# Permeability barriers of Gram-negative pathogens and approaches to bypass them

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA · 2024 · $463,073

## Abstract

Project Description
Antibiotics effective against Gram-negative pathogens are a critical area of unmet need. Infections caused by
these pathogens are not only difficult to treat but finding new therapies to overcome Gram-negative resistance
is also a challenge. The major obstacle in antibiotic discovery pipeline is the lack of understanding how to breach
antibiotic permeability barriers of these pathogens. Furthermore, these permeability barriers are one of the major
resistance mechanisms to antibiotics in clinical settings. The long-term goal of this project is to establish
structure-activity relationships between drug uptake, efflux and inhibitory activities of antibiotics in the context of
permeation barriers with different properties. During the previous funding period, we made significant progress
in understanding the functional and regulatory interactions between efflux pumps and cellular membranes in
Pseudomonas aeruginosa, Acinetobacter baumannii and Burkholderia thailandensis. These pathogens are
notorious for their virtually unbreachable permeability barriers and understanding how these barriers can be
penetrated is critical for successful development of new therapeutics and for effective management of emerging
antibiotic resistance. The major objective of this application is to characterize how changes in the expression
and functions of efflux pumps are integrated into bacterial physiology and how drug permeability barriers are
modified during bacterial infections. To achieve this objective, we will analyze relationships between efflux pumps
and permeability barriers in P. aeruginosa, A. baumannii and B. thailandensis pathogens that differ significantly
in the composition of their outer membranes and efflux pumps. We will next extend these relationships into the
bacteria-host cell interface and will determine how bacterial infections affects drug fluxes across both bacterial
and host cell membranes.

## Key facts

- **NIH application ID:** 10830353
- **Project number:** 5R01AI132836-07
- **Recipient organization:** UNIVERSITY OF OKLAHOMA
- **Principal Investigator:** HELEN I ZGURSKAYA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $463,073
- **Award type:** 5
- **Project period:** 2017-05-08 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10830353

## Citation

> US National Institutes of Health, RePORTER application 10830353, Permeability barriers of Gram-negative pathogens and approaches to bypass them (5R01AI132836-07). Retrieved via AI Analytics 2026-05-31 from https://api.ai-analytics.org/grant/nih/10830353. Licensed CC0.

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