# Permeability Barriers of Gram-negative Pathogens and Approaches to Bypass Them

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA · 2020 · $498,640

## Abstract

Permeability barriers of Gram-negative pathogens and approaches to bypass
them
A major source of resistance in Gram-negative species is the permeability barrier created by a
synergistic action of slow uptake and active efflux of antibiotics across the outer membrane. The
proposed research will address a critical need to understand penetration across the cell
envelope of Gram-negative species and to develop antibiotics affective against these
pathogens. In preliminary studies, we established novel mathematical and empirical approaches
to analyze drug uptake across a two-membrane barrier with active efflux. Based on these
results, we formulated a hypothesis that permeation and hence activities of antibiotics are
affected by bacterial barriers and active efflux differently and that these differences are defined
by physicochemical properties of antibiotics. To critically test this hypothesis, we will apply the
new formalism and methods to analyze permeability barriers of Pseudomonas aeruginosa,
Acinetobacter baumannii and Burkholderia spp. that differ significantly in the composition of
their outer membranes and efflux pumps. These pathogens are notorious for their virtually
unbreachable permeability barriers. Our goal is to establish structure-activity relationships
between drug uptake, efflux and inhibitory activities for a select library of compounds in the
context of barriers with different permeability properties. The proposed studies will define the
limits of barriers and compounds and will create a framework for optimization of antibiotics
targeting the “impermeable” pathogens.

## Key facts

- **NIH application ID:** 9914090
- **Project number:** 5R01AI132836-04
- **Recipient organization:** UNIVERSITY OF OKLAHOMA
- **Principal Investigator:** HELEN I ZGURSKAYA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $498,640
- **Award type:** 5
- **Project period:** 2017-05-08 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9914090

## Citation

> US National Institutes of Health, RePORTER application 9914090, Permeability Barriers of Gram-negative Pathogens and Approaches to Bypass Them (5R01AI132836-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9914090. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*