Transcriptional response of Corynebacterium glutamicum ATCC 13032 to hydrogen peroxide stress and characterization of the OxyR regulon

Milse J, Petri K, Rückert C, Kalinowski J (2014)
Journal of Biotechnology 190: 40-54.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
Es wurden keine Dateien hochgeladen. Nur Publikationsnachweis!
Abstract / Bemerkung
: The aerobic soil bacterium Corynebacterium glutamicum ATCC 13032 has a remarkable natural resistance to hydrogen peroxide. A major player in hydrogen peroxide defense is the LysR type transcriptional regulator OxyR, homologs of which are present in a wide range of bacteria. In this study, the global transcriptional response of C. glutamicum to oxidative stress induced by hydrogen peroxide was examined using whole genome DNA microarrays, demonstrating the dynamic reaction of the regulatory networks. Deletion of oxyR resulted in an increased resistance of the C. glutamicum mutant to hydrogen peroxide. By performing DNA microarray hybridizations and RT-qPCR, differentially expressed genes were detected in the mutant. The direct control by OxyR was verified by electrophoretic mobility shift assays for twelve target regions. The results demonstrated that OxyR in C. glutamicum acts as a transcriptional repressor under non-stress conditions for a total of 23 genes. The regulated genes encode proteins related to oxidative stress response (e.g. katA), iron homeostasis (e.g. dps) and sulfur metabolism (e.g. suf cluster). Besides the regulator of the suf cluster, SufR, OxyR regulated the gene cg1695 encoding a putative transcriptional regulator, indicating the role of OxyR as a master regulator in defense against oxidative stress. Using a modified DNase footprint approach, the OxyR-binding sites in five target promoter regions, katA, cydA, hemH, dps and cg1292, were localized and in each upstream region at least two overlapping binding sites were found. The DNA regions protected by the OxyR protein are about 56 bp in length and do not have evident sequence similarities. Still, by giving an insight in the H2O2 stimulon and extending the OxyR regulon this study considerably contributes to the understanding of the response of C. glutamicum to hydrogen peroxide-mediated oxidative stress.
Journal of Biotechnology
Page URI


Milse J, Petri K, Rückert C, Kalinowski J. Transcriptional response of Corynebacterium glutamicum ATCC 13032 to hydrogen peroxide stress and characterization of the OxyR regulon. Journal of Biotechnology. 2014;190:40-54.
Milse, J., Petri, K., Rückert, C., & Kalinowski, J. (2014). Transcriptional response of Corynebacterium glutamicum ATCC 13032 to hydrogen peroxide stress and characterization of the OxyR regulon. Journal of Biotechnology, 190, 40-54. doi:10.1016/j.jbiotec.2014.07.452
Milse, Johanna, Petri, Kathrin, Rückert, Christian, and Kalinowski, Jörn. 2014. “Transcriptional response of Corynebacterium glutamicum ATCC 13032 to hydrogen peroxide stress and characterization of the OxyR regulon”. Journal of Biotechnology 190: 40-54.
Milse, J., Petri, K., Rückert, C., and Kalinowski, J. (2014). Transcriptional response of Corynebacterium glutamicum ATCC 13032 to hydrogen peroxide stress and characterization of the OxyR regulon. Journal of Biotechnology 190, 40-54.
Milse, J., et al., 2014. Transcriptional response of Corynebacterium glutamicum ATCC 13032 to hydrogen peroxide stress and characterization of the OxyR regulon. Journal of Biotechnology, 190, p 40-54.
J. Milse, et al., “Transcriptional response of Corynebacterium glutamicum ATCC 13032 to hydrogen peroxide stress and characterization of the OxyR regulon”, Journal of Biotechnology, vol. 190, 2014, pp. 40-54.
Milse, J., Petri, K., Rückert, C., Kalinowski, J.: Transcriptional response of Corynebacterium glutamicum ATCC 13032 to hydrogen peroxide stress and characterization of the OxyR regulon. Journal of Biotechnology. 190, 40-54 (2014).
Milse, Johanna, Petri, Kathrin, Rückert, Christian, and Kalinowski, Jörn. “Transcriptional response of Corynebacterium glutamicum ATCC 13032 to hydrogen peroxide stress and characterization of the OxyR regulon”. Journal of Biotechnology 190 (2014): 40-54.

18 Zitationen in Europe PMC

Daten bereitgestellt von Europe PubMed Central.

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
Acinetobacter baumannii OxyR Regulates the Transcriptional Response to Hydrogen Peroxide.
Juttukonda LJ, Green ER, Lonergan ZR, Heffern MC, Chang CJ, Skaar EP., Infect Immun 87(1), 2019
PMID: 30297527
Deciphering the Adaptation of Corynebacterium glutamicum in Transition from Aerobiosis via Microaerobiosis to Anaerobiosis.
Lange J, Münch E, Müller J, Busche T, Kalinowski J, Takors R, Blombach B., Genes (Basel) 9(6), 2018
PMID: 29899275
Structural snapshots of OxyR reveal the peroxidatic mechanism of H2O2 sensing.
Pedre B, Young D, Charlier D, Mourenza Á, Rosado LA, Marcos-Pascual L, Wahni K, Martens E, G de la Rubia A, Belousov VV, Mateos LM, Messens J., Proc Natl Acad Sci U S A 115(50), 2018
PMID: 30463959
OhsR acts as an organic peroxide-sensing transcriptional activator using an S-mycothiolation mechanism in Corynebacterium glutamicum.
Si M, Su T, Chen C, Liu J, Gong Z, Che C, Li G, Yang G., Microb Cell Fact 17(1), 2018
PMID: 30587200
Graded Response of the Multifunctional 2-Cysteine Peroxiredoxin, CgPrx, to Increasing Levels of Hydrogen Peroxide in Corynebacterium glutamicum.
Si M, Wang T, Pan J, Lin J, Chen C, Wei Y, Lu Z, Wei G, Shen X., Antioxid Redox Signal 26(1), 2017
PMID: 27324811
Metabolic profile of 1,5-diaminopentane producing Corynebacterium glutamicum under scale-down conditions: Blueprint for robustness to bioreactor inhomogeneities.
Limberg MH, Schulte J, Aryani T, Mahr R, Baumgart M, Bott M, Wiechert W, Oldiges M., Biotechnol Bioeng 114(3), 2017
PMID: 27641904
The pupylation machinery is involved in iron homeostasis by targeting the iron storage protein ferritin.
Küberl A, Polen T, Bott M., Proc Natl Acad Sci U S A 113(17), 2016
PMID: 27078093
The novel regulatory ncRNA, NfiS, optimizes nitrogen fixation via base pairing with the nitrogenase gene nifK mRNA in Pseudomonas stutzeri A1501.
Zhan Y, Yan Y, Deng Z, Chen M, Lu W, Lu C, Shang L, Yang Z, Zhang W, Wang W, Li Y, Ke Q, Lu J, Xu Y, Zhang L, Xie Z, Cheng Q, Elmerich C, Lin M., Proc Natl Acad Sci U S A 113(30), 2016
PMID: 27407147
In silico identification of essential proteins in Corynebacterium pseudotuberculosis based on protein-protein interaction networks.
Folador EL, de Carvalho PV, Silva WM, Ferreira RS, Silva A, Gromiha M, Ghosh P, Barh D, Azevedo V, Röttger R., BMC Syst Biol 10(1), 2016
PMID: 27814699
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
Thiol-based redox switches in prokaryotes.
Hillion M, Antelmann H., Biol Chem 396(5), 2015
PMID: 25720121

73 References

Daten bereitgestellt von Europe PubMed Central.

Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ., Nucleic Acids Res. 25(17), 1997
PMID: 9254694
A small, stable RNA induced by oxidative stress: role as a pleiotropic regulator and antimutator.
Altuvia S, Weinstein-Fischer D, Zhang A, Postow L, Storz G., Cell 90(1), 1997
PMID: 9230301
Oxidative stress in submerged cultures of fungi.
Bai Z, Harvey LM, McNeil B., Crit. Rev. Biotechnol. 23(4), 2003
PMID: 15224892
The value of position-specific priors in motif discovery using MEME.
Bailey TL, Boden M, Whitington T, Machanick P., BMC Bioinformatics 11(), 2010
PMID: 20380693
Exact and complete short-read alignment to microbial genomes using Graphics Processing Unit programming
Blom, Bioinforma (Oxf. Engl.) 27(), 2011
The cytochrome bd respiratory oxygen reductases.
Borisov VB, Gennis RB, Hemp J, Verkhovsky MI., Biochim. Biophys. Acta 1807(11), 2011
PMID: 21756872
Proteasomal protein degradation in Mycobacteria is dependent upon a prokaryotic ubiquitin-like protein.
Burns KE, Liu WT, Boshoff HI, Dorrestein PC, Barry CE 3rd., J. Biol. Chem. 284(5), 2008
PMID: 19028679
The complete genome sequence and analysis of Corynebacterium diphtheriae NCTC13129.
Cerdeno-Tarraga AM, Efstratiou A, Dover LG, Holden MT, Pallen M, Bentley SD, Besra GS, Churcher C, James KD, De Zoysa A, Chillingworth T, Cronin A, Dowd L, Feltwell T, Hamlin N, Holroyd S, Jagels K, Moule S, Quail MA, Rabbinowitsch E, Rutherford KM, Thomson NR, Unwin L, Whitehead S, Barrell BG, Parkhill J., Nucleic Acids Res. 31(22), 2003
PMID: 14602910
Structural basis of the redox switch in the OxyR transcription factor.
Choi H, Kim S, Mukhopadhyay P, Cho S, Woo J, Storz G, Ryu SE., Cell 105(1), 2001
PMID: 11301006
EMMA 2--a MAGE-compliant system for the collaborative analysis and integration of microarray data.
Dondrup M, Albaum SP, Griebel T, Henckel K, Junemann S, Kahlke T, Kleindt CK, Kuster H, Linke B, Mertens D, Mittard-Runte V, Neuweger H, Runte KJ, Tauch A, Tille F, Puhler A, Goesmann A., BMC Bioinformatics 10(), 2009
PMID: 19200358
Functional genomics of pH homeostasis in Corynebacterium glutamicum revealed novel links between pH response, oxidative stress, iron homeostasis and methionine synthesis.
Follmann M, Ochrombel I, Kramer R, Trotschel C, Poetsch A, Ruckert C, Huser A, Persicke M, Seiferling D, Kalinowski J, Marin K., BMC Genomics 10(), 2009
PMID: 20025733
Predominant role of catalase in the disposal of hydrogen peroxide within human erythrocytes.
Gaetani GF, Ferraris AM, Rolfo M, Mangerini R, Arena S, Kirkman HN., Blood 87(4), 1996
PMID: 8608252

Green, 2012
Role of proline under changing environment: a review
Hayat, Plant Signal. Behav. (), 2012
OxyR: a molecular code for redox sensing?
Helmann, Sci. STKE Signal Transduct. Knowl. Environ. (), 2002
Industrial production of amino acids by coryneform bacteria.
Hermann T., J. Biotechnol. 104(1-3), 2003
PMID: 12948636
Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extension.
Horton RM, Hunt HD, Ho SN, Pullen JK, Pease LR., Gene 77(1), 1989
PMID: 2744488
Development of a Corynebacterium glutamicum DNA microarray and validation by genome-wide expression profiling during growth with propionate as carbon source.
Huser AT, Becker A, Brune I, Dondrup M, Kalinowski J, Plassmeier J, Puhler A, Wiegrabe I, Tauch A., J. Biotechnol. 106(2-3), 2003
PMID: 14651867
OxyR tightly regulates catalase expression in Neisseria meningitidis through both repression and activation mechanisms.
Ieva R, Roncarati D, Metruccio MM, Seib KL, Scarlato V, Delany I., Mol. Microbiol. 70(5), 2008
PMID: 18990187
Cellular defenses against superoxide and hydrogen peroxide.
Imlay JA., Annu. Rev. Biochem. 77(), 2008
PMID: 18173371
Role of cytochrome bd oxidase from Corynebacterium glutamicum in growth and lysine production.
Kabus A, Niebisch A, Bott M., Appl. Environ. Microbiol. 73(3), 2006
PMID: 17142369
The complete Corynebacterium glutamicum ATCC 13032 genome sequence and its impact on the production of L-aspartate-derived amino acids and vitamins.
Kalinowski J, Bathe B, Bartels D, Bischoff N, Bott M, Burkovski A, Dusch N, Eggeling L, Eikmanns BJ, Gaigalat L, Goesmann A, Hartmann M, Huthmacher K, Kramer R, Linke B, McHardy AC, Meyer F, Mockel B, Pfefferle W, Puhler A, Rey DA, Ruckert C, Rupp O, Sahm H, Wendisch VF, Wiegrabe I, Tauch A., J. Biotechnol. 104(1-3), 2003
PMID: 12948626
Conversion of Corynebacterium glutamicum from an aerobic respiring to an aerobic fermenting bacterium by inactivation of the respiratory chain
Koch-Koerfges, Biochim. Biophys. Acta (), 2013
Physiological response of Corynebacterium glutamicum to oxidative stress induced by deletion of the transcriptional repressor McbR
Krömer, Microbiol. Read. Engl. 154(), 2008
Pupylated proteins in Corynebacterium glutamicum revealed by MudPIT analysis.
Kuberl A, Franzel B, Eggeling L, Polen T, Wolters DA, Bott M., Proteomics 14(12), 2014
PMID: 24737727
Clustal W and Clustal X version 2.0
Larkin, Bioinforma (Oxf. Engl.) 23(), 2007
Redox regulation of OxyR requires specific disulfide bond formation involving a rapid kinetic reaction path.
Lee C, Lee SM, Mukhopadhyay P, Kim SJ, Lee SC, Ahn WS, Yu MH, Storz G, Ryu SE., Nat. Struct. Mol. Biol. 11(12), 2004
PMID: 15543158
Roles of respiratory oxidases in protecting Escherichia coli K12 from oxidative stress.
Lindqvist A, Membrillo-Hernandez J, Poole RK, Cook GM., Antonie Van Leeuwenhoek 78(1), 2000
PMID: 11016692
Structure and function of the LysR-type transcriptional regulator (LTTR) family proteins
Maddocks, Microbiol. Read. Engl. 154(), 2008
Why do bacteria use so many enzymes to scavenge hydrogen peroxide?
Mishra S, Imlay J., Arch. Biochem. Biophys. 525(2), 2012
PMID: 22609271
Isolation and characterization of visible light-sensitive mutants of Escherichia coli K12.
Miyamoto K, Nakahigashi K, Nishimura K, Inokuchi H., J. Mol. Biol. 219(3), 1991
PMID: 2051480
DIALIGN: finding local similarities by multiple sequence alignment
Morgenstern, Bioinforma (Oxf. Engl.) 14(), 1998
Ferritin and the response to oxidative stress.
Orino K, Lehman L, Tsuji Y, Ayaki H, Torti SV, Torti FM., Biochem. J. 357(Pt 1), 2001
PMID: 11415455
Comprehensive analysis of the Corynebacterium glutamicum transcriptome using an improved RNAseq technique.
Pfeifer-Sancar K, Mentz A, Ruckert C, Kalinowski J., BMC Genomics 14(), 2013
PMID: 24341750
Molecular mechanism of the regulation of Bacillus subtilis gltAB expression by GltC.
Picossi S, Belitsky BR, Sonenshein AL., J. Mol. Biol. 365(5), 2006
PMID: 17134717
Redundancy of aerobic respiratory chains in bacteria? Routes, reasons and regulation.
Poole RK, Cook GM., Adv. Microb. Physiol. 43(), 2000
PMID: 10907557
Iron/sulfur proteins biogenesis in prokaryotes: formation, regulation and diversity.
Roche B, Aussel L, Ezraty B, Mandin P, Py B, Barras F., Biochim. Biophys. Acta 1827(3), 2013
PMID: 23298813
Functional genomics and expression analysis of the Corynebacterium glutamicum fpr2-cysIXHDNYZ gene cluster involved in assimilatory sulphate reduction.
Ruckert C, Koch DJ, Rey DA, Albersmeier A, Mormann S, Puhler A, Kalinowski J., BMC Genomics 6(), 2005
PMID: 16159395
Molecular biology of the LysR family of transcriptional regulators.
Schell MA., Annu. Rev. Microbiol. 47(), 1993
PMID: 8257110
Complete genome sequence, lifestyle, and multi-drug resistance of the human pathogen Corynebacterium resistens DSM 45100 isolated from blood samples of a leukemia patient.
Schroder J, Maus I, Meyer K, Wordemann S, Blom J, Jaenicke S, Schneider J, Trost E, Tauch A., BMC Genomics 13(), 2012
PMID: 22524407
Characterization of the OxyR regulon of Neisseria gonorrhoeae.
Seib KL, Wu HJ, Srikhanta YN, Edwards JL, Falsetta ML, Hamilton AJ, Maguire TL, Grimmond SM, Apicella MA, McEwan AG, Jennings MP., Mol. Microbiol. 63(1), 2006
PMID: 17140413
Mycobacteria and the intraphagosomal environment: take it with a pinch of salt(s)!
Soldati, Traffic Cph. Den. 13(), 2012
Microbiological and clinical features of Corynebacterium urealyticum: urinary tract stones and genomics as the Rosetta Stone
Soriano, Clin. Microbiol. Infect.: Off. Publ. Eur. Soc. Clin. Microbiol. Infect. Dis. 14(), 2008
Yeast flavin-containing monooxygenase generates oxidizing equivalents that control protein folding in the endoplasmic reticulum.
Suh JK, Poulsen LL, Ziegler DM, Robertus JD., Proc. Natl. Acad. Sci. U.S.A. 96(6), 1999
PMID: 10077572
Multidegenerate DNA recognition by the OxyR transcriptional regulator.
Tartaglia LA, Gimeno CJ, Storz G, Ames BN., J. Biol. Chem. 267(3), 1992
PMID: 1730735
Efficient electrotransformation of corynebacterium diphtheriae with a mini-replicon derived from the Corynebacterium glutamicum plasmid pGA1.
Tauch A, Kirchner O, Loffler B, Gotker S, Puhler A, Kalinowski J., Curr. Microbiol. 45(5), 2002
PMID: 12232668
OxyR acts as a transcriptional repressor of hydrogen peroxide-inducible antioxidant genes in Corynebacterium glutamicum R
Teramoto, FEBS J. (), 2013
Redox-dependent shift of OxyR-DNA contacts along an extended DNA-binding site: a mechanism for differential promoter selection.
Toledano MB, Kullik I, Trinh F, Baird PT, Schneider TD, Storz G., Cell 78(5), 1994
PMID: 8087856
[Terminal oxidases in different genera of the family Microbacteriaceae]
Trutko SM, Evtushenko LI, Dorofeeva LV, Shliapnikov MG, Gavrish EIu, Suzina NE, Akimenko VK., Mikrobiologiia 72(3), 2003
PMID: 12901002
OxyR acts as a repressor of catalase expression in Neisseria gonorrhoeae.
Tseng HJ, McEwan AG, Apicella MA, Jennings MP., Infect. Immun. 71(1), 2003
PMID: 12496210
The DtxR regulon of Corynebacterium glutamicum.
Wennerhold J, Bott M., J. Bacteriol. 188(8), 2006
PMID: 16585752
Activation of the OxyR transcription factor by reversible disulfide bond formation.
Zheng M, Aslund F, Storz G., Science 279(5357), 1998
PMID: 9497290

Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®

PMID: 25107507
PubMed | Europe PMC

Suchen in

Google Scholar