Siderophore-based immunization strategy to inhibit growth of enteric pathogens
Open accessAbstract
Infections with Gram-negative pathogens pose a serious threat to public health. This scenario is exacerbated by increases in antibiotic resistance and the limited availability of vaccines and therapeutic tools to combat these infections. Here, we report an immunization approach that targets siderophores, which are small molecules exported by enteric Gram-negative pathogens to acquire iron, an essential nutrient, in the host. Because siderophores are nonimmunogenic, we designed and synthesized conjugates of a native siderophore and the immunogenic carrier protein cholera toxin subunit B (CTB). Mice immunized with the CTB-siderophore conjugate developed anti-siderophore antibodies in the gut mucosa, and when mice were infected with the enteric pathogen Salmonella, they exhibited reduced intestinal colonization and reduced systemic dissemination of the pathogen. Moreover, analysis of the gut microbiota revealed that reduction of Salmonella colonization in the inflamed gut was accompanied by expansion of Lactobacillus spp., which are beneficial commensal organisms that thrive in similar locales as Enterobacteriaceae. Collectively, our results demonstrate that anti-siderophore antibodies inhibit Salmonella colonization. Because siderophore-mediated iron acquisition is a virulence trait shared by many bacterial and fungal pathogens, blocking microbial iron acquisition by siderophore-based immunization or other siderophore-targeted approaches may represent a novel strategy to prevent and ameliorate a broad range of infections.
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Salmonella has both siderophore-dependent and -independent strategies to acquire iron from the host.
“Salmonella has both siderophore-dependent and -independent strategies to acquire iron from the host (14).”
From Dopamine Is a Siderophore-Like Iron Chelator That Promotes <i>Salmonella enterica</i> Serovar Typhimurium Virulence in Mice (2019) · cites this paper as [14]
Immunization against enterobactins supported, rather than undermined, the non-pathogenic role of commensal microbiota.
“Importantly, this approach supported, rather than undermined, the non‐pathogenic role of commensal microbiota. 174”
From The battle for iron in enteric infections (2020) · cites this paper as [174]
Improving host nutritional immunity through immunization against enterobactins reduced the severity of experimental gastrointestinal Salmonella infection, systemic dissemination and infection-associated dysbiosis.
“Improving host nutritional immunity through immunization against enterobactins reduced the severity of experimental gastrointestinal Salmonella infection, systemic dissemination and infection‐associated dysbiosis.”
From The battle for iron in enteric infections (2020) · cites this paper as [174]
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- Authors
- Sassone-Corsi, M., Chairatana, P., Zheng, T., Perez-Lopez, A., Edwards, R. A., George, M. D., Nolan, E. M., & Raffatellu, M.
- Affiliations
- Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, CA 92697;
- Massachusetts Institute of Technology (US)
- University of California, Irvine (US)
- University of California, Davis (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-11-07
- Volume
- 113
- Issue
- 47
- Pages
- 13462-13467
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5127304
- OpenAlex
- W2556896730
- Cited by
- 75
- References
- 49
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 9 · 2023: 8 · 2022: 4 · 2021: 9 · 2020: 10 · 2019: 8 · 2018: 9 · 2017: 8
- FWCI
- 8.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- HHS | NIH | National Institute of Allergy and Infectious Diseases (U54AI065359, AI101784, AI114625)
- Burroughs Wellcome Fund (N/A)
- University of California Institute for Mexico and the United States (N/A)
- Kinship Foundation (N/A)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
- Life Sciences › Agricultural and Biological Sciences › Food Science › Salmonella and Campylobacter epidemiology
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Keywords
- cholera toxin B subunit, Salmonella, iron acquisition, intestinal mucosa, intestinal colonization, gut microbiota, Lactobacillus, commensal bacteria, antibiotic resistance
- MeSH terms
- Gastrointestinal Microbiome, Animals, Antibody Formation, Enterobacteriaceae, Female, Immunization, Inflammation, Mice, Inbred C57BL, Colony Count, Microbial, Siderophores, Immunity, Mucosal
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