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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)227-239
Number of pages13
JournalCell Host and Microbe
Volume11
Issue number3
DOIs
StatePublished - Mar 15 2012

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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  • Cite this

    Liu, J. Z., Jellbauer, S., Poe, A. J., Ton, V., Pesciaroli, M., Kehl-Fie, T. E., Restrepo, N. A., Hosking, M. P., Edwards, R. A., Battistoni, A., Pasquali, P., Lane, T. E., Chazin, W. J., Vogl, T., Roth, J., Skaar, E. P., & Raffatellu, M. (2012). Zinc sequestration by the neutrophil protein calprotectin enhances salmonella growth in the inflamed gut. Cell Host and Microbe, 11(3), 227-239. https://doi.org/10.1016/j.chom.2012.01.017