Function of the Klebsiella pneumoniae RND efflux systems

肺炎克雷伯菌 RND 外排系统的功能

基本信息

项目摘要

PROJECT SUMMARY/ABSTRACT The widespread use of antibiotics has driven the evolution and global dissemination of resistance genes among pathogenic bacteria including Klebsiella pneumoniae which has evolved resistance to all clinically relevant antibiotics. K. pneumoniae is leading cause of nosocomial infections and has a high mortality rate and multiple drug resistance has made K. pneumoniae infections difficult to treat. In addition to drug resistance, hypervirulent strains of K. pneumoniae that cause community acquired invasive infections in healthy individuals have emerged globally. The devastating consequences of K. pneumoniae infection, combined with the global dissemination of resistance and virulence traits among K. pneumoniae, have led to K. pneumoniae being recognized as an urgent health threat by the World Health Organization and the Centers for Disease Control. This has highlighted the critical need for the development of new therapeutic approaches to treat antimicrobial resistant infections. In this application we present preliminary data showing that multiple drug efflux systems belonging to the Resistance-Nodulation-Sensing (RND) superfamily contribute to the evolution of multiple antibiotic resistance in K. pneumoniae. In addition to their role in antimicrobial resistance, RND efflux systems have also been shown to be required for multiple other phenotypes including phenotypes required for virulence, but the mechanisms involved in this process are largely unknown. In this proposal we will test the hypothesis that the K. pneumoniae RND efflux systems are essential for multiple antibiotic resistance and pathogenesis. We propose two aims to test our hypothesis. In aim 1 we will define the function of the individual K. pneumoniae RND efflux systems in antimicrobial resistance and determine their effect on homeostasis. In aim 2 we will investigate the contribution of the K. pneumoniae RND transporters to virulence-associated phenotypes in vitro and in vivo pathogenic potential in the Galleria mellonella larvae infection model. Completion of this work will define the function of the K. pneumoniae RND efflux systems in antimicrobial resistance, biology and pathogenesis and illuminate novel aspects of K. pneumoniae biology that may lead to the development of novel therapeutic approaches to treat antibiotic resistant K. pneumoniae infections.
项目总结/文摘

项目成果

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JAMES Edward BINA其他文献

JAMES Edward BINA的其他文献

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{{ truncateString('JAMES Edward BINA', 18)}}的其他基金

Function of the Klebsiella pneumoniae RND efflux systems
肺炎克雷伯菌 RND 外排系统的功能
  • 批准号:
    10525108
  • 财政年份:
    2022
  • 资助金额:
    $ 23.85万
  • 项目类别:
Environmental adaptation by Vibrio cholerae
霍乱弧菌的环境适应
  • 批准号:
    10633541
  • 财政年份:
    2018
  • 资助金额:
    $ 23.85万
  • 项目类别:
Environmental adaptation by Vibrio cholerae
霍乱弧菌的环境适应
  • 批准号:
    10656646
  • 财政年份:
    2018
  • 资助金额:
    $ 23.85万
  • 项目类别:
Environmental adaptation by Vibrio cholerae
霍乱弧菌的环境适应
  • 批准号:
    9975688
  • 财政年份:
    2018
  • 资助金额:
    $ 23.85万
  • 项目类别:
Environmental adaptation by Vibrio cholerae
霍乱弧菌的环境适应
  • 批准号:
    10228740
  • 财政年份:
    2018
  • 资助金额:
    $ 23.85万
  • 项目类别:
Environmental adaptation by Vibrio cholerae
霍乱弧菌的环境适应
  • 批准号:
    9755358
  • 财政年份:
    2018
  • 资助金额:
    $ 23.85万
  • 项目类别:
Role of cyclo(Phe-Pro) in Vibrio cholerae virulence factor production
环(Phe-Pro)在霍乱弧菌毒力因子产生中的作用
  • 批准号:
    8186812
  • 财政年份:
    2011
  • 资助金额:
    $ 23.85万
  • 项目类别:
Role of cyclo(Phe-Pro) in Vibrio cholerae virulence factor production
环(Phe-Pro)在霍乱弧菌毒力因子产生中的作用
  • 批准号:
    8423427
  • 财政年份:
    2011
  • 资助金额:
    $ 23.85万
  • 项目类别:
Role of cyclo(Phe-Pro) in Vibrio cholerae virulence factor production
环(Phe-Pro)在霍乱弧菌毒力因子产生中的作用
  • 批准号:
    8258229
  • 财政年份:
    2011
  • 资助金额:
    $ 23.85万
  • 项目类别:
Role of cyclo(Phe-Pro) in Vibrio cholerae virulence factor production
环(Phe-Pro)在霍乱弧菌毒力因子产生中的作用
  • 批准号:
    8449172
  • 财政年份:
    2011
  • 资助金额:
    $ 23.85万
  • 项目类别:

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