# Role of cardiolipin in Helicobacter pylori flagellar biogenesis

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2022 · $302,000

## Abstract

PROJECT SUMMARY/ABSTRACT
 Helicobacter pylori colonizes the stomach of about half the human population worldwide and is the major
pathogenic factor for peptic ulcer disease and chronic gastritis, as well as a major risk factor for gastric cancer
and mucosa-associated lymphoid tissue lymphoma. H. pylori possess a cluster of polar flagella that the cell
uses for motility, which is required for host colonization. A membranous sheath surrounds the H. pylori flagellum,
a feature shared with other significant human pathogens, including pathogenic Vibrio species. Proposed
functions for the flagellar sheath include protection of the flagellar filament from gastric acid and adherence to
host cells. Nothing is known about the synthesis of the flagellar sheath in any bacterial species. Our preliminary
studies identified an enzyme (ClsC) responsible for synthesis of the glycerophospholipid cardiolipin (CL) in H.
pylori, and showed that clsC is required for flagellar biosynthesis in H. pylori G27. Highly purified H. pylori
sheathed flagella contain substantial amounts of CL, confirming a functional link between ClsC and the flagellar
sheath. These observations lead to our central hypothesis that CL is required for synthesis of the H. pylori
flagellar sheath, and lesions in CL synthesis inhibit flagellar biosynthesis in H. pylori G27. A comparative
genomics approach revealed a number of genes that are conserved in Helicobacter species that possess
sheathed flagella but are absent in Helicobacter species that lack a flagellar sheath. Some of these genes encode
an efflux system that our mutational analysis revealed to be required for flagellar biosynthesis in H. pylori G27.
The efflux system may form a unique cage-like structure that surrounds the flagellar motor as disrupting one of
the genes encoding the efflux system results in loss of the cage-like structure. These results led to our
hypothesis that the efflux system transports CL to the outer membrane for assembly into the flagellar sheath.
To understand the link between CL and biosynthesis of the H. pylori flagellar sheath, three Specific Aims will be
pursued: (1) To define the role of CL in H. pylori flagellum biogenesis. (2) To determine if the efflux system is a
CL transporter involved in flagellar sheath biosynthesis. (3) To determine if CL or the efflux system are required
for localization of proteins to the flagellar sheath. The proposed research will address a critical gap in our
knowledge of the biosynthesis of the H. pylori sheathed flagellum, as well as provide a paradigm for flagellar
sheath biosynthesis in other medically relevant bacteria. The research will also have a broad impact on our
knowledge of glycerophospholipid trafficking in the bacterial cell envelope.

## Key facts

- **NIH application ID:** 10329976
- **Project number:** 5R01AI140444-04
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Timothy Randall Hoover
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $302,000
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10329976

## Citation

> US National Institutes of Health, RePORTER application 10329976, Role of cardiolipin in Helicobacter pylori flagellar biogenesis (5R01AI140444-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10329976. Licensed CC0.

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