Abstract
CatR, a peroxide-sensing transcriptional repressor of Fur family, can de-repress the transcription of the catA gene encoding catalase upon peroxide stress in Streptomyces coelicolor. Since CatR-regulated genes other than catA and its own gene catR have not been identified in detail, the understanding of the role of CatR regulon is very limited. In this study, we performed transcriptomic analysis to identify genes influenced by both ΔcatR mutation and hydrogen peroxide treatment. Through ChIP-qPCR and other analyses, a new consensus sequence was found in CatR-responsive promoter region of catR gene and catA operon for direct regulation. In addition, vtlA (SCO2027) and SCO4983 were identified as new members of the CatR regulon. Expression levels of iron uptake genes were reduced by hydrogen peroxide and a DmdR1 binding sequence was identified in promoters of these genes. The increase in free iron by hydrogen peroxide was thought to suppress the iron import system by DmdR1. A putative exporter protein VtlA regulated by CatR appeared to reduce intracellular iron to prevent oxidative stress. The name vtlA (VIT1-like transporter) was proposed for iron homeostasis related gene SCO2027.
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References
Andrews, S.C. 2010. The Ferritin-like superfamily: evolution of the biological iron storeman from a rubrerythrin-like ancestor. Biochim. Biophys. Acta 1800, 691–705.
Arosio, P., Elia, L., and Poli, M. 2017. Ferritin, cellular iron storage and regulation. IUBMB Life 69, 414–422.
Bailey, T.L., Johnson, J., Grant, C.E., and Noble, W.S. 2015. The MEME suite. Nucleic Acids Res. 43, W39–W49.
Bhubhanil, S., Chamsing, J., Sittipo, P., Chaoprasid, P., Sukchawalit, R., and Mongkolsuk, S. 2014. Roles of agrobacterium tumefaciens membrane-bound ferritin (MbfA) in iron transport and resistance to iron under acidic conditions. Microbiology 160, 863–871.
Bolger, A.M., Lohse, M., and Usadel, B. 2014. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114–2120.
Cheng, Y., Yang, R., Lyu, M., Wang, S., Liu, X., Wen, Y., Song, Y., Li, J., and Chen, Z. 2018. Ider, a dtxr family iron response regulator, controls iron homeostasis, morphological differentiation, secondary metabolism, and the oxidative stress response in Streptomyces avermitilis. Appl. Environ. Microbiol. 84, e01503–18.
Cho, Y.H. and Roe, J.H. 1997. Isolation and expression of the catA gene encoding the major vegetative catalase in Streptomyces coelicolor Müller. J. Bacteriol. 179, 4049–4052.
Choi, S.H., Lee, K.L., Shin, J.H., Cho, Y.B., Cha, S.S., and Roe, J.H. 2017. Zinc-dependent regulation of zinc import and export genes by zur. Nat. Commun. 8, 15812.
Cornelis, P., Wei, Q., Andrews, S.C., and Vinckx, T. 2011. Iron homeostasis and management of oxidative stress response in bacteria. Metallomics 3, 540–549.
Dubbs, J.M. and Mongkolsuk, S. 2012. Peroxide-sensing transcriptional regulators in bacteria. J. Bacteriol. 194, 5495–5503.
Flores, F.J. and Martín, J.F. 2004. Iron-regulatory proteins Dmdr1 and Dmdr2 of Streptomyces coelicolor form two different DNA-protein complexes with iron boxes. Biochem. J. 380, 497–503.
Fuangthong, M. and Helmann, J.D. 2003. Recognition of DNA by three ferric uptake regulator (Fur) homologs in Bacillus subtilis. J. Bacteriol. 185, 6348–6357.
Gust, B., Challis, G.L., Fowler, K., Kieser, T., and Chater, K.F. 2003. PCR-targeted Streptomyces gene replacement identifies a protein domain needed for biosynthesis of the sesquiterpene soil odor geosmin. Proc. Natl. Acad. Sci. USA 100, 1541–1546.
Hahn, J.S., Oh, S.Y., Chater, K.F., Cho, Y.H., and Roe, J.H. 2000. H2O2-sensitive fur-like repressor CatR regulating the major catalase gene in Streptomyces coelicolor. J. Biol. Chem. 275, 38254–38260.
