Temporal Manipulation of Mitochondrial Function by Virulent Francisella tularensis To Limit Inflammation and Control Cell Death

Infection and Immunity
Forrest JessopCatharine M Bosio

Abstract

Francisella tularensis subsp. tularensis is a highly pathogenic intracellular bacterium that suppresses host inflammation by impairing the metabolic shift from oxidative phosphorylation to glycolysis. Decreased mitochondrial metabolism is central to initiating a metabolic shift to glycolysis and regulating inflammation, but F. tularensis subsp. tularensis manipulation of host mitochondrial function has not been explored. We demonstrate, using extracellular flux analysis, that F. tularensis subsp. tularensis infection initially improves host macrophage mitochondrial bioenergetics in a capsule-dependent manner. Enhancement of mitochondrial function by F. tularensis subsp. tularensis allowed for modest replication and inhibition of apoptosis early after infection. However, using live cell imaging, we found that F. tularensis subsp. tularensis facilitated the loss of mitochondrial function at later time points during infection in a capsule-independent fashion. This loss of function was paired with oncosis and rapid bacterial replication. Inhibition of oncosis reduced intracellular bacterial numbers, underscoring the requirement for this process during F. tularensis subsp. tularensis infection. These findings establish that temporal...Continue Reading

References

Aug 1, 1977·The Journal of Hygiene·A M Hood
Sep 3, 1999·The Journal of Biological Chemistry·T W KelleyC B Marsh
Mar 1, 2003·The European Respiratory Journal·A Tärnvik, L Berglund
Mar 21, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Catharine M BosioJohn T Belisle
Mar 31, 2007·Annals of the New York Academy of Sciences·Anders Sjöstedt
Aug 19, 2007·Trends in Pharmacological Sciences·Keith A Webster
Mar 31, 2010·Nature Immunology·Vijay A K RathinamKatherine A Fitzgerald
Jul 6, 2011·The Biochemical Journal·Martin D Brand, David G Nicholls
Sep 10, 2011·Cellular Microbiology·Kamila Belhocine, Denise M Monack
Jun 22, 2012·Journal of Aging Research·Claus DeslerLene Juel Rasmussen
Aug 28, 2012·Science·Wen YiLinda C Hsieh-Wilson
Sep 1, 2012·Science·Richard J Youle, Alexander M van der Bliek
Oct 6, 2012·Experimental and Molecular Pathology·Priya Weerasinghe, L Maximilian Buja
Mar 13, 2014·Infection and Immunity·Christopher R DoyleDavid G Thanassi
Sep 6, 2014·Frontiers in Microbiology·Deborah D CraneCatharine M Bosio
Oct 31, 2014·The Journal of Biological Chemistry·Christopher Del NagroThomas O'Brien
Apr 1, 2015·The Journal of Cell Biology·Michelle R Bond, John A Hanover
Jun 24, 2015·Proceedings of the National Academy of Sciences of the United States of America·Michael A LobritzJames J Collins
Dec 24, 2015·The Journal of Experimental Medicine·Luke A J O'Neill, Edward J Pearce
Mar 8, 2016·Nature Reviews. Microbiology·Andrew J Olive, Christopher M Sassetti
Apr 1, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Elliott V WyattCatharine M Bosio
Dec 8, 2016·Journal of Molecular Biology·Marie MonlunBenjamin Faustin

❮ Previous
Next ❯

Citations

Aug 1, 2020·Pathogens·Paige E Allen, Juan J Martinez
Nov 12, 2019·Frontiers in Immunology·Elodie RamondAlain Charbit
Sep 5, 2020·Scientific Reports·Magdalena ProksovaJiri Stulik
Jul 25, 2019·Frontiers in Cellular and Infection Microbiology·Klara Kubelkova, Ales Macela
Feb 26, 2020·Nature Immunology·Susan K PierceNaomi Taylor

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis