# Mechanisms and consequence of helical shape generation in Helicobacter pylori

> **NIH NIH R01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $475,685

## Abstract

Bacteria come in many shapes, which may enhance motility, biofilm formation, nutrient uptake, and
pathogenesis. However, these functional consequences of shape have not been well studied, owing in part to a
paucity of tools to manipulate bacterial cell shape. To probe how form (cell shape) drives function (radiation to
diverse niches), we must first understand how shape is generated. Bacterial shapes varying from spheres to
rods to helices all arise from the same cell wall polymer: peptidoglycan (PG). The PG wall surrounds the cell to
contain turgor pressure. The major hypothesis in the field holds that diverse shapes arise from different patterns
of PG synthesis. Indeed Escherichia coli, a straight rod, and Caulobacter crescentus and Vibrio cholerae, curved
rods, require cytoskeletal proteins to modulate their PG synthesis patterns. Mechanisms that create helical cells,
seen in multiple lineages of bacteria, have not been elucidated.
Helicobacter pylori has emerged as the leading model for the study of helical shape. This bacterium persistently
colonizes the human stomach causing chronic inflammation and clinical pathologies ranging from peptic ulcers
to gastric cancer, the world’s third leading cause of cancer mortality in 2012 [2]. We isolated mutants with stable
non-helical shapes, and our work demonstrating their defects in stomach colonization presented the first
experimental evidence for a link between cell shape and bacterial infectivity that has now been extended to other
bacteria (Vibrio, Campylobacter) [3-5]. However, we only have a cursory understanding of the importance of
shape in initial infection and do not understand how altered shape impacts long-term colonization, niche
acquisition, or host immune responses.
Furthermore, H. pylori’s strategy for maintaining helical shape differs significantly from bacteria studied thus far.
Five of our shape mutants map to confirmed PG hydrolases suggesting a model whereby helical shape arises
from structural modification of PG rather than modulation of PG synthesis [5-7]. Homologues of these hydrolases
can be found in several Proteobacteria classes, most of which are curved/helical, indicating that other bacteria
may also employ direct modification of the PG to achieve curvature and twist [5, 8, 9].
The main hypothesis that guides this proposal is that spatially localized PG hydrolases promote H. pylori
helical shape, which allows colonization of distinct niches from non-helical bacteria and underlies
persistent infection. Our collection of non-helical mutants provides unique opportunities to explore the
mechanisms of helical cell shape generation and maintenance in bacteria as well as the functional role(s) of cell
shape in niche acquisition and persistent colonization.
A more complete understanding of the causes and consequences of helical cell shape could elucidate
new therapeutic targets in H. pylori and other curved and helical pathogens, and will thus further the
mission of NIAID to unde...

## Key facts

- **NIH application ID:** 9928890
- **Project number:** 5R01AI136946-03
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Nina Salama
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $475,685
- **Award type:** 5
- **Project period:** 2018-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928890

## Citation

> US National Institutes of Health, RePORTER application 9928890, Mechanisms and consequence of helical shape generation in Helicobacter pylori (5R01AI136946-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9928890. Licensed CC0.

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