Glutathionylation ofYersinia pestis LcrV and Its Effects on Plague Pathogenesis

MBio
Anthony MitchellOlaf Schneewind

Abstract

Glutathionylation, the formation of reversible mixed disulfides between glutathione and protein cysteine residues, is a posttranslational modification previously observed for intracellular proteins of bacteria. Here we show thatYersinia pestisLcrV, a secreted protein capping the type III secretion machine, is glutathionylated at Cys273and that this modification promotes association with host ribosomal protein S3 (RPS3), moderatesY. pestistype III effector transport and killing of macrophages, and enhances bubonic plague pathogenesis in mice and rats. Secreted LcrV was purified and analyzed by mass spectrometry to reveal glutathionylation, a modification that is abolished by the codon substitution Cys273Ala inlcrVMoreover, thelcrV C273A mutation enhanced the survival of animals in models of bubonic plague. Investigating the molecular mechanism responsible for these virulence attributes, we identified macrophage RPS3 as a ligand of LcrV, an association that is perturbed by the Cys273Ala substitution. Furthermore, macrophages infected by thelcrV C273A variant displayed accelerated apoptotic death and diminished proinflammatory cytokine release. Deletion ofgshB, which encodes glutathione synthetase ofY. pestis, resulted in undetect...Continue Reading

References

Jul 1, 1989·Transactions of the Royal Society of Tropical Medicine and Hygiene·P Slack
Nov 1, 1986·Infection and Immunity·R D PerryS C Straley
May 1, 1974·The Journal of Infectious Diseases·T H Chen, K F Meyer
Jun 1, 1969·Journal of Bacteriology·R R Brubaker
Jun 5, 1983·Journal of Molecular Biology·D Hanahan
Jul 1, 1994·The American Journal of Tropical Medicine and Hygiene·J M DollK Gage
May 1, 1997·Molecular Microbiology·L W ChengO Schneewind
Nov 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·M AchtmanE Carniel
Oct 4, 1952·Nature·M MCGEOWN, F H MALPRESS
Apr 28, 2005·The American Journal of Pathology·Florent SebbaneB Joseph Hinnebusch
Jul 26, 2005·Infection and Immunity·Katie A OverheimOlaf Schneewind
Jul 30, 2005·Science·Melanie M MarketonOlaf Schneewind
Jan 1, 1921·The Biochemical Journal·F G Hopkins
Jan 1, 1923·The Biochemical Journal·J H QuastelH E Tunnicliffe
Jun 15, 2006·Antioxidants & Redox Signaling·Lluis MasipGeorge Georgiou
Mar 19, 2008·Infection and Immunity·Lauriane E QueneeOlaf Schneewind
Jan 13, 2009·Trends in Biochemical Sciences·Isabella Dalle-DonneAldo Milzani
Oct 20, 2009·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Andrey P AnisimovVladimir L Motin
Nov 3, 2010·Nature Genetics·Giovanna MorelliMark Achtman
Dec 28, 2010·Nature Chemical Biology·Karthik VeeravalliGeorge Georgiou
Jul 9, 2011·Frontiers in Microbiology·Xiaofei Gao, Philip R Hardwidge
Dec 5, 2012·PloS One·Kirsten I BosJohannes Krause
Dec 12, 2012·Molecular Microbiology·Miryoung SongAndrés Vázquez-Torres
Dec 12, 2012·Journal of Bacteriology·Katherine Given LigtenbergOlaf Schneewind
Dec 19, 2012·Cell Host & Microbe·Christopher N LaRock, Brad T Cookson
Oct 8, 2013·PLoS Pathogens·Roger D PechousWilliam E Goldman
Jan 9, 2015·Nature·Michelle L ReniereDaniel A Portnoy
Apr 9, 2015·Frontiers in Microbiology·Vu Van LoiHaike Antelmann

❮ Previous
Next ❯

Citations

Jun 13, 2018·Journal of Bacteriology·Michelle L Reniere
Sep 20, 2019·Nature·Patrick Osei-OwusuOlaf Schneewind
Jul 2, 2020·International Journal of Molecular Sciences·Marek FolMagdalena Druszczyńska
Jun 6, 2021·Redox Biology·Joanne Wei Kay Ku, Yunn-Hwen Gan

❮ Previous
Next ❯

Methods Mentioned

BETA
fluorescence microscopy
flow cytometry
ELISA
enzyme-linked immunosorbent assay
fluorescence-activated cell sorter

Software Mentioned

Prism
ImageJ
MacSpec
BioMultiView
GraphPad Prism
Geneious
GraphPad
Bruker
ExPASy
Compute Pi /

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

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.