Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens

Sci Rep. 2019 Sep 25;9(1):13851. doi: 10.1038/s41598-019-50027-0.


The nickel (Ni)-specific chelator dimethylglyoxime (DMG) has been used for many years to detect, quantitate or decrease Ni levels in various environments. Addition of DMG at millimolar levels has a bacteriostatic effect on some enteric pathogens, including multidrug resistant (MDR) strains of Salmonella Typhimurium and Klebsiella pneumoniae. DMG inhibited activity of two Ni-containing enzymes, Salmonella hydrogenase and Klebsiella urease. Oral delivery of nontoxic levels of DMG to mice previously inoculated with S. Typhimurium led to a 50% survival rate, while 100% of infected mice in the no-DMG control group succumbed to salmonellosis. Pathogen colonization numbers from livers and spleens of mice were 10- fold reduced by DMG treatment of the Salmonella-infected mice. Using Nuclear Magnetic Resonance, we were able to detect DMG in the livers of DMG-(orally) treated mice. Inoculation of Galleria mellonella (wax moth) larvae with DMG prior to injection of either MDR K. pneumoniae or MDR S. Typhimurium led to 40% and 60% survival, respectively, compared to 100% mortality of larvae infected with either pathogen, but without prior DMG administration. Our results suggest that DMG-mediated Ni-chelation could provide a novel approach to combat enteric pathogens, including recalcitrant multi-drug resistant strains.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Chelation Therapy / methods*
  • Drug Resistance, Multiple, Bacterial / drug effects
  • Female
  • Gastrointestinal Microbiome / drug effects
  • Mice
  • Microbial Sensitivity Tests
  • Moths / drug effects
  • Moths / microbiology*
  • Nickel / chemistry
  • Oximes / administration & dosage*
  • Oximes / pharmacology
  • Salmonella Infections, Animal / drug therapy*
  • Salmonella Infections, Animal / mortality
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / pathogenicity*
  • Survival Rate
  • Treatment Outcome


  • Oximes
  • dimethylglyoxime
  • Nickel