The cyclic nitroxide antioxidant 4-methoxy-TEMPO decreases mycobacterial burden in vivo through host and bacterial targets
The cyclic nitroxide antioxidant 4-methoxy-TEMPO decreases mycobacterial burden in vivo through host and bacterial targets
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.
Black Harrison D、Roberston Sonia I、Britton Warwick J、Hortle Elinor、Oehlers Stefan H、Chami Belal、Xu Wenbo、Kaur Amandeep、Witting Paul K、New Elizabeth J
Centenary Institute, The University of Sydney||Discipline of Pathology Faculty of Medicine and Health, The University of SydneyCentenary Institute, The University of SydneyCentenary Institute, The University of Sydney||Central Clinical School Faculty of Medicine and Health, The University of SydneyCentenary Institute, The University of SydneyCentenary Institute, The University of Sydney||Central Clinical School Faculty of Medicine and Health, The University of SydneyDiscipline of Pathology Faculty of Medicine and Health, The University of SydneyCentenary Institute, The University of SydneySchool of Chemistry, The University of SydneyDiscipline of Pathology Faculty of Medicine and Health, The University of SydneySchool of Chemistry, The University of Sydney
医学研究方法基础医学微生物学
Infectionhost-directed therapyantioxidantmitochondriacell death hypoxia zebrafish
Black Harrison D,Roberston Sonia I,Britton Warwick J,Hortle Elinor,Oehlers Stefan H,Chami Belal,Xu Wenbo,Kaur Amandeep,Witting Paul K,New Elizabeth J.The cyclic nitroxide antioxidant 4-methoxy-TEMPO decreases mycobacterial burden in vivo through host and bacterial targets[EB/OL].(2025-03-28)[2025-05-04].https://www.biorxiv.org/content/10.1101/464586.点此复制
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