Monitoring global protein thiol-oxidation and protein S-mycothiolation in Mycobacterium smegmatis under hypochlorite stress.

Hillion M, Bernhardt J, Busche T, Rossius M, Maaß S, Becher D, Rawat M, Wirtz M, Hell R, Rückert C, Kalinowski J, et al. (2017)
Sci Rep 7(1): 1195.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
Es wurden keine Dateien hochgeladen. Nur Publikationsnachweis!
Hillion, M; Bernhardt, J; Busche, TobiasUniBi; Rossius, M; Maaß, S; Becher, D; Rawat, M; Wirtz, M; Hell, R; Rückert, ChristianUniBi ; Kalinowski, JörnUniBi; Antelmann, H
Abstract / Bemerkung
Mycothiol (MSH) is the major low molecular weight (LMW) thiol in Actinomycetes. Here, we used shotgun proteomics, OxICAT and RNA-seq transcriptomics to analyse protein S-mycothiolation, reversible thiol-oxidations and their impact on gene expression in Mycobacterium smegmatis under hypochlorite stress. In total, 58 S-mycothiolated proteins were identified under NaOCl stress that are involved in energy metabolism, fatty acid and mycolic acid biosynthesis, protein translation, redox regulation and detoxification. Protein S-mycothiolation was accompanied by MSH depletion in the thiol-metabolome. Quantification of the redox state of 1098 Cys residues using OxICAT revealed that 381 Cys residues (33.6%) showed >10% increased oxidations under NaOCl stress, which overlapped with 40 S-mycothiolated Cys-peptides. The absence of MSH resulted in a higher basal oxidation level of 338 Cys residues (41.1%). The RseA and RshA anti-sigma factors and the Zur and NrdR repressors were identified as NaOCl-sensitive proteins and their oxidation resulted in an up-regulation of the SigH, SigE, Zur and NrdR regulons in the RNA-seq transcriptome. In conclusion, we show here that NaOCl stress causes widespread thiol-oxidation including protein S-mycothiolation resulting in induction of antioxidant defense mechanisms in M. smegmatis. Our results further reveal that MSH is important to maintain the reduced state of protein thiols.
Sci Rep
Page URI


Hillion M, Bernhardt J, Busche T, et al. Monitoring global protein thiol-oxidation and protein S-mycothiolation in Mycobacterium smegmatis under hypochlorite stress. Sci Rep. 2017;7(1): 1195.
Hillion, M., Bernhardt, J., Busche, T., Rossius, M., Maaß, S., Becher, D., Rawat, M., et al. (2017). Monitoring global protein thiol-oxidation and protein S-mycothiolation in Mycobacterium smegmatis under hypochlorite stress. Sci Rep, 7(1), 1195. doi:10.1038/s41598-017-01179-4
Hillion, M, Bernhardt, J, Busche, Tobias, Rossius, M, Maaß, S, Becher, D, Rawat, M, et al. 2017. “Monitoring global protein thiol-oxidation and protein S-mycothiolation in Mycobacterium smegmatis under hypochlorite stress.”. Sci Rep 7 (1): 1195.
Hillion, M., Bernhardt, J., Busche, T., Rossius, M., Maaß, S., Becher, D., Rawat, M., Wirtz, M., Hell, R., Rückert, C., et al. (2017). Monitoring global protein thiol-oxidation and protein S-mycothiolation in Mycobacterium smegmatis under hypochlorite stress. Sci Rep 7:1195.
Hillion, M., et al., 2017. Monitoring global protein thiol-oxidation and protein S-mycothiolation in Mycobacterium smegmatis under hypochlorite stress. Sci Rep, 7(1): 1195.
M. Hillion, et al., “Monitoring global protein thiol-oxidation and protein S-mycothiolation in Mycobacterium smegmatis under hypochlorite stress.”, Sci Rep, vol. 7, 2017, : 1195.
Hillion, M., Bernhardt, J., Busche, T., Rossius, M., Maaß, S., Becher, D., Rawat, M., Wirtz, M., Hell, R., Rückert, C., Kalinowski, J., Antelmann, H.: Monitoring global protein thiol-oxidation and protein S-mycothiolation in Mycobacterium smegmatis under hypochlorite stress. Sci Rep. 7, : 1195 (2017).
Hillion, M, Bernhardt, J, Busche, Tobias, Rossius, M, Maaß, S, Becher, D, Rawat, M, Wirtz, M, Hell, R, Rückert, Christian, Kalinowski, Jörn, and Antelmann, H. “Monitoring global protein thiol-oxidation and protein S-mycothiolation in Mycobacterium smegmatis under hypochlorite stress.”. Sci Rep 7.1 (2017): 1195.

12 Zitationen in Europe PMC

Daten bereitgestellt von Europe PubMed Central.

Redox regulation by reversible protein S-thiolation in Gram-positive bacteria.
Imber M, Pietrzyk-Brzezinska AJ, Antelmann H., Redox Biol 20(), 2019
PMID: 30308476
Stable integration of the Mrx1-roGFP2 biosensor to monitor dynamic changes of the mycothiol redox potential in Corynebacterium glutamicum.
Tung QN, Loi VV, Busche T, Nerlich A, Mieth M, Milse J, Kalinowski J, Hocke AC, Antelmann H., Redox Biol 20(), 2019
PMID: 30481728
Quantifying changes in the bacterial thiol redox proteome during host-pathogen interaction.
Xie K, Bunse C, Marcus K, Leichert LI., Redox Biol 21(), 2019
PMID: 30682706
Mycofactocin Is Associated with Ethanol Metabolism in Mycobacteria.
Krishnamoorthy G, Kaiser P, Lozza L, Hahnke K, Mollenkopf HJ, Kaufmann SHE., MBio 10(3), 2019
PMID: 31113891
Redox-Sensing Under Hypochlorite Stress and Infection Conditions by the Rrf2-Family Repressor HypR in Staphylococcus aureus.
Loi VV, Busche T, Tedin K, Bernhardt J, Wollenhaupt J, Huyen NTT, Weise C, Kalinowski J, Wahl MC, Fulde M, Antelmann H., Antioxid Redox Signal 29(7), 2018
PMID: 29237286
Comprehensive Redox Profiling of the Thiol Proteome of Clostridium difficile.
Sievers S, Dittmann S, Jordt T, Otto A, Hochgräfe F, Riedel K., Mol Cell Proteomics 17(5), 2018
PMID: 29496906
Redox-guided small molecule antimycobacterials.
Kulkarni A, Sharma AK, Chakrapani H., IUBMB Life 70(9), 2018
PMID: 29761645
Pseudomonas aeruginosa ttcA encoding tRNA-thiolating protein requires an iron-sulfur cluster to participate in hydrogen peroxide-mediated stress protection and pathogenicity.
Romsang A, Duang-Nkern J, Khemsom K, Wongsaroj L, Saninjuk K, Fuangthong M, Vattanaviboon P, Mongkolsuk S., Sci Rep 8(1), 2018
PMID: 30089777
DksA-DnaJ redox interactions provide a signal for the activation of bacterial RNA polymerase.
Kim JS, Liu L, Fitzsimmons LF, Wang Y, Crawford MA, Mastrogiovanni M, Trujillo M, Till JKA, Radi R, Dai S, Vázquez-Torres A., Proc Natl Acad Sci U S A 115(50), 2018
PMID: 30429329
The AGXX® Antimicrobial Coating Causes a Thiol-Specific Oxidative Stress Response and Protein S-bacillithiolation in Staphylococcus aureus.
Loi VV, Busche T, Preuß T, Kalinowski J, Bernhardt J, Antelmann H., Front Microbiol 9(), 2018
PMID: 30619128
The glyceraldehyde-3-phosphate dehydrogenase GapDH of Corynebacterium diphtheriae is redox-controlled by protein S-mycothiolation under oxidative stress.
Hillion M, Imber M, Pedre B, Bernhardt J, Saleh M, Loi VV, Maaß S, Becher D, Astolfi Rosado L, Adrian L, Weise C, Hell R, Wirtz M, Messens J, Antelmann H., Sci Rep 7(1), 2017
PMID: 28694441
Transcriptome Landscape of Mycobacterium smegmatis.
Li X, Mei H, Chen F, Tang Q, Yu Z, Cao X, Andongma BT, Chou SH, He J., Front Microbiol 8(), 2017
PMID: 29326668

76 References

Daten bereitgestellt von Europe PubMed Central.

