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）：鼻咽的定植是病原体肺炎链球菌的疾病的先决条件。具有> 90种不同的囊型血清型，7价偶联物肺炎球菌疫苗（PCV7）的最初成功已被血清型替代的报道所掩盖，导致血清型替代的报道导致定殖和疾病和先前罕见的菌株。这表明肺炎球菌之间的种内竞争发生在鼻咽内，并且通过PCV7诱导的牛群免疫失去了竞争性菌株的丧失导致先前竞争的菌株的出现。该项目使用两个目的来解决肺炎链球菌制造的抗菌肽的贡献，称为肺炎葡萄球菌对种内竞争的贡献。第一个目的是针对肺炎表达调节的机理，肺炎素表达涉及转录和转录后水平的修饰。将研究调节回路，并特别强调定殖期间的表达状态。第二个目的将集中于影响各种肺炎MN同种型活性谱的因素，并描述了这些肽通过肉体菌株同时定殖的小鼠模型中可恶的菌株清除定殖的能力。该应用程序描述了一项为期4年的计划，旨在为Suzanne Dawid博士提供成为微生物发病机理领域的独立科学家所需的技能。 Dawid博士已经完成了小儿感染疾病的研究金，将由细菌发病机理领域的领导者Jeffrey Weiser博士进行指导，特别关注肺炎链球菌定殖。该项目涉及在遗传学和微生物发病机理以及分子生物学，生物化学和体内建模领域的深入实验室经验中的教学研究。相关性：由肺炎链球菌的产生介导的肺炎链球菌分离株之间存在的种内竞争，称为肺炎蛋白的抗菌肽可能解释了种群广泛疫苗接种后先前罕见菌株的出现。这项对推动这一竞争力量的力量的详细研究将有助于我们理解成功定植的微生物生态学和复杂相互作用，这是该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