The Regulatory Protein ChuP Connects Heme and Siderophore-Mediated Iron Acquisition Systems Required for Chromobacterium violaceum Virulence
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Abstract
Chromobacterium violaceum is an environmental Gram-negative beta-proteobacterium that causes systemic infections in humans. C. violaceum uses siderophore-based iron acquisition systems to overcome the host-imposed iron limitation, but its capacity to use other iron sources is unknown. In this work, we characterized ChuPRSTUV as a heme utilization system employed by C. violaceum to explore an important iron reservoir in mammalian hosts, free heme and hemoproteins. We demonstrate that the chuPRSTUV genes comprise a Fur-repressed operon that is expressed under iron limitation. The chu operon potentially encodes a small regulatory protein (ChuP), an outer membrane TonB-dependent receptor (ChuR), a heme degradation enzyme (ChuS), and an inner membrane ABC transporter (ChuTUV). Our nutrition growth experiments using C. violaceum chu deletion mutants revealed that, with the exception of chuS , all genes of the chu operon are required for heme and hemoglobin utilization in C. violaceum . The mutant strains without chuP displayed increased siderophore halos on CAS plate assays. Significantly, we demonstrate that ChuP connects heme and siderophore utilization by acting as a positive regulator of chuR and vbuA , which encode the TonB-dependent receptors for the uptake of heme (ChuR) and the siderophore viobactin (VbuA). Our data favor a model of ChuP as a heme-binding post-transcriptional regulator. Moreover, our virulence data in a mice model of acute infection demonstrate that C. violaceum uses both heme and siderophore for iron acquisition during infection, with a preference for siderophores over the Chu heme utilization system.
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Flagged first, then by citations
- Authors
- de Lima, V. M., Batista, B. B., & da Silva Neto, J. F.
- Affiliations
- Universidade de São Paulo (BR)
- ORCID
- Batista, Bianca B.
- Venue
- Frontiers in Cellular and Infection Microbiology
- Publisher
- Frontiers Media SA
- Published
- 2022-05-11
- Volume
- 12
- Pages
- 873536-873536
- ISSN
- 2235-2988 (ISSN-L)
- PMC
- PMC9131926
- OpenAlex
- W4280565033
- Cited by
- 17
- References
- 18
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 7 · 2023: 5
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Cellular and Infection Microbiology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo (2018/01388-6 , 2020/00259-8)
- Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Infections and bacterial resistance
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Enterobacteriaceae and Cronobacter Research
- Keywords
- Chromobacterium violaceum, heme utilization, siderophore-mediated iron acquisition, TonB-dependent receptors, post-transcriptional regulation, heme degradation, ABC transporters, virulence, acute infection, hemoglobin utilization
- MeSH terms
- Animals, Chromobacterium, Heme, Iron, Mammals, Transcription Factors, Virulence, Siderophores, Mice
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