The emerging role of gasotransmitters in the pathogenesis of tuberculosis.
Chinta KC, Saini V, Glasgow JN, Mazorodze JH, Rahman MA, Reddy D, Lancaster JR Jr, Steyn AJ., Nitric Oxide 59(), 2016
PMID: 27387335
The Corynebacterium glutamicum mycothiol peroxidase is a reactive oxygen species-scavenging enzyme that shows promiscuity in thiol redox control.
Pedre B, Van Molle I, Villadangos AF, Wahni K, Vertommen D, Turell L, Erdogan H, Mateos LM, Messens J., Mol. Microbiol. 96(6), 2015
PMID: 25766783
Hypochlorite-induced oxidation of amino acids, peptides and proteins.
Hawkins CL, Pattison DI, Davies MJ., Amino Acids 25(3-4), 2003
PMID: 14661089
Function and regulation of class I ribonucleotide reductase-encoding genes in mycobacteria.
Mowa MB, Warner DF, Kaplan G, Kana BD, Mizrahi V., J. Bacteriol. 191(3), 2008
PMID: 19028890
An obligately aerobic soil bacterium activates fermentative hydrogen production to survive reductive stress during hypoxia.
Berney M, Greening C, Conrad R, Jacobs WR Jr, Cook GM., Proc. Natl. Acad. Sci. U.S.A. 111(31), 2014
PMID: 25049411
RsrA, an anti-sigma factor regulated by redox change.
Kang JG, Paget MS, Seok YJ, Hahn MY, Bae JB, Hahn JS, Kleanthous C, Buttner MJ, Roe JH., EMBO J. 18(15), 1999
PMID: 10428967
The biotin switch method for the detection of S-nitrosylated proteins.
Jaffrey SR, Snyder SH., Sci. STKE 2001(86), 2001
PMID: 11752655
The anti-sigma factor RsrA responds to oxidative stress by reburying its hydrophobic core.
Rajasekar KV, Zdanowski K, Yan J, Hopper JT, Francis ML, Seepersad C, Sharp C, Pecqueur L, Werner JM, Robinson CV, Mohammed S, Potts JR, Kleanthous C., Nat Commun 7(), 2016
PMID: 27432510
Genetic requirements for mycobacterial survival during infection.
Sassetti CM, Rubin EJ., Proc. Natl. Acad. Sci. U.S.A. 100(22), 2003
PMID: 14569030
Physiological roles of mycothiol in detoxification and tolerance to multiple poisonous chemicals in Corynebacterium glutamicum.
Liu YB, Long MX, Yin YJ, Si MR, Zhang L, Lu ZQ, Wang Y, Shen XH., Arch. Microbiol. 195(6), 2013
PMID: 23615850
Biosynthesis and functions of mycothiol, the unique protective thiol of Actinobacteria.
Newton GL, Buchmeier N, Fahey RC., Microbiol. Mol. Biol. Rev. 72(3), 2008
PMID: 18772286
S-nitroso proteome of Mycobacterium tuberculosis: Enzymes of intermediary metabolism and antioxidant defense.
Rhee KY, Erdjument-Bromage H, Tempst P, Nathan CF., Proc. Natl. Acad. Sci. U.S.A. 102(2), 2004
PMID: 15626759
Corynebacterium glutamicum methionine sulfoxide reductase A uses both mycoredoxin and thioredoxin for regeneration and oxidative stress resistance.
Si M, Zhang L, Chaudhry MT, Ding W, Xu Y, Chen C, Akbar A, Shen X, Liu SJ., Appl. Environ. Microbiol. 81(8), 2015
PMID: 25681179
Polyphosphate is a primordial chaperone.
Gray MJ, Wholey WY, Wagner NO, Cremers CM, Mueller-Schickert A, Hock NT, Krieger AG, Smith EM, Bender RA, Bardwell JC, Jakob U., Mol. Cell 53(5), 2014
PMID: 24560923
Mycothiol: a promising antitubercular target.
Nilewar SS, Kathiravan MK., Bioorg. Chem. 52(), 2013