Hahn, J.S., Oh, S.Y., and Roe, J.H. 2002. Role of OxyR as a peroxide-sensing positive regulator in Streptomyces coelicolor A3(2). J. Bacteriol. 184, 5214–5222.
Herbig, A.F. and Helmann, J.D. 2001. Roles of metal ions and hydrogen peroxide in modulating the interaction of the Bacillus subtilis PerR peroxide regulon repressor with operator DNA. Mol. Microbiol. 41, 849–859.
Huerta-Cepas, J., Szklarczyk, D., Heller, D., Hernández-Plaza, A., Forslund, S.K., Cook, H., Mende, D.R., Letunic, I., Rattei, T., Jensen, L.J., et al. 2019. eggNOG 5.0: A hierarchical, functionally and phylogenetically annotated orthology resource based on 5090 organisms and 2502 viruses. Nucleic Acids Res. 47, D309–D314.
Imlay, J.A. 2003. Pathways of oxidative damage. Annu. Rev. Microbiol. 57, 395–418.
Imlay, J.A. 2013. The molecular mechanisms and physiological consequences of oxidative stress: lessons from a model bacterium. Nat. Rev. Microbiol. 11, 443–454.
Jeong, Y., Kim, J.N., Kim, M.W., Bucca, G., Cho, S., Yoon, Y.J., Kim, B.G., Roe, J.H., Kim, S.C., Smith, C.P., et al. 2016. The dynamic transcriptional and translational landscape of the model antibiotic producer Streptomyces coelicolor A3(2). Nat. Commun. 7, 11605.
Kieser, T., Bibb, M.J., Buttner, M.J., Chater, K.F., and Hopwood, D.A. 2000. Practical Streptomyces Genetics. John Innes Centre, Norwich, England.
Krogh, A., Larsson, B., von Heijne, G., and Sonnhammer, E.L. 2001. Predicting transmembrane protein topology with a hidden markov model: application to complete genomes. J. Mol. Biol. 305, 567–580.
Kumar, S., Stecher, G., and Tamura, K. 2016. MEGA7: Molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol. Biol. Evol. 33, 1870–1874.
Labbé, S., Khan, M.G.M., and Jacques, J.F. 2013. Iron uptake and regulation in Schizosaccharomyces pombe. Curr. Opin. Microbiol. 16, 669–676.
Langmead, B. and Salzberg, S.L. 2012. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359.
Lee, J.W. and Helmann, J.D. 2006. The PerR transcription factor senses H2O2 by metal-catalysed histidine oxidation. Nature 440, 363–367.
Lee, C., Lee, S.M., Mukhopadhyay, P., Kim, S.J., Lee, S.C., Ahn, W.S., Yu, M.H., Storz, G., and Ryu, S.E. 2004a. Redox regulation of OxyR requires specific disulfide bond formation involving a rapid kinetic reaction path. Nat. Struct. Mol. Biol. 11, 1179–1185.
Lee, J.H., Yeo, W.S., and Roe, J.H. 2004b. Induction of the sufA operon encoding Fe-S assembly proteins by superoxide generators and hydrogen peroxide: Involvement of OxyR, IHF and an unidentified oxidant-responsive factor. Mol. Microbiol. 51, 1745–1755.
Lee, K.C., Yeo, W.S., and Roe, J.H. 2008. Oxidant-responsive induction of the suf operon, encoding a Fe-S assembly system, through Fur and IscR in Escherichia coli. J. Bacteriol. 190, 8244–8247.
Lee, K.L., Yoo, J.S., Oh, G.S., Singh, A.K., and Roe, J.H. 2017. Simultaneous activation of iron- and thiol-based sensor-regulator systems by redox-active compounds. Front. Microbiol. 8, 139.
Li, L., Chen, O.S., McVey Ward, D., and Kaplan, J. 2001. CCC1 is a transporter that mediates vacuolar iron storage in yeast. J. Biol. Chem. 276, 29515–29519.
Liao, Y., Smyth, G.K., and Shi, W. 2013. The subread aligner: fast, accurate and scalable read map** by seed-and-vote. Nucleic Acids Res. 41, e108.
