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

ABSTRACT: 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.

SUBMITTER: Benoit SL

PROVIDER: S-EPMC6761267 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Benoit Stéphane L SL Schmalstig Alan A AA Glushka John J Maier Susan E SE Edison Arthur S AS Maier Robert J RJ

Scientific reports 20190925 1

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 previousl ...[more]

PMID: 31554822

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

Publications

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

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