# Solving a Multidrug Resistance Puzzle: Complete Loss of Lipooligosaccharide

> **NIH NIH R21** · UNIVERSITY OF TEXAS ARLINGTON · 2020 · $186,917

## Abstract

Project Summary/Abstract
Bacterial pathogens exploit various molecular mechanisms to survive adverse environmental conditions.
Gram-negative bacteria modify their outer membrane, which is an asymmetric bilayer consisting of inner leaflet
glycerophospholipids and essential outer leaflet lipooligosaccharide or lipopolysaccharide. Acinetobacter
baumannii is a Gram-negative nosocomial pathogen that thrives in healthcare settings because of its ability to
develop resistance to antibiotics. Multidrug resistant A. baumannii have become widespread over the past
decade and last-line antibiotics such as colistin, which targets the lipid A domain of lipooligosaccharide in the
outer membrane, has been increasingly prescribed to treat infections. While colistin resistance was once rare,
A. baumannii has developed a unique resistance mechanism. A. baumannii can completely shut down lipid A
biosynthesis to develop multidrug resistance to many prescribed antibiotics, including colistin. This finding is
surprising because lipopolysaccharide was thought to be required for Gram-negative viability, but this
mechanism proves otherwise. Molecular factors that contribute to this multidrug resistance phenotype are not
understood and treatment options have not been explored.
The overall objective of this proposal is to characterize and understand a novel multidrug resistance
mechanism. The Specific Aims of this proposal are to (i) Characterize the outer membrane proteins that
support LOS- A. baumannii survival and (ii) characterization of the BaeSR two-component system and its
regulatory products. Completion of these AIMS will advance our body of knowledge to understand the
essentiality of lipid A in Gram-negative bacteria and provide understanding of a molecular mechanism required
for a novel multidrug resistance mechanism. Furthermore, the findings from this proposal could also potentially
lead to development of novel therapeutics and improved vaccines.

## Key facts

- **NIH application ID:** 9939446
- **Project number:** 5R21AI146829-02
- **Recipient organization:** UNIVERSITY OF TEXAS ARLINGTON
- **Principal Investigator:** Joseph Michael Boll
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $186,917
- **Award type:** 5
- **Project period:** 2019-06-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939446

## Citation

> US National Institutes of Health, RePORTER application 9939446, Solving a Multidrug Resistance Puzzle: Complete Loss of Lipooligosaccharide (5R21AI146829-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9939446. Licensed CC0.

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