PMID: 24368170
Mycobacterium smegmatis whmD and its homologue Mycobacterium tuberculosis whiB2 are functionally equivalent.
Raghunand TR, Bishai WR., Microbiology (Reading, Engl.) 152(Pt 9), 2006
PMID: 16946268
Adaptation of Mycobacterium smegmatis to stationary phase.
Smeulders MJ, Keer J, Speight RA, Williams HD., J. Bacteriol. 181(1), 1999
PMID: 9864340
Corynebacterium diphtheriae methionine sulfoxide reductase a exploits a unique mycothiol redox relay mechanism.
Tossounian MA, Pedre B, Wahni K, Erdogan H, Vertommen D, Van Molle I, Messens J., J. Biol. Chem. 290(18), 2015
PMID: 25752606
Mycobacterium tuberculosis tyrosine phosphatase A (PtpA) activity is modulated by S-nitrosylation.
Ecco G, Vernal J, Razzera G, Martins PA, Matiollo C, Terenzi H., Chem. Commun. (Camb.) 46(40), 2010
PMID: 20830431
Mycoredoxin-1 is one of the missing links in the oxidative stress defence mechanism of Mycobacteria.
Van Laer K, Buts L, Foloppe N, Vertommen D, Van Belle K, Wahni K, Roos G, Nilsson L, Mateos LM, Rawat M, van Nuland NA, Messens J., Mol. Microbiol. 86(4), 2012
PMID: 22970802
Global analysis of the Mycobacterium tuberculosis Zur (FurB) regulon.
Maciag A, Dainese E, Rodriguez GM, Milano A, Provvedi R, Pasca MR, Smith I, Palu G, Riccardi G, Manganelli R., J. Bacteriol. 189(3), 2006
PMID: 17098899
Mycobacterium tuberculosis WhiB1 represses transcription of the essential chaperonin GroEL2.
Stapleton MR, Smith LJ, Hunt DM, Buxton RS, Green J., Tuberculosis (Edinb) 92(4), 2012
PMID: 22464736
The redox-switch domain of Hsp33 functions as dual stress sensor.
Ilbert M, Horst J, Ahrens S, Winter J, Graf PC, Lilie H, Jakob U., Nat. Struct. Mol. Biol. 14(6), 2007
PMID: 17515905
S-bacillithiolation protects conserved and essential proteins against hypochlorite stress in firmicutes bacteria.
Chi BK, Roberts AA, Huyen TT, Basell K, Becher D, Albrecht D, Hamilton CJ, Antelmann H., Antioxid. Redox Signal. 18(11), 2012
PMID: 22938038
Redox switch of hsp33 has a novel zinc-binding motif.
Jakob U, Eser M, Bardwell JC., J. Biol. Chem. 275(49), 2000
PMID: 10976105
Pleiotropic effect of AccD5 and AccE5 depletion in acyl-coenzyme A carboxylase activity and in lipid biosynthesis in mycobacteria.
Bazet Lyonnet B, Diacovich L, Cabruja M, Bardou F, Quemard A, Gago G, Gramajo H., PLoS ONE 9(6), 2014
PMID: 24950047
Thiol-based redox switches and gene regulation.
Antelmann H, Helmann JD., Antioxid. Redox Signal. 14(6), 2010
PMID: 20626317
Activation of the redox-regulated molecular chaperone Hsp33--a two-step mechanism.
Graumann J, Lilie H, Tang X, Tucker KA, Hoffmann JH, Vijayalakshmi J, Saper M, Bardwell JC, Jakob U., Structure 9(5), 2001
PMID: 11377198
Metabolic enzymes of mycobacteria linked to antioxidant defense by a thioredoxin-like protein.
Bryk R, Lima CD, Erdjument-Bromage H, Tempst P, Nathan C., Science 295(5557), 2002
PMID: 11799204
Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia sensor.
Kumar A, Toledo JC, Patel RP, Lancaster JR Jr, Steyn AJ., Proc. Natl. Acad. Sci. U.S.A. 104(28), 2007
PMID: 17609369
Quantifying changes in the thiol redox proteome upon oxidative stress in vivo.
Leichert LI, Gehrke F, Gudiseva HV, Blackwell T, Ilbert M, Walker AK, Strahler JR, Andrews PC, Jakob U., Proc. Natl. Acad. Sci. U.S.A. 105(24), 2008
PMID: 18287020
A generic method for assignment of reliability scores applied to solvent accessibility predictions.
Petersen B, Petersen TN, Andersen P, Nielsen M, Lundegaard C., BMC Struct. Biol. 9(), 2009
PMID: 19646261
Incidence and physiological relevance of protein thiol switches.
Leichert LI, Dick TP., Biol. Chem. 396(5), 2015
PMID: 25719318
MEME SUITE: tools for motif discovery and searching.
Bailey TL, Boden M, Buske FA, Frith M, Grant CE, Clementi L, Ren J, Li WW, Noble WS., Nucleic Acids Res. 37(Web Server issue), 2009
PMID: 19458158
WebLogo: a sequence logo generator.
Crooks GE, Hon G, Chandonia JM, Brenner SE., Genome Res. 14(6), 2004
PMID: 15173120
Structure-function relationships of the Mycobacterium tuberculosis transcription factor WhiB1.
Smith LJ, Stapleton MR, Buxton RS, Green J., PLoS ONE 7(7), 2012
PMID: 22792304
S-nitrosylation of Mycobacterium tuberculosis tyrosine phosphatase A (PtpA) induces its structural instability.
Matiollo C, Ecco G, Menegatti AC, Razzera G, Vernal J, Terenzi H., Biochim. Biophys. Acta 1834(1), 2012
PMID: 23102706
Comparative analysis of mutants in the mycothiol biosynthesis pathway in Mycobacterium smegmatis.
Rawat M, Johnson C, Cadiz V, Av-Gay Y., Biochem. Biophys. Res. Commun. 363(1), 2007
PMID: 17826740
Mycothiol/mycoredoxin 1-dependent reduction of the peroxiredoxin AhpE from Mycobacterium tuberculosis.
Hugo M, Van Laer K, Reyes AM, Vertommen D, Messens J, Radi R, Trujillo M., J. Biol. Chem. 289(8), 2013
PMID: 24379404
Exact and complete short-read alignment to microbial genomes using Graphics Processing Unit programming.
Blom J, Jakobi T, Doppmeier D, Jaenicke S, Kalinowski J, Stoye J, Goesmann A., Bioinformatics 27(10), 2011
PMID: 21450712
Thiol-based redox switches in prokaryotes.
Hillion M, Antelmann H., Biol. Chem. 396(5), 2015
PMID: 25720121
Fitting a mixture model by expectation maximization to discover motifs in biopolymers.
Bailey TL, Elkan C., Proc Int Conf Intell Syst Mol Biol 2(), 1994
PMID: 7584402
Quantitative redox proteomics: the NOxICAT method.
Lindemann C, Leichert LI., Methods Mol. Biol. 893(), 2012
PMID: 22665313
Protein S-mycothiolation functions as redox-switch and thiol protection mechanism in Corynebacterium glutamicum under hypochlorite stress.
Chi BK, Busche T, Van Laer K, Basell K, Becher D, Clermont L, Seibold GM, Persicke M, Kalinowski J, Messens J, Antelmann H., Antioxid. Redox Signal. 20(4), 2013
PMID: 23886307
The inactivation mechanism of low molecular weight phosphotyrosine-protein phosphatase by H2O2.
Caselli A, Marzocchini R, Camici G, Manao G, Moneti G, Pieraccini G, Ramponi G., J. Biol. Chem. 273(49), 1998
PMID: 9829991
Distribution of thiols in microorganisms: mycothiol is a major thiol in most actinomycetes.
