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

Liu JZ, Jellbauer S, Poe AJ, Ton V, Pesciaroli M, Kehl-Fie TE, Restrepo NA, Hosking MP, Edwards RA, Battistoni A, Pasquali P, Lane TE, Chazin WJ, Vogl T, Roth J, Skaar EP, Raffatellu M
Cell Host Microbe. 2012 11 (3): 227-39

PMID: 22423963 · PMCID: PMC3308348 · DOI:10.1016/j.chom.2012.01.017

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.

Copyright © 2012 Elsevier Inc. All rights reserved.

MeSH Terms (19)

Animals ATP-Binding Cassette Transporters Bacterial Proteins Cecum Diarrhea Feces Host-Pathogen Interactions Immunity, Innate Inflammation Leukocyte L1 Antigen Complex Mice Mice, Inbred C57BL Mice, Knockout Neutrophils Protein Binding Salmonella Infections, Animal Salmonella typhimurium Transcription, Genetic Zinc

Connections (2)

This publication is referenced by other Labnodes entities: