# Function of the Klebsiella pneumoniae RND efflux systems

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $198,490

## Abstract

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.

## Key facts

- **NIH application ID:** 10525108
- **Project number:** 1R21AI166889-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** JAMES Edward BINA
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $198,490
- **Award type:** 1
- **Project period:** 2022-06-17 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10525108

## Citation

> US National Institutes of Health, RePORTER application 10525108, Function of the Klebsiella pneumoniae RND efflux systems (1R21AI166889-01A1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10525108. Licensed CC0.

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