Newton GL, Arnold K, Price MS, Sherrill C, Delcardayre SB, Aharonowitz Y, Cohen G, Davies J, Fahey RC, Davis C., J. Bacteriol. 178(7), 1996
PMID: 8606174
Oxidative stress protection by polyphosphate--new roles for an old player.
Gray MJ, Jakob U., Curr. Opin. Microbiol. 24(), 2015
PMID: 25589044
A VapBC toxin-antitoxin module is a posttranscriptional regulator of metabolic flux in mycobacteria.
McKenzie JL, Robson J, Berney M, Smith TC, Ruthe A, Gardner PP, Arcus VL, Cook GM., J. Bacteriol. 194(9), 2012
PMID: 22366418
Ergothioneine Maintains Redox and Bioenergetic Homeostasis Essential for Drug Susceptibility and Virulence of Mycobacterium tuberculosis.
Saini V, Cumming BM, Guidry L, Lamprecht DA, Adamson JH, Reddy VP, Chinta KC, Mazorodze JH, Glasgow JN, Richard-Greenblatt M, Gomez-Velasco A, Bach H, Av-Gay Y, Eoh H, Rhee K, Steyn AJC., Cell Rep 14(3), 2016
PMID: 26774486
Comprehensive Definition of the SigH Regulon of Mycobacterium tuberculosis Reveals Transcriptional Control of Diverse Stress Responses.
Sharp JD, Singh AK, Park ST, Lyubetskaya A, Peterson MW, Gomes AL, Potluri LP, Raman S, Galagan JE, Husson RN., PLoS ONE 11(3), 2016
PMID: 27003599
Redox regulation by reversible protein S-thiolation in bacteria.
Loi VV, Rossius M, Antelmann H., Front Microbiol 6(), 2015
PMID: 25852656
Association of mycothiol with protection of Mycobacterium tuberculosis from toxic oxidants and antibiotics.
Buchmeier NA, Newton GL, Koledin T, Fahey RC., Mol. Microbiol. 47(6), 2003
PMID: 12622824
ACCase 6 is the essential acetyl-CoA carboxylase involved in fatty acid and mycolic acid biosynthesis in mycobacteria.
Kurth DG, Gago GM, de la Iglesia A, Bazet Lyonnet B, Lin TW, Morbidoni HR, Tsai SC, Gramajo H., Microbiology (Reading, Engl.) 155(Pt 8), 2009
PMID: 19423629
FIMO: scanning for occurrences of a given motif.
Grant CE, Bailey TL, Noble WS., Bioinformatics 27(7), 2011
PMID: 21330290
ReadXplorer--visualization and analysis of mapped sequences.
Hilker R, Stadermann KB, Doppmeier D, Kalinowski J, Stoye J, Straube J, Winnebald J, Goesmann A., Bioinformatics 30(16), 2014
PMID: 24790157
Mycobacterium tuberculosis WhiB1 is an essential DNA-binding protein with a nitric oxide-sensitive iron-sulfur cluster.
Smith LJ, Stapleton MR, Fullstone GJ, Crack JC, Thomson AJ, Le Brun NE, Hunt DM, Harvey E, Adinolfi S, Buxton RS, Green J., Biochem. J. 432(3), 2010
PMID: 20929442
Mechanism of metal ion activation of the diphtheria toxin repressor DtxR.
D'Aquino JA, Tetenbaum-Novatt J, White A, Berkovitch F, Ringe D., Proc. Natl. Acad. Sci. U.S.A. 102(51), 2005
PMID: 16352732
The proteasome of Mycobacterium tuberculosis is required for resistance to nitric oxide.
Darwin KH, Ehrt S, Gutierrez-Ramos JC, Weich N, Nathan CF., Science 302(5652), 2003
PMID: 14671303
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2.
Love MI, Huber W, Anders S., Genome Biol. 15(12), 2014
PMID: 25516281

Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®

PMID: 28446771
PubMed | Europe PMC

Suchen in

Google Scholar