دورية أكاديمية
Host-Mediated Copper Stress Is Not Protective against Streptococcus pneumoniae D39 Infection.
العنوان: | Host-Mediated Copper Stress Is Not Protective against Streptococcus pneumoniae D39 Infection. |
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المؤلفون: | Neville SL; Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbournegrid.1008.9, Melbourne, Victoria, Australia., Cunningham BA; Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbournegrid.1008.9, Melbourne, Victoria, Australia., Maunders EA; Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbournegrid.1008.9, Melbourne, Victoria, Australia., Tan A; Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbournegrid.1008.9, Melbourne, Victoria, Australia., Watts JA; Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbournegrid.1008.9, Melbourne, Victoria, Australia., Ganio K; Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbournegrid.1008.9, Melbourne, Victoria, Australia., Eijkelkamp BA; Department of Molecular and Biomedical Science, School of Biological Sciences, University of Adelaidegrid.1010.0, Adelaide, South Australia, Australia., Pederick VG; Department of Molecular and Biomedical Science, School of Biological Sciences, University of Adelaidegrid.1010.0, Adelaide, South Australia, Australia., Gonzalez de Vega R; The Atomic Medicine Initiative, University of Technology, Broadway, Sydney, New South Wales, Australia.; Institute of Chemistry, University of Grazgrid.5110.5, Graz, Austria., Clases D; The Atomic Medicine Initiative, University of Technology, Broadway, Sydney, New South Wales, Australia.; Institute of Chemistry, University of Grazgrid.5110.5, Graz, Austria., Doble PA; The Atomic Medicine Initiative, University of Technology, Broadway, Sydney, New South Wales, Australia., McDevitt CA; Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbournegrid.1008.9, Melbourne, Victoria, Australia. |
المصدر: | Microbiology spectrum [Microbiol Spectr] 2022 Dec 21; Vol. 10 (6), pp. e0249522. Date of Electronic Publication: 2022 Nov 22. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: ASM Press Country of Publication: United States NLM ID: 101634614 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2165-0497 (Electronic) Linking ISSN: 21650497 NLM ISO Abbreviation: Microbiol Spectr Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Washington, DC : ASM Press, 2013- |
مواضيع طبية MeSH: | Anti-Infective Agents* , Pneumococcal Infections*/microbiology, Animals ; Mice ; Bacterial Proteins ; Copper ; Lung/microbiology ; Streptococcus pneumoniae |
مستخلص: | 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. |
فهرسة مساهمة: | Keywords: Streptococcus pneumoniae; antimicrobial; antimicrobial activity; copper tolerance; glutathione; metal intoxication; murine infection |
المشرفين على المادة: | 0 (Anti-Infective Agents) 0 (Bacterial Proteins) 789U1901C5 (Copper) |
تواريخ الأحداث: | Date Created: 20221122 Date Completed: 20230105 Latest Revision: 20230105 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC9769658 |
DOI: | 10.1128/spectrum.02495-22 |
PMID: | 36413018 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2165-0497 |
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DOI: | 10.1128/spectrum.02495-22 |