Bacterial inhibition of phosphatidylcholine synthesis triggers apoptosis in the brain

The Journal of Experimental Medicine
Janine ZweignerElaine I Tuomanen

Abstract

Streptococcus pneumoniae is the most common cause of bacterial meningitis of high mortality and morbidity. Neurological sequelae include paralysis, mental retardation, and learning disorders. In humans, neurons of the hippocampus undergo apoptosis as a result of meningitis. Phosphatidylcholine (PtdCho) is an essential component of mammalian cell membranes and PtdCho deficiency, either due to chemicals or altered nutrition, leads to apoptosis, especially in hippocampal neurons. We show that apoptosis of a variety of brain cells after pneumococcal infection arises from inhibition of PtdCho biosynthesis, the first such activity described for a bacterium. Apoptosis inhibitors did not prevent the bacterial-dependent inhibition of PtdCho biosynthesis. Supplementation with exogenous lyso-phosphatidylcholine prevents cell death and treatment of mice with cytidine diphosphocholine attenuates hippocampal damage during meningitis, even after the onset of infection. We conclude that bacterial inhibition of PtdCho biosynthesis activates an apoptotic cascade that is a causative event in pathogenesis and amenable to therapeutic intervention.

References

Aug 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·J K BlusztajnU I Richardson
Feb 1, 1996·Molecular Microbiology·B SpellerbergH R Masure
Feb 12, 1998·The New England Journal of Medicine·A SchuchatB A Perkins
Oct 2, 1998·Stroke; a Journal of Cerebral Circulation·W ClarkK Hazel
Mar 23, 1999·Nature Medicine·J S BraunE I Tuomanen
Mar 27, 1999·The Journal of Biological Chemistry·I Baburina, S Jackowski
Apr 10, 1999·Journal of Neuropathology and Experimental Neurology·R NauW Brück
Apr 14, 1999·Molecular Microbiology·J R ZhangE I Tuomanen
Jul 3, 1999·The Journal of Biological Chemistry·M L AnthonyK M Brindle
Mar 29, 2000·The Journal of Biological Chemistry·R K MallampalliS Jackowski
Jul 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·G S AttardS Jackowski
Sep 7, 2000·Biochemical Pharmacology·R J WurtmanL Yu
Oct 25, 2000·The Journal of Biological Chemistry·A LykidisS Jackowski
Aug 2, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·C L YenS H Zeisel
Aug 3, 2001·The Journal of Biological Chemistry·M Q Holmes-McNaryS H Zeisel
Oct 27, 2001·The Journal of Infectious Diseases·J S BraunJ L Cleveland
Jan 10, 2002·The Journal of Clinical Investigation·Johann S BraunJoerg R Weber
Aug 13, 2002·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Olaf HoffmannJoerg R Weber
Sep 17, 2002·The Journal of Infectious Diseases·Diederik van de BeekMarinus Vermeulen
Sep 25, 2002·Journal of Neuroscience Research·Rao Muralikrishna Adibhatla, J F Hatcher
Jan 28, 2003·Progress in Lipid Research·Christian SohlenkampOtto Geiger
Jul 19, 2003·Molecular Pharmacology·Belen RamosSuzanne Jackowski
Aug 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jesus Colino, Clifford M Snapper
Aug 1, 1959·Canadian Journal of Biochemistry and Physiology·E G BLIGH, W J DYER
Jun 1, 1996·Trends in Cell Biology·A H MerrillR T Riley

❮ Previous
Next ❯

Citations

Jan 1, 2013·Molecular Neurobiology·Haviryaji S G KalluriRobert J Dempsey
Dec 28, 2010·The Journal of Infectious Diseases·Anja ReissJoerg R Weber
Apr 8, 2006·Current Opinion in Pediatrics·Denis Grandgirard, Stephen L Leib
Jun 23, 2006·Infection and Immunity·Carlos J OrihuelaElaine I Tuomanen
Jun 9, 2009·Interdisciplinary Perspectives on Infectious Diseases·U R GoonetillekeS B Gordon
Aug 18, 2012·PloS One·Khalil AlkuwaityMyron Christodoulides
Apr 16, 2013·Journal of Neuropathology and Experimental Neurology·James W Neal, Philippe Gasque
Oct 14, 2010·Journal of Neuropathology and Experimental Neurology·Caroline L BellacStephen L Leib
Jul 18, 2006·The International Journal of Biochemistry & Cell Biology·Helen M Marriott, David H Dockrell
Sep 27, 2012·Biochimica Et Biophysica Acta·Paolo Fagone, Suzanne Jackowski
Sep 3, 2014·Journal of Inherited Metabolic Disease·Saskia B WortmannRon A Wevers
Jul 27, 2006·Journal of Lipid Research·Florita C HendersonRama K Mallampalli
Sep 30, 2008·Nature Genetics·Taku MiyagawaKatsushi Tokunaga
Nov 13, 2004·The Journal of Biological Chemistry·Suzanne Jackowski, Paolo Fagone
Oct 7, 2006·Neurochemical Research·Jeng-Hsiung F PengPhilip G Rhodes
Jul 5, 2018·BMC Infectious Diseases·Jana SeeleRoland Nau

❮ Previous
Next ❯

Methods Mentioned

BETA
phosphotransferase
light microscopy
FACS
acylation

Software Mentioned

Scion Image Beta
NIH
SigmaStat

Related Concepts

Related Feeds

Bacterial Pneumonia (ASM)

Bacterial pneumonia is a prevalent and costly infection that is a significant cause of morbidity and mortality in patients of all ages. Here is the latest research.

Bacterial Pneumonia

Bacterial pneumonia is a prevalent and costly infection that is a significant cause of morbidity and mortality in patients of all ages. Here is the latest research.

Bacterial Meningitis

Bacterial meningitis continues to be an important cause of mortality and morbidity throughout the world. Here is the latest research.

Bacterial Meningitis (ASM)

Bacterial meningitis continues to be an important cause of mortality and morbidity throughout the world. Here is the latest research.

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