# Biosynthesis and regulation of a unipolar polysaccharide in Agrobacterium

> **NIH NIH R01** · TRUSTEES OF INDIANA UNIVERSITY · 2020 · $342,450

## Abstract

PROJECT SUMMARY
 The establishment of productive, stable surface interactions is an important process for bacteria, that
can lead to formation of the adherent communities known as biofilms. These assemblages are challenges in
agricultural, industrial and medical settings, and are intrinsically tolerant to many antimicrobial therapies. For a
number of bacteria in the large and diverse Alphaproteobacteria (APB) group, attachment to surfaces and to
other cells requires production of a structure comprised of polysaccharide localized to a single cellular pole. In
the model pathogen Agrobacterium tumefaciens this structure is called the unipolar polysaccharide (UPP).
Polar adhesins similar to the UPP are widespread among the APB, including other pathogens and symbionts,
and the A. tumefaciens UPP is therefore a representative model for these diverse bacteria. Among these, the
stalked bacterium Caulobacter crescentus produces a similar structure called the holdfast at the stalk tip, and
although it has been well studied, remains poorly understood and is less broadly representative than the UPP.
These polar polysaccharides can drive stable surface attachment and host interactions. In A. tumefaciens the
UPP is comprised of at least two distinct polysaccharide species, and the genes required for synthesis suggest
that there may be overlapping biosynthesis pathways. We aim to determine how A. tumefaciens coordinates
and regulates production of these polysaccharides during surface colonization, including dynamic localization
of the biosynthetic complexes. Production of the A. tumefaciens UPP is strictly regulated by contact with the
surface, and cells rarely if ever produce the UPP when free-swimming. The proposed studies will dramatically
improve our current understanding of UPP properties and biosynthesis, and will elucidate its regulation via a
network of intracellular signal cascades, its surface-dependent polar localization, and other environmental
signals that affect its production, and thereby attachment. At the core of this control network is the ubiquitous
bacterial second messenger cyclic diguanylate monophosphate, which regulates UPP production. Among the
primary UPP regulatory mechanisms are a novel signaling pathway involving small metabolites called pterins,
and the response to low pH. The project utilizes an extensive collection of genetic mutants and variants,
quantitative microscopic imaging approaches, genomic technology, and sophisticated biochemical approaches
to illuminate the cellular processes that promote attachment via the UPP. The findings generated will contribute
to the understanding of the motile to sessile transition and initiation of biofilm formation. We will characterize
the biosynthesis of a novel biological adhesive(s) and a potential antimicrobial target, and will reveal how
bacterial cells control production of these important products to promote surface interactions that lead to biofilm
formation. Our findings will provi...

## Key facts

- **NIH application ID:** 9994938
- **Project number:** 5R01GM120337-04
- **Recipient organization:** TRUSTEES OF INDIANA UNIVERSITY
- **Principal Investigator:** WILLIAM C FUQUA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $342,450
- **Award type:** 5
- **Project period:** 2017-09-08 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994938

## Citation

> US National Institutes of Health, RePORTER application 9994938, Biosynthesis and regulation of a unipolar polysaccharide in Agrobacterium (5R01GM120337-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9994938. Licensed CC0.

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