Dopamine Is a Siderophore-Like Iron Chelator That Promotes Salmonella enterica Serovar Typhimurium Virulence in Mice.
Dichtl S, Demetz E, Haschka D, Tymoszuk P, Petzer V, Nairz M, Seifert M, Hoffmann A, Brigo N, Würzner R, Theurl I, Karlinsey JE, Fang FC, Weiss G
MBio. Feb 2019
COMMENT: This work can have an important impact in septic shock produced by Salmonella since it reports that dopamine, used in septic shock treatment, promotes Salmonella virulence because acts as siderophore-like iron chelator that stimulates bacterial proliferation. These findings can avoid the detrimental effect of dopamine in septic shock patients and provide data to design new antimicrobial therapy approaches based on the inhibition of iron acquisition bacterial systems.
To study whether dopamine administration impacts the course of Salmonella infections, especially in sepsis.
The authors demonstrate that Dopamine:
- Promotes Salmonella Typhimurium growth in vitro
- Worsens the outcome of Salmonella Typhimurium infection in vivo
- Influences iron homeostasis during Salmonella Typhimurium infection in vivo
Specifically, we found that DA increases iron acquisition by S. Typhimurium, which leads to enhanced proliferation, higher bacterial numbers in tissues, and significantly reduced survival of infected mice. The effects of DA on bacterial proliferation are abrogated by mutation of the Salmonella entC, sit, and feo genes, which encode important iron uptake systems, indicating that iron is involved in DA stimulation of bacterial proliferation.
The stimulation of iron acquisition by DA may reflect a combination of pseudosiderophore-mediated iron delivery and altered expression of iron transport genes, in particular the SitABCD system.
Salmonella displays one of the most serious infectious disease threats for human health. Our findings suggest that the use of DA as a vasoactive drug in patients with septic shock due to infection with intracellular pathogens such as Salmonella might have adventitious effects on iron homeostasis and bacterial growth that are detrimental to the host. On the other hand, our observations suggest that interventions to limit microbial iron access represent a promising strategy for the treatment of infection.