@article{678da283d67c4c929c7b37daa3e92e5f,
title = "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.",
author = "Liu, {Janet Z.} and Stefan Jellbauer and Poe, {Adam J.} and Vivian Ton and Michele Pesciaroli and Kehl-Fie, {Thomas E.} and Restrepo, {Nicole A.} and Hosking, {Martin P.} and Edwards, {Robert A.} and Andrea Battistoni and Paolo Pasquali and Lane, {Thomas E.} and Chazin, {Walter J.} and Thomas Vogl and Johannes Roth and Skaar, {Eric P.} and Manuela Raffatellu",
note = "Funding Information: We would like to acknowledge Sean-Paul Nuccio for help with editing the manuscript; Elizabeth Nolan for helpful discussions; Sebastian Winter and Andreas B{\"a}umler for the gift of plasmids; and Russell Gerards for his help with ICP-MS. This work was supported by National Institutes of Health Public Health Service Grants AI083619 and AI083663 and an IDSA ERF/NIFID Astellas Young Investigator Award (M.R.); National Institutes of Health Public Health Service Grants AI073843 (E.P.S.), GM62112-08S1 (W.J.C.), AI091771 (E.P.S. and W.J.C.), and NS041249 (T.E.L.); Istituto Superiore di Sanit{\`a} Intramural Research Project 11 US 24 and European Union Eranet-EMIDA project T99 (P.P. and A.B.); Interdisciplinary Center of Clinical Research, University of M{\"u}nster (Vo2/014/09 to T.V. and Ro2/004/10 to J.R.). J.Z.L. was partly supported by the NIH Immunology Research Training Grant T32 AI60573. ",
year = "2012",
month = mar,
day = "15",
doi = "10.1016/j.chom.2012.01.017",
language = "English (US)",
volume = "11",
pages = "227--239",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "3",
}