The MerR-family regulator NmlR is involved in the defense against oxidative stress in Streptococcus pneumoniae.

Autor: Fritsch VN; Institute of Biology-Microbiology, Freie Universität Berlin, Berlin, Germany., Linzner N; Institute of Biology-Microbiology, Freie Universität Berlin, Berlin, Germany., Busche T; Center for Biotechnology, University Bielefeld, Bielefeld, Germany.; NGS Core Facility, Medical School OWL, Bielefeld University, Bielefeld, Germany., Said N; Laboratory of Structural Biochemistry, Freie Universität Berlin, Berlin, Germany., Weise C; Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany., Kalinowski J; Center for Biotechnology, University Bielefeld, Bielefeld, Germany., Wahl MC; Laboratory of Structural Biochemistry, Freie Universität Berlin, Berlin, Germany.; Macromolecular Crystallography, Helmholtz-Zentrum Berlin für Materialien und Energie, Berlin, Germany., Antelmann H; Institute of Biology-Microbiology, Freie Universität Berlin, Berlin, Germany.
Jazyk: angličtina
Zdroj: Molecular microbiology [Mol Microbiol] 2023 Feb; Vol. 119 (2), pp. 191-207. Date of Electronic Publication: 2022 Nov 28.
DOI: 10.1111/mmi.14999
Abstrakt: Streptococcus pneumoniae has to cope with the strong oxidant hypochlorous acid (HOCl), during host-pathogen interactions. Thus, we analyzed the global gene expression profile of S. pneumoniae D39 towards HOCl stress. In the RNA-seq transcriptome, the NmlR, SifR, CtsR, HrcA, SczA and CopY regulons and the etrx1-ccdA1-msrAB2 operon were most strongly induced under HOCl stress, which participate in the oxidative, electrophile and metal stress response in S. pneumoniae. The MerR-family regulator NmlR harbors a conserved Cys52 and controls the alcohol dehydrogenase-encoding adhC gene under carbonyl and NO stress. We demonstrated that NmlR senses also HOCl stress to activate transcription of the nmlR-adhC operon. HOCl-induced transcription of adhC required Cys52 of NmlR in vivo. Using mass spectrometry, NmlR was shown to be oxidized to intersubunit disulfides or S-glutathionylated under oxidative stress in vitro. A broccoli-FLAP-based assay further showed that both NmlR disulfides significantly increased transcription initiation at the nmlR promoter by RNAP in vitro, which depends on Cys52. Phenotype analyses revealed that NmlR functions in the defense against oxidative stress and promotes survival of S. pneumoniae during macrophage infections. In conclusion, NmlR was characterized as HOCl-sensing transcriptional regulator, which activates transcription of adhC under oxidative stress by thiol switches in S. pneumoniae.
(© 2022 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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