Zinc Sequestration by the Neutrophil Protein Calprotectin Enhances Salmonella Growth in the Inflamed Gut
| Autor: | Michele Pesciaroli, Nicole A. Restrepo, Walter J. Chazin, Thomas E. Kehl-Fie, Thomas Vogl, Andrea Battistoni, Vivian Ton, Thomas E. Lane, Johannes Roth, Eric P. Skaar, Adam J. Poe, Stefan Jellbauer, Robert Edwards, Janet Z. Liu, Paolo Pasquali, Martin P. Hosking, Manuela Raffatellu |
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| Rok vydání: | 2012 |
| Předmět: |
Salmonella typhimurium
Cancer Research Salmonella Transcription Genetic Neutrophils Inbred C57BL medicine.disease_cause Mice Feces fluids and secretions Innate Cecum Pathogen Mice Knockout 0303 health sciences Leukocyte L1 Antigen Complex Antimicrobial Zinc Host-Pathogen Interactions Salmonella Infections medicine.symptom Transcription Protein Binding Animals Diarrhea Immunity Innate Inflammation Bacterial Proteins Mice Inbred C57BL ATP-Binding Cassette Transporters Salmonella Infections Animal Knockout Biology Microbiology 03 medical and health sciences Genetic Immunity Immunology and Microbiology(all) Virology medicine Settore BIO/10 Molecular Biology 030304 developmental biology Innate immune system Animal 030306 microbiology Parasitology Calprotectin |
| Zdroj: | Cell Host & Microbe. 11:227-239 |
| ISSN: | 1931-3128 |
| Popis: | SummaryNeutrophils are innate immune cells that counter pathogens by many mechanisms, including release of antimicrobial proteins such as calprotectin to inhibit bacterial growth. Calprotectin sequesters essential micronutrient metals such as zinc, thereby limiting their availability to microbes, a process termed nutritional immunity. We find that while calprotectin is induced by neutrophils during infection with the gut pathogen Salmonella Typhimurium, calprotectin-mediated metal sequestration does not inhibit S. Typhimurium proliferation. Remarkably, S. Typhimurium overcomes calprotectin-mediated zinc chelation by expressing a high affinity zinc transporter (ZnuABC). A S. Typhimurium znuA mutant impaired for growth in the inflamed gut was rescued in the absence of calprotectin. ZnuABC was also required to promote the growth of S. Typhimurium over that of competing commensal bacteria. Thus, our findings indicate that Salmonella thrives in the inflamed gut by overcoming the zinc sequestration of calprotectin and highlight the importance of zinc acquisition in bacterial intestinal colonization. |
| Databáze: | OpenAIRE |
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