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

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

Research output: Contribution to journalArticlepeer-review

15 Downloads (Pure)

Abstract

Metal ions are required by all organisms for the chemical processes that support life. However, in excess they can also exert toxicity within biological systems. During infection, bacterial pathogens such as Streptococcus pneumoniae are exposed to host-imposed metal intoxication, where the toxic properties of metals, such as copper, are exploited to aid in microbial clearance. However, previous studies investigating the antimicrobial efficacy of copper in vivo have reported variable findings. Here, we use a highly copper-sensitive strain of S. pneumoniae, lacking both copper efflux and intracellular copper buffering by glutathione, to investigate how copper stress is managed and where it is encountered during infection. We show that this strain exhibits highly dysregulated copper homeostasis, leading to the attenuation of growth and hyperaccumulation of copper in vitro. In a murine infection model, whole-tissue copper quantitation and elemental bioimaging of the murine lung revealed that infection with S. pneumoniae resulted in increased copper abundance in specific tissues, with the formation of spatially discrete copper hot spots throughout the lung. While the increased copper was able to reduce the viability of the highly copper-sensitive strain in a pneumonia model, copper levels in professional phagocytes and in a bacteremic model were insufficient to prosecute bacterial clearance. Collectively, this study reveals that host copper is redistributed to sites of infection and can impact bacterial viability in a hypersusceptible strain. However, in wild-type S. pneumoniae, the concerted actions of the copper homeostatic mechanisms are sufficient to facilitate continued viability and virulence of the pathogen.

Original languageEnglish
Number of pages17
JournalMicrobiology Spectrum
Volume10
Issue number6
DOIs
Publication statusPublished - 22 Nov 2022
Externally publishedYes

Keywords

  • antimicrobial
  • antimicrobial activity
  • copper tolerance
  • glutathione
  • metal intoxication
  • murine infection
  • Streptococcus pneumoniae

Fingerprint

Dive into the research topics of 'Host-Mediated Copper Stress Is Not Protective against Streptococcus pneumoniae D39 Infection'. Together they form a unique fingerprint.

Cite this