Zinc sequestration by the neutrophil protein calprotectin enhances Salmonella growth in the inflamed gut.

Abstract

Neutrophils 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.

• Authors: Janet Z Liu, Stefan Jellbauer, Adam J Poe, Vivian Ton, Michele Pesciaroli, Thomas E Kehl-Fie, Nicole A Restrepo, Martin P Hosking, Robert A Edwards, Andrea Battistoni, Paolo Pasquali, Thomas E Lane, Walter J Chazin, Thomas Vogl, Johannes Roth, Eric P Skaar, Manuela Raffatellu
• Journal: Cell host & microbe (Cell Host Microbe) Vol. 11 Issue 3 Pg. 227-39 (Mar 15 2012) ISSN: 1934-6069 [Electronic] United States
• PMID: 22423963 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• ATP-Binding Cassette Transporters
• Bacterial Proteins
• Leukocyte L1 Antigen Complex
• Zinc

Topics

• ATP-Binding Cassette Transporters (genetics, metabolism)
• Animals
• Bacterial Proteins (genetics, metabolism)
• Cecum (metabolism, microbiology, pathology)
• Diarrhea (immunology, metabolism, microbiology)
• Feces (chemistry, microbiology)
• Host-Pathogen Interactions
• Immunity, Innate
• Inflammation (immunology, metabolism, microbiology)
• Leukocyte L1 Antigen Complex (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neutrophils (metabolism)
• Protein Binding
• Salmonella Infections, Animal (immunology, metabolism, pathology)
• Salmonella typhimurium (growth & development, metabolism, physiology)
• Transcription, Genetic
• Zinc (metabolism)