# Peptidoglycan remodeling during zinc starvation in Acinetobacter baumannii

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2020 · $5,841

## Abstract

PROJECT SUMMARY
Acinetobacter baumannii is a Gram-negative opportunistic pathogen that causes a range of diseases and is one
of the major infectious agents responsible for ventilator-associated pneumonia. In order for A. baumannii to
cause disease, it must acquire nutrient zinc from its environment and compete with the host for this essential
metal. Keeping with this, A. baumannii upregulates a variety of zinc acquisition genes in response to nutrient
limitation. A highly induced gene during zinc limitation encodes a putative D-alanine-D-alanine carboxypeptidase
which we have named zrlA, which is an enzyme class involved in peptidoglycan remodeling. While these
carboxypeptidases are broadly classified as being involved in cell wall maintenance, their importance in bacterial
pathogenesis and their contribution to nutrient acquisition is not well-defined. Genetic inactivation of zrlA results
in a significant growth defect during zinc limitation and reduces fitness in a murine model of pneumonia.
Furthermore, this strain is extremely sensitive to antibiotic exposure, suggesting that ZrlA contributes to both
nutrient zinc homeostasis and maintaining the barrier function of the cellular envelope. Therefore, we predict that
ZrlA is specifically induced during zinc starvation to modify peptidoglycan in an effort to promote zinc acquisition
and provide resistance to extracellular stress. This prediction will be tested through two specific aims. In Specific
Aim 1, the contribution of ZrlA to overcoming zinc starvation will be determined by assessing alterations in zinc
acquisition systems and uptake. Experiments proposed in Specific Aim 2 will more specifically dissect the
impact of ZrlA on peptidoglycan architecture and cellular integrity. This aim will combine biochemical techniques
with advanced microscopy to determine structural components of the bacterial cell envelope and the niche in
which ZrlA contributes to this shape. Taken together, these findings will have broad implications for
understanding the mechanism bacterial pathogens employ to acquire zinc despite nutrient limitation within the
vertebrate host, and provide exciting targets for antimicrobial therapy development involving bacterial metal
acquisition.

## Key facts

- **NIH application ID:** 9859308
- **Project number:** 5F31AI136255-03
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Zachery Lonergan
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $5,841
- **Award type:** 5
- **Project period:** 2018-02-14 → 2020-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9859308

## Citation

> US National Institutes of Health, RePORTER application 9859308, Peptidoglycan remodeling during zinc starvation in Acinetobacter baumannii (5F31AI136255-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9859308. Licensed CC0.

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