Host-Mediated Copper Stress Is Not Protective against Streptococcus pneumoniae D39 Infection

Neville, Stephanie L.; Cunningham, Bliss A.; Maunders, Eve A.; Tan, Aimee; Watts, Jacinta A.; Ganio, Katherine; Eijkelkamp, Bart A.; Pederick, Victoria G.; Vega, Raquel González de; Clases, David; Doble, Philip; McDevitt, Christopher A.

doi:10.1128/spectrum.02495-22

Cited by 5 publications

(1 citation statement)

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“…Further work revealed that StP and the Cnt importer enable Cu to gain access to the bacterial cytoplasm, and that import via this transporter can overwhelm the Cu detoxification machinery. A recent study revealed that during infection, Cu abundance increases ~150-fold in Zn-depleted regions of tissue 38 . This leads to a model (Fig.…”

Section: Discussionmentioning

confidence: 99%

Host subversion of bacterial metallophore usage drives copper intoxication

Hossain

Morey

Neville

et al. 2023

Preprint

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Microorganisms can acquire metal ions in metal-limited environments using small molecules called metallophores. While metals and their importers are essential, metals can also be toxic, and metallophores have limited ability to discriminate metals. The impact of the metallophore-mediated non-cognate metal uptake on bacterial metal homeostasis and pathogenesis remains to be defined. The globally significant pathogen Staphylococcus aureus uses the Cnt system to secrete the metallophore staphylopine in zinc-limited host niches. Here, we show that staphylopine and the Cnt system facilitate bacterial copper uptake, potentiating the need for copper detoxification. During in vivo infection, staphylopine usage increased S. aureus susceptibility to host-mediated copper stress, indicating that the innate immune response can harness the antimicrobial potential of altered elemental abundances in host niches. Collectively, these observations show that while the broad-spectrum metal-chelating properties of metallophores can be advantageous, the host can exploit these properties to drive metal intoxication and mediate antibacterial control.

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Section: Discussionmentioning

confidence: 99%