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

J Microbiol. 2023 Dec;61(12):1033-1041. doi: 10.1007/s12275-023-00095-9. Epub 2023 Dec 20.

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.

Keywords: 5-hydroxytryptophan; Flavoprotein disulfide reductase; Fusobacterium; L-tryptophan; Oxygen reduction; RclA.

MeSH terms

  • Bacteria / metabolism
  • Escherichia coli* / genetics
  • Escherichia coli* / metabolism
  • Flavoproteins / chemistry
  • Flavoproteins / metabolism
  • Fusobacterium nucleatum*
  • Humans
  • Mouth

Substances

  • Flavoproteins