Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

The cyclic nitroxide antioxidant 4-methoxy-TEMPO decreases mycobacterial burden in vivo through host and bacterial targets

Harrison D Black, Wenbo Xu, Elinor Hortle, Sonia I Roberston, Warwick J Britton, Amandeep Kaur, Elizabeth J New, Paul K Witting, Belal Chami, Stefan H Oehlers
doi: https://doi.org/10.1101/464586
Harrison D Black
aCentenary Institute, The University of Sydney, Australia.
bDiscipline of Pathology Faculty of Medicine and Health, The University of Sydney, Australia.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wenbo Xu
aCentenary Institute, The University of Sydney, Australia.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elinor Hortle
aCentenary Institute, The University of Sydney, Australia.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sonia I Roberston
aCentenary Institute, The University of Sydney, Australia.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Warwick J Britton
aCentenary Institute, The University of Sydney, Australia.
cCentral Clinical School Faculty of Medicine and Health, The University of Sydney, Australia.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Amandeep Kaur
dSchool of Chemistry, The University of Sydney, Australia.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elizabeth J New
dSchool of Chemistry, The University of Sydney, Australia.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paul K Witting
bDiscipline of Pathology Faculty of Medicine and Health, The University of Sydney, Australia.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Belal Chami
bDiscipline of Pathology Faculty of Medicine and Health, The University of Sydney, Australia.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stefan H Oehlers
aCentenary Institute, The University of Sydney, Australia.
cCentral Clinical School Faculty of Medicine and Health, The University of Sydney, Australia.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: stefan.oehlers@sydney.edu.au
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Tuberculosis is a chronic inflammatory disease caused by persistent infection with Mycobacterium tuberculosis. The rise of antibiotic resistant strains necessitates the design of novel treatments. Recent evidence shows that not only is M. tuberculosis highly resistant to oxidative killing, it also co-opts host oxidant production to induce phagocyte death facilitating bacterial dissemination. We have targeted this redox environment with the cyclic nitroxide derivative 4-methoxy-TEMPO (MetT) in the zebrafish-M. marinum infection model. MetT inhibited the production of mitochondrial ROS and decreased infection-induced cell death to aid containment of infection. We identify a second mechanism of action whereby stress conditions, including hypoxia, found in the infection microenvironment appear to sensitise M. marinum to killing by MetT both in vitro and in vivo. Together, our study demonstrates MetT inhibited the growth and dissemination of M. marinum through host and bacterial targets.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
Back to top
PreviousNext
Posted November 11, 2018.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
The cyclic nitroxide antioxidant 4-methoxy-TEMPO decreases mycobacterial burden in vivo through host and bacterial targets
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
The cyclic nitroxide antioxidant 4-methoxy-TEMPO decreases mycobacterial burden in vivo through host and bacterial targets
Harrison D Black, Wenbo Xu, Elinor Hortle, Sonia I Roberston, Warwick J Britton, Amandeep Kaur, Elizabeth J New, Paul K Witting, Belal Chami, Stefan H Oehlers
bioRxiv 464586; doi: https://doi.org/10.1101/464586
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
The cyclic nitroxide antioxidant 4-methoxy-TEMPO decreases mycobacterial burden in vivo through host and bacterial targets
Harrison D Black, Wenbo Xu, Elinor Hortle, Sonia I Roberston, Warwick J Britton, Amandeep Kaur, Elizabeth J New, Paul K Witting, Belal Chami, Stefan H Oehlers
bioRxiv 464586; doi: https://doi.org/10.1101/464586

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Microbiology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3701)
  • Biochemistry (7820)
  • Bioengineering (5695)
  • Bioinformatics (21343)
  • Biophysics (10603)
  • Cancer Biology (8206)
  • Cell Biology (11973)
  • Clinical Trials (138)
  • Developmental Biology (6786)
  • Ecology (10424)
  • Epidemiology (2065)
  • Evolutionary Biology (13908)
  • Genetics (9731)
  • Genomics (13108)
  • Immunology (8170)
  • Microbiology (20064)
  • Molecular Biology (7875)
  • Neuroscience (43170)
  • Paleontology (321)
  • Pathology (1282)
  • Pharmacology and Toxicology (2267)
  • Physiology (3362)
  • Plant Biology (7253)
  • Scientific Communication and Education (1316)
  • Synthetic Biology (2012)
  • Systems Biology (5550)
  • Zoology (1133)