Efficient gastrointestinal colonization by Campylobacter jejuni requires components of the ChuABCD heme transport system

Vincent R. Randaisi; Madison L. Bunch; Will N. Beavers; Theresa Rogers; Ryan Mesler; Tiara D. Ashurst; Dallas R. Donohoe; Andrew J. Monteith; Jeremiah G. Johnson

doi:10.1101/2025.03.18.643992

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Efficient gastrointestinal colonization by Campylobacter jejuni requires components of the ChuABCD heme transport system

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Efficient gastrointestinal colonization by Campylobacter jejuni requires components of the ChuABCD heme transport system

Vincent R. Randaisi, Madison L. Bunch, Will N. Beavers, Theresa Rogers, Ryan Mesler, Tiara D. Ashurst, Dallas R. Donohoe, Andrew J. Monteith and Jeremiah G. Johnson

bioRxiv

Cold Spring Harbor Laboratory, 1.1

03/19/2025

DOI: 10.1101/2025.03.18.643992

PMCID: PMC11957022

PMID: 40166214

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https://doi.org/10.1101/2025.03.18.643992View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Previous research demonstrated that Campylobacter jejuni encodes a heme utilization system that facilitates heme-dependent growth under iron-limiting conditions and that transcription of this system is induced during human infection. Despite these observations, it remained unknown whether the heme transport system is required for colonization and disease in a susceptible host. To address this, we created individual non-polar deletion mutants of each component of the heme transport system, as well as a total deletion of the inner membrane transporter, ChuBCD, and examined their ability to promote heme-dependent growth and iron uptake. From this work, we found that only the heme receptor, ChuA, was required for heme-dependent growth and iron acquisition, which supports earlier work of another group. Further, we examined whether intestinal colonization, immune activation, and pathology were altered during infection with these mutants. After establishing that elevated heme and chuABCD expression occurs during C. jejuni infection of IL-10-/- mice, we found that heme transport mutants exhibited significantly reduced fecal shedding and colonization of the cecum and colon. In addition, we found that neutrophil and macrophage recruitment and intestinal pathology often remained intermediately elevated despite decreased bacterial loads. These results suggest that heme utilization promotes efficient colonization and full pathogenicity in C. jejuni, but that neither is completely abrogated in its absence.

Microbiology

Details

Title: Subtitle: Efficient gastrointestinal colonization by Campylobacter jejuni requires components of the ChuABCD heme transport system
Creators: Vincent R. Randaisi - University of Tennessee at Knoxville
Madison L. Bunch - University of Iowa
Will N. Beavers - Louisiana State University
Theresa Rogers - University of Tennessee at Knoxville
Ryan Mesler
Tiara D. Ashurst - University of Tennessee at Knoxville
Dallas R. Donohoe - University of Tennessee at Knoxville
Andrew J. Monteith - University of Tennessee at Knoxville
Jeremiah G. Johnson - The University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv
Edition: 1.1
DOI: 10.1101/2025.03.18.643992
PMID: 40166214
PMCID: PMC11957022
NLM abbreviation: bioRxiv
ISSN: 2692-8205
eISSN: 2692-8205
Publisher: Cold Spring Harbor Laboratory
Number of pages: 29
Language: English
Date posted: 03/19/2025
Academic Unit: Microbiology and Immunology
Record Identifier: 9984805004102771

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