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...

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Autores principales:	Stéphane L. Benoit, Alan A. Schmalstig, John Glushka, Susan E. Maier, Arthur S. Edison, Robert J. Maier
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ba948ee605c447938767fdd68a6d105c
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spelling	oai:doaj.org-article:ba948ee605c447938767fdd68a6d105c2021-12-02T15:10:03ZNickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens10.1038/s41598-019-50027-02045-2322https://doaj.org/article/ba948ee605c447938767fdd68a6d105c2019-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-50027-0https://doaj.org/toc/2045-2322Abstract 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.Stéphane L. BenoitAlan A. SchmalstigJohn GlushkaSusan E. MaierArthur S. EdisonRobert J. MaierNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stéphane L. Benoit Alan A. Schmalstig John Glushka Susan E. Maier Arthur S. Edison Robert J. Maier Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens
description	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.
format	article
author	Stéphane L. Benoit Alan A. Schmalstig John Glushka Susan E. Maier Arthur S. Edison Robert J. Maier
author_facet	Stéphane L. Benoit Alan A. Schmalstig John Glushka Susan E. Maier Arthur S. Edison Robert J. Maier
author_sort	Stéphane L. Benoit
title	Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens
title_short	Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens
title_full	Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens
title_fullStr	Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens
title_full_unstemmed	Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens
title_sort	nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/ba948ee605c447938767fdd68a6d105c
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Nickel chelation therapy as an approach to combat multi-drug resistant enteric pathogens

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