Salmonella Mitigates Oxidative Stress and Thrives in the Inflamed Gut by Evading Calprotectin-Mediated Manganese Sequestration

Cell Host Microbe. 2016 Jun 8;19(6):814-25. doi: 10.1016/j.chom.2016.05.005.


Neutrophils hinder bacterial growth by a variety of antimicrobial mechanisms, including the production of reactive oxygen species and the secretion of proteins that sequester nutrients essential to microbes. A major player in this process is calprotectin, a host protein that exerts antimicrobial activity by chelating zinc and manganese. Here we show that the intestinal pathogen Salmonella enterica serovar Typhimurium uses specialized metal transporters to evade calprotectin sequestration of manganese, allowing the bacteria to outcompete commensals and thrive in the inflamed gut. The pathogen's ability to acquire manganese in turn promotes function of SodA and KatN, enzymes that use the metal as a cofactor to detoxify reactive oxygen species. This manganese-dependent SodA activity allows the bacteria to evade neutrophil killing mediated by calprotectin and reactive oxygen species. Thus, manganese acquisition enables S. Typhimurium to overcome host antimicrobial defenses and support its competitive growth in the intestine.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Antioxidants / metabolism
  • Bacterial Proteins / metabolism
  • Chelating Agents / pharmacology
  • Escherichia coli / growth & development
  • Escherichia coli / physiology
  • Gastroenteritis / drug therapy
  • Gastroenteritis / metabolism
  • Gastroenteritis / microbiology*
  • Intestinal Mucosa / metabolism
  • Intestines / microbiology*
  • Leukocyte L1 Antigen Complex / pharmacology*
  • Manganese / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Neutrophils / metabolism
  • Oxidative Stress / physiology*
  • Reactive Oxygen Species / metabolism
  • Salmonella Infections / drug therapy
  • Salmonella Infections / metabolism
  • Salmonella Infections / microbiology
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / enzymology
  • Salmonella typhimurium / growth & development
  • Salmonella typhimurium / physiology*
  • Symbiosis
  • Zinc / metabolism


  • Anti-Bacterial Agents
  • Antioxidants
  • Bacterial Proteins
  • Chelating Agents
  • Leukocyte L1 Antigen Complex
  • Reactive Oxygen Species
  • Manganese
  • Zinc