# Mechanisms and consequence of helical shape generation in Helicobacter pylori

> **NIH NIH R01** · FRED HUTCHINSON CANCER CENTER · 2024 · $616,926

## Abstract

PROJECT SUMMARY
Bacteria come in many shapes, which may enhance motility, biofilm formation, nutrient uptake, and
pathogenesis. However, the 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, Caulobacter crescentus and Vibrio cholerae, curved rods, require fixed cell
spanning cytoskeletal proteins that bias PG synthesis to the opposite side of the cell to generate curvature.
Helicobacter pylori has emerged as a useful model to 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 fourth leading cause of cancer mortality. 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 curvature and bacterial infectivity that has now been extended to
other bacteria (Vibrio, Campylobacter). H. pylori’s strategy for maintaining helical shape differs significantly
from other studied bacteria. We showed that two distinct cytoskeletal proteins, MreB and the bactofilin CcmA,
promote higher relative rates of new cell wall incorporation at the major and minor helical axes, respectively,
and neither form cell spanning filaments. We found that CcmA requires the transmembrane protein Csd5 to
localize to the major helical axis and the Csd5-CcmA complex also contains the MurF PG precursor synthesis
enzyme, suggesting a possible mechanism for promoting PG synthesis. Our analyses of H. pylori morphology
during chronic infection revealed shape diversification (including changes in helical pitch and even loss of
helical curvature) that genetically maps to previously identified cell shape genes.
In this renewal application we propose to define mechanisms by which the Csd5-CcmA complex is localized
the major helical axis (Aim 1), define mechanisms of enhanced PG synthesis at the major and minor helical
axes and the role of spatially variation in relative PG synthesis rates and/or endopeptidase activity in
maintaining helical cell shape (Aim 2), and determine how cytoskeletal protein dynamics and natural sequence
polymorphisms modify helical pitch and stomach colonization (Aim3). A more complete understanding of the
mechanisms H. pylori uses to maintain and vary helical cell shape is needed to identify vulnerabilities that
could be targeted to augment current treatment regimens and to probe the mechanisms by which H. py...

## Key facts

- **NIH application ID:** 10904535
- **Project number:** 2R01AI136946-07
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Nina Salama
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $616,926
- **Award type:** 2
- **Project period:** 2018-06-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10904535

## Citation

> US National Institutes of Health, RePORTER application 10904535, Mechanisms and consequence of helical shape generation in Helicobacter pylori (2R01AI136946-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10904535. Licensed CC0.

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