Universität zu Köln

Chi, Bui Khanh, Busche, Tobias, Van Laer, Koen, Baesell, Katrin, Becher, Doerte, Clermont, Lina, Seibold, Gerd M., Persicke, Marcus, Kalinowski, Joern, Messens, Joris ORCID: 0000-0002-2128-8264 and Antelmann, Haike ORCID: 0000-0002-1766-4386 (2014). Protein S-Mycothiolation Functions as Redox-Switch and Thiol Protection Mechanism in Corynebacterium glutamicum Under Hypochlorite Stress. Antioxid. Redox Signal., 20 (4). S. 589 - 606. NEW ROCHELLE: MARY ANN LIEBERT, INC. ISSN 1557-7716

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Abstract

Aims: Protein S-bacillithiolation was recently discovered as important thiol protection and redox-switch mechanism in response to hypochlorite stress in Firmicutes bacteria. Here we used transcriptomics to analyze the NaOCl stress response in the mycothiol (MSH)-producing Corynebacterium glutamicum. We further applied thiol-redox proteomics and mass spectrometry (MS) to identify protein S-mycothiolation. Results: Transcriptomics revealed the strong upregulation of the disulfide stress sigma(H) regulon by NaOCl stress in C. glutamicum, including genes for the anti sigma factor (rshA), the thioredoxin and MSH pathways (trxB1, trxC, cg1375, trxB, mshC, mca, mtr) that maintain the redox balance. We identified 25 S-mycothiolated proteins in NaOCl-treated cells by liquid chromatography-tandem mass spectrometry (LC-MS/MS), including 16 proteins that are reversibly oxidized by NaOCl in the thiol-redox proteome. The S-mycothiolome includes the methionine synthase (MetE), the maltodextrin phosphorylase (MalP), the myoinositol-1-phosphate synthase (Ino1), enzymes for the biosynthesis of nucleotides (GuaB1, GuaB2, PurL, NadC), and thiamine (ThiD), translation proteins (TufA, PheT, RpsF, RplM, RpsM, RpsC), and antioxidant enzymes (Tpx, Gpx, MsrA). We further show that S-mycothiolation of the thiol peroxidase (Tpx) affects its peroxiredoxin activity in vitro that can be restored by mycoredoxin1. LC-MS/MS analysis further identified 8 proteins with S-cysteinylations in the mshC mutant suggesting that cysteine can be used for S-thiolations in the absence of MSH. Innovation and Conclusion: We identified widespread protein S-mycothiolations in the MSH-producing C. glutamicum and demonstrate that S-mycothiolation reversibly affects the peroxidase activity of Tpx. Interestingly, many targets are conserved S-thiolated across bacillithiol- and MSH-producing bacteria, which could become future drug targets in related pathogenic Gram-positives.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Chi, Bui Khanh UNSPECIFIED UNSPECIFIED UNSPECIFIED Busche, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Van Laer, Koen UNSPECIFIED UNSPECIFIED UNSPECIFIED Baesell, Katrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Becher, Doerte UNSPECIFIED UNSPECIFIED UNSPECIFIED Clermont, Lina UNSPECIFIED UNSPECIFIED UNSPECIFIED Seibold, Gerd M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Persicke, Marcus UNSPECIFIED UNSPECIFIED UNSPECIFIED Kalinowski, Joern UNSPECIFIED UNSPECIFIED UNSPECIFIED Messens, Joris UNSPECIFIED orcid.org/0000-0002-2128-8264 UNSPECIFIED Antelmann, Haike UNSPECIFIED orcid.org/0000-0002-1766-4386 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-447431
DOI:	10.1089/ars.2013.5423
Journal or Publication Title:	Antioxid. Redox Signal.
Volume:	20
Number:	4
Page Range:	S. 589 - 606
Date:	2014
Publisher:	MARY ANN LIEBERT, INC
Place of Publication:	NEW ROCHELLE
ISSN:	1557-7716
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SIGMA-FACTOR SIGH; OXIDATIVE STRESS; TRANSCRIPTIONAL REGULATOR; ESCHERICHIA-COLI; GLUTATHIONYLATION; PEROXIREDOXIN; BIOSYNTHESIS; BACILLITHIOL; MICROARRAY; EXPRESSION Multiple languages Biochemistry & Molecular Biology; Endocrinology & Metabolism Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44743