This is not a PBT2 paper, nor is it about otitis media (her main interest she publically told1 y ago) but it is about copper and streptococcus, one cause of otitis and a bacteria becoming more and often resistant to any antibiotic drug. Dr. McDevitt was the senior author of this paper. He is one of the 4 scientists who patented PBT2 as an antibiotic drug. I would think that this paper indicates that the research she promised is now giving her first publication in this respect.

Microbiol Spectr

. 2022 Dec 21;10(6):e0249522.

doi: 10.1128/spectrum.02495-22. Epub 2022 Nov 22.

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

Stephanie L Neville ¹, Bliss A Cunningham ¹, Eve A Maunders ¹, Aimee Tan ¹, Jacinta A Watts ¹, Katherine Ganio ¹, Bart A Eijkelkamp ², Victoria G Pederick ², Raquel Gonzalez de Vega ^{3 4}, David Clases ^{3 4}, Philip A Doble ³, Christopher A McDevitt ¹

Affiliations expand

• PMID: 36413018

PMCID: PMC9769658 DOI: 10.1128/spectrum.02495-22Free PMC article

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. IMPORTANCE Streptococcus pneumoniae (the pneumococcus) is one of the world's foremost bacterial pathogens. Treatment of both localized and systemic pneumococcal infection is becoming complicated by increasing rates of multidrug resistance globally. Copper is a potent antimicrobial agent used by the mammalian immune system in the defense against bacterial pathogens. However, unlike other bacterial species, this copper stress is unable to prosecute pneumococcal clearance. This study determines how the mammalian host inflicts copper stress on S. pneumoniae and the bacterial copper tolerance mechanisms that contribute to maintenance of viability and virulence in vitro and in vivo. This work has provided insight into the chemical biology of the host-pneumococcal interaction and identified a potential avenue for novel antimicrobial development.