Host subversion of bacterial metallophore usage drives copper intoxication
Saika Hossain1, Jacqueline R Morey1, Stephanie L Neville2
1Department of Microbiology, University of Illinois at Urbana-Champaign , Urbana, Illinois, USA.
Mbio
|September 22, 2023
Summary
Host zinc starvation response makes Staphylococcus aureus vulnerable to copper toxicity. Bacteria using staphylopine metallophores can be exploited by hosts to deliver toxic copper loads, a conserved vulnerability in pathogens.
Area of Science:
- Microbiology
- Infectious Diseases
- Bacterial Pathogenesis
Background:
- Bacteria face challenges of metal starvation and intoxication during infection.
- Staphylococcus aureus employs the metallophore staphylopine to manage zinc starvation.
- Host immune responses can manipulate bacterial metal homeostasis.
Purpose of the Study:
- To investigate how host zinc-withholding strategies impact Staphylococcus aureus.
- To explore the role of staphylopine in bacterial susceptibility to metal intoxication.
- To determine if host-mediated copper intoxication of S. aureus is a viable infection control strategy.
Main Methods:
- Utilized bacterial culture models under varying metal concentrations.
- Analyzed staphylopine production and function in S. aureus.
- Assessed bacterial survival and toxicity in the presence of host-derived metals.
Main Results:
- Host zinc starvation sensitizes S. aureus to copper intoxication.
- Staphylopine's promiscuous metal binding is leveraged by the host to deliver toxic copper.
- This mechanism represents a conserved vulnerability exploitable by hosts against pathogens.
Conclusions:
- The host can weaponize bacterial metallophores like staphylopine for pathogen control.
- This challenges the notion that broad-spectrum metal binding by metallophores is always advantageous for bacteria.
- Targeting metallophore-mediated metal transport offers a potential therapeutic avenue against bacterial infections.
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