Liu, Y., Bauer, S.C., and Imlay, J.A. 2011. The YaaA protein of the Escherichia coli OxyR regulon lessens hydrogen peroxide toxicity by diminishing the amount of intracellular unincorporated iron. J. Bacteriol. 193, 2186–2196.
Liu, X., Sun, M., Cheng, Y., Yang, R., Wen, Y., Chen, Z., and Li, J. 2016. OxyR is a key regulator in response to oxidative stress in Streptomyces avermitilis. Microbiology 162, 707–716.
Love, M.I., Huber, W., and Anders, S. 2014. Moderated estimation of fold change and dispersion for RNA-seq data with DEseq2. Genome Biol. 15, 550.
Mishra, S. and Imlay, J. 2012. Why do bacteria use so many enzymes to scavenge hydrogen peroxide? Arch. Biochem. Biophys. 525, 145–160.
Myronovskyi, M., Welle, E., Fedorenko, V., and Luzhetskyy, A. 2011. β-Glucuronidase as a sensitive and versatile reporter in actinomycetes. Appl. Environ. Microbiol. 77, 5370–5383.
Pi, H. and Helmann, J.D. 2017. Ferrous iron efflux systems in bacteria. Metallomics 9, 840–851.
Pouliot, B., Jbel, M., Mercier, A., and Labbé, S. 2010. abc3 + encodes an iron-regulated vacuolar ABC-type transporter in Schizosaccharomyces pombe. Eukaryot. Cell 9, 59–73.
Ruangkiattikul, N., Bhubhanil, S., Chamsing, J., Niamyim, P., Sukchawalit, R., and Mongkolsuk, S. 2012. Agrobacterium tumefaciens membrane-bound ferritin plays a role in protection against hydrogen peroxide toxicity and is negatively regulated by the iron response regulator. FEMS Microbiol. Lett. 329, 87–92.
Sorribes-Dauden, R., Peris, D., Martínez-Pastor, M.T., and Puig, S. 2020. Structure and function of the vacuolar Ccc1/VIT1 family of iron transporters and its regulation in fungi. Comput. Struct. Biotechnol. J. 18, 3712–3722.
VanderWal, A.R., Makthal, N., Pinochet-Barros, A., Helmann, J.D., Olsen, R.J., and Kumaraswami, M. 2017. Iron efflux by PmtA is critical for oxidative stress resistance and contributes significantly to Group A Streptococcus virulence. Infect. Immun. 85, e00091–17.
Zheng, M., Aslund, F., and Storz, G. 1998. Activation of the OxyR transcription factor by reversible disulfide bond formation. Science 279, 1718–1721.
Zheng, M., Doan, B., Schneider, T.D., and Storz, G. 1999. OxyR and SoxRS regulation of fur. J. Bacteriol. 181, 4639–4643.
Zheng, M., Wang, X., Templeton, L.J., Smulski, D.R., LaRossa, R.A., and Storz, G. 2001. DNA microarray-mediated transcriptional profiling of the Escherichia coli response to hydrogen peroxide. J. Bacteriol. 183, 4562–4570.
Acknowledgements
This research was supported by a grant (2018R1D1A1B0704-6585 to K.-L.L and 2020R1I1A1A01052942 to Y.-J.C) of the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Republic of Korea. This work was also supported by a grant (2017R1A2A1A05000735 to J.-H.R.) of the NRF funded by the Ministry of Education, Science, and Technology (MEST), Republic of Korea. Y.K. was supported by B.K. Plus Fellowship for Biological Sciences at Seoul National University.
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YK and KL design the experiments. YK performed the experiments. YK, YC, KL, and JR analyzed and interpreted the data. YK, YC, JP, KL, and JR prepared the manuscript. YK, YC and KL wrote the manuscript. All authors reviewed the manuscript.
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Kim, Y., Roe, JH., Park, JH. et al. Regulation of iron homeostasis by peroxide-sensitive CatR, a Fur-family regulator in Streptomyces coelicolor. J Microbiol. 59, 1083–1091 (2021). https://doi.org/10.1007/s12275-021-1457-1
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DOI: https://doi.org/10.1007/s12275-021-1457-1