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.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of California, Irvine, CA 92697, USA.
authors.forename: Janet Z
authors.initials: JZ
authors.lastname: Liu
authors.forename: Stefan
authors.initials: S
authors.lastname: Jellbauer
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Poe
authors.forename: Vivian
authors.initials: V
authors.lastname: Ton
authors.forename: Michele
authors.initials: M
authors.lastname: Pesciaroli
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Kehl-Fie
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Restrepo
authors.forename: Martin P
authors.initials: MP
authors.lastname: Hosking
authors.forename: Robert A
authors.initials: RA
authors.lastname: Edwards
authors.forename: Andrea
authors.initials: A
authors.lastname: Battistoni
authors.forename: Paolo
authors.initials: P
authors.lastname: Pasquali
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Lane
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Chazin
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogl
authors.forename: Johannes
authors.initials: J
authors.lastname: Roth
authors.forename: Eric P
authors.initials: EP
authors.lastname: Skaar
authors.forename: Manuela
authors.initials: M
authors.lastname: Raffatellu
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002432:Cecum / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D003967:Diarrhea / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D039841:Leukocyte L1 Antigen Complex / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism*; D011485:Protein Binding; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012486:Salmonella typhimurium / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D015032:Zinc / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D039841:Leukocyte L1 Antigen Complex; D015032:Zinc