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Structural and Functional Analyses of the Flavoprotein Disulfide Reductase FN0820 of Fusobacterium nucleatum

  • Microbial Physiology and Biochemistry
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Abstract

Escherichia coli RclA and Staphylococcus aureus MerA are part of the Group I flavoprotein disulfide reductase (FDR) family and have been implicated in the contribution to bacterial pathogenesis by defending against the host immune response. Fusobacterium nucleatum is a pathogenic, anaerobic Gram-negative bacterial species commonly found in the human oral cavity and gastrointestinal tract. In this study, we discovered that the F. nucleatum protein FN0820, belonging to the Group I FDR family, exhibited a higher activity of a Cu2+-dependent NADH oxidase than E. coli RclA. Moreover, FN0820 decreased the dissolved oxygen level in the solution with higher NADH oxidase activity. We found that L-tryptophan and its analog 5-hydroxytryptophan inhibit the FN0820 activities of NADH oxidase and the concomitant reduction of oxygen. Our results have implications for developing new treatment strategies against pathogens that defend the host immune response with Group I FDRs.

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The data underlying the results are available as part of the article and further data are available from the corresponding author on reasonable request.

References

  • Baek, Y., Kim, J., Ahn, J., Jo, I., Hong, S., Ryu, S., & Ha, N. C. (2020). Structure and function of the hypochlorous acid–induced flavoprotein RclA from Escherichia coli. Journal of Biological Chemistry, 295, 3202–3212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Basic, A., Blomqvist, M., Dahlén, G., & Svensäter, G. (2017). The proteins of Fusobacterium spp. involved in hydrogen sulfide production from L-cysteine. BMC Microbiology, 17, 61.

    Article  PubMed  PubMed Central  Google Scholar 

  • Brennan, C. A., & Garrett, W. S. (2019). Fusobacterium nucleatum—symbiont, opportunist and oncobacterium. Nature Reviews Microbiology, 17, 156–166.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Derke, R. M., Barron, A. J., Billiot, C. E., Chaple, I. F., Lapi, S. E., Broderick, N. A., & Gray, M. J. (2020). The Cu (II) reductase RclA protects Escherichia coli against the combination of hypochlorous acid and intracellular copper. mBio, 11, e01905–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Diaz, P. I., Zilm, P. S., & Rogers, A. H. (2000). The response to oxidative stress of Fusobacterium nucleatum grown in continuous culture. FEMS Microbiology Letters, 187, 31–34.

    Article  CAS  PubMed  Google Scholar 

  • Diaz, P. I., Zilm, P. S., & Rogers, A. H. (2002). Fusobacterium nucleatum supports the growth of Porphyromonas gingivalis in oxygenated and carbon-dioxide-depleted environments. Microbiology, 148, 467–472.

    Article  CAS  PubMed  Google Scholar 

  • Guo, L., Shokeen, B., He, X., Shi, W., & Lux, R. (2017). Streptococcus mutans SpaP binds to RadD of Fusobacterium nucleatum ssp. polymorphum. Molecular Oral Microbiology, 32, 355–364.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gursoy, U. K., Pöllänen, M., Könönen, E., & Uitto, V. J. (2010). Biofilm formation enhances the oxygen tolerance and invasiveness of Fusobacterium nucleatum in an oral mucosa culture model. Journal of Periodontology, 81, 1084–1091.

    Article  CAS  PubMed  Google Scholar 

  • Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021). Highly accurate protein structure prediction with AlphaFold. Nature, 596, 583–589.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kleiger, G., & Eisenberg, D. (2002). GXXXG and GXXXA motifs stabilize FAD and NAD(P)-binding Rossmann folds through Cα–H···O hydrogen bonds and van der Waals interactions. Journal of Molecular Biology, 323, 69–76.

    Article  CAS  PubMed  Google Scholar 

  • Ledwidge, R., Patel, B., Dong, A., Fiedler, D., Falkowski, M., Zelikova, J., Summers, A. O., Pai, E. F., & Miller, S. M. (2005). NmerA, the metal binding domain of mercuric ion reductase, removes Hg2+ from proteins, delivers it to the catalytic core, and protects cells under glutathione-depleted conditions. Biochemistry, 44, 11402–11416.

    Article  CAS  PubMed  Google Scholar 

  • Meredith, J. D., Chapman, I., Ulrich, K., Sebastian, C., Stull, F., & Gray, M. J. (2022). Escherichia coli RclA is a highly active hypothiocyanite reductase. Proceedings of the National Academy of Sciences, 119, e2119368119.

    Article  CAS  Google Scholar 

  • Parker, B. W., Schwessinger, E. A., Jakob, U., & Gray, M. J. (2013). The RclR protein is a reactive chlorine-specific transcription factor in Escherichia coli. Journal of Biological Chemistry, 288, 32574–32584.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schrödinger, L. (2010). The PyMOL molecular graphics system. Version 1.5.

  • Shearer, H. L., Loi, V. V., Weiland, P., Bange, G., Altegoer, F., Hampton, M. B., Antelmann, H., & Dickerhof, N. (2023). MerA functions as a hypothiocyanous acid reductase and defense mechanism in Staphylococcus aureus. Molecular Microbiology, 119, 456–470.

    Article  CAS  PubMed  Google Scholar 

  • Shen, Y., & Buick, R. (2004). The antiquity of microbial sulfate reduction. Earth-Science Reviews, 64, 243–272.

    Article  CAS  Google Scholar 

  • Signat, B., Roques, C., Poulet, P., & Duffaut, D. (2011). Role of Fusobacterium nucleatum in periodontal health and disease. Current Issues in Molecular Biology, 13, 25–36.

    CAS  PubMed  Google Scholar 

  • Yoshida, Y., Ito, S., Kamo, M., Kezuka, Y., Tamura, H., Kunimatsu, K., & Kato, H. (2010). Production of hydrogen sulfide by two enzymes associated with biosynthesis of homocysteine and lanthionine in Fusobacterium nucleatum subsp. nucleatum ATCC 25586. Microbiology, 156, 2260–2269.

    Article  CAS  PubMed  Google Scholar 

  • Yoshihara, T., Kioi, M., Baba, J., Usuda, H., Kessoku, T., Iwaki, M., Takatsu, T., Misawa, N., Ashikari, K., Matsuura, T., et al. (2021). A prospective interventional trial on the effect of periodontal treatment on Fusobacterium nucleatum abundance in patients with colorectal tumours. Scientific Reports, 11, 23719.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (MSIT) (grant NRF-2019M3E5D6063871). This research was also supported by the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET), funded by the Ministry of Agriculture, Food and Rural Affairs (MAFRA) (321036053HD020).

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YB and NCH designed the research. YB, JR, and JHP conceived and performed the experiments. SJ, IJ and NCH provided expertise and feedback. YB, JR, and NCH wrote the manuscript, and NCH secured funding.

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Correspondence to Inseong Jo or Nam-Chul Ha.

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Shin, H., Baek, Y., Lee, D. et al. Structural and Functional Analyses of the Flavoprotein Disulfide Reductase FN0820 of Fusobacterium nucleatum. J Microbiol. 61, 1033–1041 (2023). https://doi.org/10.1007/s12275-023-00095-9

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  • DOI: https://doi.org/10.1007/s12275-023-00095-9

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