DISSEMINATION OF MACROLIDE RESISTANCE ELEMENTS IN STREPTOCOCCUS PNEUMONIAE

肺炎链球菌中大环内酯类耐药元件的传播

基本信息

  • 批准号:
    10027021
  • 负责人:
  • 金额:
    $ 15.74万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-03-06 至 2021-02-28
  • 项目状态:
    已结题

项目摘要

Abstract Streptococcus pneumoniae (Spn) colonizes the epithelial surface of the human nasopharynx in early childhood and remains a significant cause of respiratory illness. Globally, Spn causes 15 million cases of pneumococcal disease (PD) each year leading to approximately ∼0.5 million deaths in children. Treatment of PD has been hindered by emergence of antimicrobial resistance, including the resistance to macrolides. Most pneumococcal macrolide resistance is conferred by Erm(B), the RNA methylase, and/or efflux/ribosomal protection mediated by Mef(E)/Mel on the macrolide efflux genetic assembly (Mega) element. The Mega element, related to Tn916 conjugative transposons but does not encode putative recombinases, has integrated into at least four loci in the pneumococcal chromosome, Mega classes I–IV. Molecular epidemiological studies demonstrated a higher prevalence of isolates containing the class II Mega, which is not caused by clonal expansion. Moreover, a wide array of complex Tn916 related mobile genetic elements, termed integrative and conjugative elements (ICEs), has emerged that also facilitate dissemination of macrolide resistance (both ermB and Mega) and additional antibiotic resistance markers. While acquisition of Mega and ICE-encoded resistance presumably occurs during colonization of the human nasopharynx, the efficiency and the specific mechanisms by which Mega elements and ICEs spread among pneumococci in the nasopharynx is not well understood. Our novel discovery of pneumococcal unidirectional transformation in the human nasopharyngeal biofilms has provided new insights on gene transfer in S. pneumoniae. In this proposal, using an established model of human nasopharyngeal consortial biofilms and the newly characterized uni-directional gene transfer phenomenon, we will determine the mechanisms and frequencies of macrolide resistance dissemination mediated by the Mega elements and ICEs. In Aim 1 we will evaluate whether genomic recombination hot spots or strain background, influence the recombination frequency (rF) and account for different prevalence among Mega classes. Donor strains engineered with each of the four Mega classes and defined pneumococcal clinical isolates containing the Mega classes will be conducted to assess the contribution of genomic loci and strain backgrounds, respectively. Both the rF and the specific recombination sites will be defined in recombinants. In aim 2 we will investigate whether conjugation or recombination via transformation, drives the mobilization of ICE- encoded macrolide resistant determinants. The molecular mechanism of ICE-dissemination among pneumococci will be further investigated using mutants with inactivated transposon-encoded mobilization proteins and proteins mediating competence. Identifying the horizontal dissemination mechanisms and frequencies of the two-major macrolide resistance genetic determinants will be valuable for new interventions aimed at decreasing the burden of antibiotic resistance dissemination in S. pneumoniae.
摘要

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

DAVID S STEPHENS其他文献

DAVID S STEPHENS的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('DAVID S STEPHENS', 18)}}的其他基金

