# Toward targeting bacterial metabolism: Relevance, mechanism and function of DXP synthase

> **NIH NIH R56** · JOHNS HOPKINS UNIVERSITY · 2020 · $640,497

## Abstract

PROJECT SUMMARY
There is an urgent need to develop new antimicrobial strategies to combat the increasing
occurrence of drug resistance in clinical pathogens. Current antibiotics act on a limited set of
cellular processes, and the rate of new inhibitor discovery is rapidly declining. With the diminishing
arsenal of useful antibiotics, other essential cellular targets must be explored. During infection,
bacterial pathogens rapidly respond to changes in the host microenvironment by remodeling
metabolism to promote growth. These “metabolic adaptations” are crucial for pathogen survival
and pathogenicity in vivo, and are thus a promising target space for antibiotic development.
Positioned at a metabolic branch point to supply essential vitamins and isoprenoids, 1-deoxy-D-
xylulose 5-phosphate synthase (DXPS) is likely a key player in bacterial metabolic adaptation
during infection and thus a potential target. We have uncovered several unique features of DXPS
structure and mechanism that suggest it plays a potentially larger role in bacterial metabolism,
and can be selectively targeted. These insights have guided the development of tools to enable
pharmacological probing of DXPS in bacteria. In the next phase, we will: 1) investigate the effects
of targeting DXPS in the context of bacterial metabolic adaptation during infection, and validate
DXPS as a target in vivo, 2) expose new opportunities for selective inhibition by studying the
unique mechanism and conformational dynamics of DXPS, and 3) apply these insights to identify
and understand other DXPS-dependent activities. These studies could lead to discovery of other
targetable functions for antibiotic development.

## Key facts

- **NIH application ID:** 10141397
- **Project number:** 9R56AI150221-10
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Caren L. Freel Meyers
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $640,497
- **Award type:** 9
- **Project period:** 2010-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141397

## Citation

> US National Institutes of Health, RePORTER application 10141397, Toward targeting bacterial metabolism: Relevance, mechanism and function of DXP synthase (9R56AI150221-10). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10141397. Licensed CC0.

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