# Bacterial cell wall synthesis, shape and septation

> **NIH NIH R01** · UNIV OF ARKANSAS FOR MED SCIS · 2021 · $503,736

## Abstract

PROJECT SUMMARY
Bacterial cell shape is of fundamental and medical importance, contributing to survival and virulence by
influencing nutrient uptake, cell-to-surface attachment, motility, differentiation, and resistance to predation or
host immunity. Furthermore, morphological studies are illuminating previously unrecognized interactions
among diverse biochemical events that drive bacterial growth. In short, morphology plays crucial roles in
bacterial physiology, ecology and pathogenesis, and serves as a window into cell biology. Most bacteria
determine their shapes by making a peptidoglycan cell wall, and interfering with this structure is one of the
most important targets for anti-bacterial therapy. Despite decades of work, there remain large gaps in
understanding how peptidoglycan synthesis is integrated with related metabolic pathways. One integration
point is the carrier molecule undecaprenyl-phosphate (Und-P), which helps synthesize peptidoglycan and other
oligosaccharides. It has become clear that Und-P and its derivatives form a vital nexus that must be
characterized in detail to help combat increasing antibiotic resistance. To this end we propose the following
Aims. Aim 1] Determine how Und-P management alters bacterial physiology and biochemistry. Und-P and
its homologues transport numerous compounds and polymers across the cytoplasmic membranes of cells in all
biological kingdoms, including archaea and eukaryotes. Because the end-products are synthesized by diverse
routes, the carrier must be shared among several biochemical pathways, but how this is accomplished is
unknown. It is, however, vital – if Und-P is sequestered in one pathway, less is available for peptidoglycan
synthesis and cells grow poorly or die. We will develop tools to monitor the amounts of Und-P in living cells
and will determine how competition for Und-P affects bacterial growth and the operation of each pathway.
Aim 2] Identify and characterize new and little-known Und-P-utilizing pathways. Although several Und-P-
dependent pathways are known, there are many for which little information is available and, undoubtedly,
others we know nothing about at all. We will characterize those pathways projected to exist in Escherichia coli
and will initiate genetic screens to look for others. Aim 3] Identify and characterize cell shape mutants.
Historically, most morphological mutants were discovered while studying something else. Here, we will
continue to use flow cytometry to isolate such mutants, to identify new mechanisms that affect bacterial shape.
We will also characterize more fully the mutants we already have in hand. In summary, these tools and
approaches will enable us to investigate, faster and in greater depth, the mysteries surrounding Und-P
utilization and its interactions with basic metabolic pathways. In addition, the work will create a well-
developed bacterial model that will inform and enhance similar investigations in many other organisms.

## Key facts

- **NIH application ID:** 10062979
- **Project number:** 5R01GM061019-21
- **Recipient organization:** UNIV OF ARKANSAS FOR MED SCIS
- **Principal Investigator:** Daniel E Voth
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $503,736
- **Award type:** 5
- **Project period:** 2000-03-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10062979

## Citation

> US National Institutes of Health, RePORTER application 10062979, Bacterial cell wall synthesis, shape and septation (5R01GM061019-21). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10062979. Licensed CC0.

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