DISSEMINATION OF MACROLIDE RESISTANCE ELEMENTS IN STREPTOCOCCUS PNEUMONIAE
肺炎链球菌中大环内酯类耐药元件的传播
  • 批准号:
    9888324
  • 财政年份:
    2019
  • 资助金额:
    $ 15.74万
  • 项目类别:
CTSA INFRASTRUCTURE FOR AIDS RESEARCH
CTSA 艾滋病研究基础设施
  • 批准号:
    8366095
  • 财政年份:
    2011
  • 资助金额:
    $ 15.74万
  • 项目类别:
CTSA INFRASTRUCTURE FOR AIDS RESEARCH
CTSA 艾滋病研究基础设施
  • 批准号:
    8366091
  • 财政年份:
    2011
  • 资助金额:
    $ 15.74万
  • 项目类别:
CTSA INFRASTRUCTURE FOR CLINICAL TRIALS
CTSA 临床试验基础设施
  • 批准号:
    8366093
  • 财政年份:
    2011
  • 资助金额:
    $ 15.74万
  • 项目类别:
ATLANTA CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE
亚特兰大临床与转化科学研究所
  • 批准号:
    8366094
  • 财政年份:
    2011
  • 资助金额:
    $ 15.74万
  • 项目类别:
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCH
CTSA 儿科研究基础设施
  • 批准号:
    8366092
  • 财政年份:
    2011
  • 资助金额:
    $ 15.74万
  • 项目类别:
CTSA INFRASTRUCTURE FOR AIDS RESEARCH
CTSA 艾滋病研究基础设施
  • 批准号:
    8173821
  • 财政年份:
    2010
  • 资助金额:
    $ 15.74万
  • 项目类别:
CTSA INFRASTRUCTURE FOR CLINICAL TRIALS
CTSA 临床试验基础设施
  • 批准号:
    8173819
  • 财政年份:
    2010
  • 资助金额:
    $ 15.74万
  • 项目类别:
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCH
CTSA 儿科研究基础设施
  • 批准号:
    8173818
  • 财政年份:
    2010
  • 资助金额:
    $ 15.74万
  • 项目类别:
CTSA INFRASTRUCTURE FOR AIDS RESEARCH
CTSA 艾滋病研究基础设施
  • 批准号:
    8173817
  • 财政年份:
    2010
  • 资助金额:
    $ 15.74万
  • 项目类别:

相似海外基金

Macrolide resistance transfer in Streptococcus pyogenes
化脓性链球菌中的大环内酯类耐药性转移
  • 批准号:
    10474268
  • 财政年份:
    2021
  • 资助金额:
    $ 15.74万
  • 项目类别:
DISSEMINATION OF MACROLIDE RESISTANCE ELEMENTS IN STREPTOCOCCUS PNEUMONIAE
肺炎链球菌中大环内酯类耐药元件的传播
  • 批准号:
    9888324
  • 财政年份:
    2019
  • 资助金额:
    $ 15.74万
  • 项目类别:
Elucidation of a novel mechanism of macrolide resistance in Mycobacterium abscessus
阐明脓肿分枝杆菌大环内酯类耐药的新机制
  • 批准号:
    9804856
  • 财政年份:
    2019
  • 资助金额:
    $ 15.74万
  • 项目类别:
Elucidation of macrolide resistance mechanism and virulence of Streptococcus pyogenes focused on phage DNA
以噬菌体 DNA 阐明化脓性链球菌的大环内酯类耐药机制和毒力
  • 批准号:
    16K08782
  • 财政年份:
    2016
  • 资助金额:
    $ 15.74万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Mechanism of Macrolide Resistance Through 2'-Macrolide Phosphotransferase Type I and II
通过 2-大环内酯磷酸转移酶 I 型和 II 型产生大环内酯耐药机制
  • 批准号:
    482906-2015
  • 财政年份:
    2015
  • 资助金额:
    $ 15.74万
  • 项目类别:
    University Undergraduate Student Research Awards
Mechanism of Macrolide Resistance Through 2'-Macrolide Phosphotransferase Type 1 and 2
通过 2-大环内酯磷酸转移酶 1 型和 2 型产生大环内酯耐药性的机制
  • 批准号:
    331573
  • 财政年份:
    2014
  • 资助金额:
    $ 15.74万
  • 项目类别:
    Studentship Programs
Functional Consequence of Macrolide Resistance Mutations in T. pallidum
梅毒螺旋体大环内酯类抗性突变的功能后果
  • 批准号:
    8225241
  • 财政年份:
    2011
  • 资助金额:
    $ 15.74万
  • 项目类别:
Functional Consequence of Macrolide Resistance Mutations in T. pallidum
梅毒螺旋体大环内酯类抗性突变的功能后果
  • 批准号:
    8094182
  • 财政年份:
    2011
  • 资助金额:
    $ 15.74万
  • 项目类别:
Molecular basis of macrolide resistance among Pasteurella multocida and Mannheimia haemolytica isolates
多杀性巴氏杆菌和溶血性曼海姆氏菌对大环内酯类药物耐药的分子基础
  • 批准号:
    144713519
  • 财政年份:
    2009
  • 资助金额:
    $ 15.74万
  • 项目类别:
    Research Grants
Emerging Macrolide Resistance in Mycoplasma Pneumoniae
肺炎支原体中新出现的大环内酯类耐药性
  • 批准号:
    7712312
  • 财政年份:
    2009
  • 资助金额:
    $ 15.74万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了