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dc.contributor.authorBlack, Harrison
dc.contributor.authorXu, Wenbo
dc.contributor.authorHortle, Elinor
dc.contributor.authorRobertson, Sonia
dc.contributor.authorBritton, Warwick
dc.contributor.authorKaur, Amandeep
dc.contributor.authorNew, Elizabeth
dc.contributor.authorWitting, Paul
dc.contributor.authorChami, Belal
dc.contributor.authorOehlers, Stefan
dc.date.accessioned2020-02-12
dc.date.available2020-02-12
dc.date.issued2019-05-01
dc.identifier.citationBlack, H. D., Xu, W., Hortle, E., Robertson, S. I., Britton, W. J., Kaur, A., … Oehlers, S. H. (2019). The cyclic nitroxide antioxidant 4-methoxy-TEMPO decreases mycobacterial burden in vivo through host and bacterial targets. Free Radical Biology and Medicine, 135, 157–166. https://doi.org/10.1016/j.freeradbiomed.2019.03.010en_AU
dc.identifier.urihttps://hdl.handle.net/2123/21834
dc.description.abstractTuberculosis 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.en_AU
dc.description.sponsorshipThis work was supported by the Australian National Health and Medical Research Council grants APP1099912 and APP1053407; The University of Sydney, Australia Fellowship G197581; NSW Ministry of Health, Australia under the NSW Health Early-Mid Career Fellowships Scheme H18/31086; and the Kenyon Family Inflammation Award (S.H.O.).en_AU
dc.language.isoenen_AU
dc.publisherElsevieren_AU
dc.relationNHMRC APP1053407 and APP1099912en_AU
dc.subjectAntioxidanten_AU
dc.subjectCell deathen_AU
dc.subjectHost-directed therapyen_AU
dc.subjectHypoxiaen_AU
dc.subjectInfectionen_AU
dc.subjectMitochondriaen_AU
dc.subjectZebrafishen_AU
dc.titleThe cyclic nitroxide antioxidant 4-methoxy-TEMPO decreases mycobacterial burden in vivo through host and bacterial targetsen_AU
dc.typeArticleen_AU
dc.subject.asrcFoR::110707 - Innate Immunityen_AU
dc.subject.asrcFoR::110801 - Medical Bacteriologyen_AU
dc.identifier.doi10.1016/j.freeradbiomed.2019.03.010
dc.type.pubtypePost-printen_AU


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