniae colonization. The project involves didactic study in the fields of genetics and microbial pathogenesis as well as in-depth laboratory experience in molecular biology, biochemistry and in vivo modeling. Relevance: Preexisting intraspecies competition between isolates of S. pneumoniae mediated by the production of antimicrobial peptides called pneumocins may explain the emergence of previously rare strains following widespread vaccination of the population. This detailed study of the forces driving this competition will aid in our understanding of microbial ecology and complex interactions involved in successful colonization, the initial step in all disease by this major pathogen.

描述(由申请人提供)：鼻咽的定植是肺炎链球菌疾病的先决条件。由于有90种不同的衣壳血清型，七价结合肺炎球菌疫苗(PCV7)的初步成功被有关血清型替换导致定居和以前罕见菌株的疾病的报道所笼罩。这表明肺炎球菌之间的种内竞争发生在鼻咽，而PCV7诱导的群体免疫导致竞争菌株的丧失，导致了以前竞争菌株的出现。这个项目使用两个目标来解决肺炎链球菌产生的抗菌肽对种内竞争的贡献。第一个目的是研究调节肺炎蛋白表达的机制，它涉及转录和转录后水平的修饰。对调节回路的研究将特别强调在殖民期间的表达状态。第二个目标将集中于影响不同肺炎蛋白MN亚型活性谱的因素，以及描述这些多肽在多个菌株同时定植的小鼠模型中清除易感菌株定植的能力。本申请描述了一个为期4年的项目，旨在为Suzanne Dawid博士提供成为微生物发病机制领域的独立科学家所需的技能。Dawid博士已经完成了儿科传染病的研究，并将接受Jeffrey Weiser博士的指导，Jeffrey Weiser博士是细菌发病机制领域的领先者，特别关注肺炎链球菌的定植。该项目涉及遗传学和微生物发病机制领域的教学研究，以及在分子生物学、生物化学和活体建模方面的深入实验室经验。相关性：肺炎链球菌分离株之间先前存在的种内竞争通过产生称为肺炎菌素的抗菌肽来调节，这可能解释了在人群广泛接种疫苗后出现以前罕见的菌株的原因。对推动这场竞争的力量的详细研究将有助于我们了解成功定植所涉及的微生物生态学和复杂的相互作用，这是这种主要病原体在所有疾病中的第一步。

项目成果

Conserved mutations in the pneumococcal bacteriocin transporter gene, blpA, result in a complex population consisting of producers and cheaters.

肺炎球菌细菌素转运蛋白基因 blpA 的保守突变导致了一个由生产者和作弊者组成的复杂群体。

• DOI: 10.1128/mbio.00179-11
• 发表时间: 2011
• 期刊: mBio
• 影响因子: 6.4
• 作者: Son,MatthewR;Shchepetov,Mikhail;Adrian,PeterV;Madhi,ShabirA;deGouveia,Linda;vonGottberg,Anne;Klugman,KeithP;Weiser,JeffreyN;Dawid,Suzanne
• 通讯作者: Dawid,Suzanne