# Unraveling Bacterial Cell Wall Biosynthesis and Sensing via Synthetic Analogs

> **NIH NIH R35** · UNIVERSITY OF VIRGINIA · 2020 · $382,082

## Abstract

Project Summary
 Every year in the United States, over two million people are afflicted with bacterial infections
resistant to FDA-approved antibiotics. More than 23,000 of these patients die as a result of such
infections. The rapid surge in drug-resistant bacteria has now become one of the primary public
health crises of the 21st century. The large majority of antibiotics in use today were discovered
many decades ago. In order to counter the rapid rise in drug-resistance in bacteria, new drug
targets and diagnostic tests are urgently needed. The bacterial cell wall has proven to be a rich
source of antibiotic drug discovery. However, there are fundamental aspects of bacterial cell
wall assembly and its interaction with the host organism that are yet to be fully elucidated. Our
proposed strategies will use synthetic chemistry as a platform to construct cell wall analogs that
metabolically label live bacteria and mimic key aspects of cell wall architecture. We anticipate
that interrogation of cell wall remodeling and processing in pathogenic bacteria will guide the
design of next-generation antibiotics that circumvent resistance mechanisms. Furthermore, the
development of probes to systematically characterize cell wall sensing and host distribution will
add fundamental knowledge to bacterial pathogenesis and human microbiome maintenance.
We will focus on: (1) the contribution of individual enzymes to the overall drug resistant
phenotype in response to antibiotics in live bacterial cells, (2) key interactions by bacterial
membrane-anchored proteins to Lipid II (the bottle-neck point of cell wall biosynthesis), (3) the
molecular recognition of cell wall by cell wall receptors on human immune cells, and (4) the
processing of disseminated bacterial-derived membrane vesicles, which contain cell wall
fragments, by human immune cells.

## Key facts

- **NIH application ID:** 9989131
- **Project number:** 5R35GM124893-05
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Marcos M. Pires
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $382,082
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989131

## Citation

> US National Institutes of Health, RePORTER application 9989131, Unraveling Bacterial Cell Wall Biosynthesis and Sensing via Synthetic Analogs (5R35GM124893-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9989131. Licensed CC0.

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