An rfuABCD-Like Operon and Its Relationship to Riboflavin Utilization and Mammalian Infectivity by Borrelia burgdorferi

Infect Immun. 2021 Sep 16;89(10):e0030721. doi: 10.1128/IAI.00307-21. Epub 2021 Jul 12.


Riboflavin is an essential micronutrient, but its transport and utilization have remained largely understudied among pathogenic spirochetes. Here, we show that Borrelia burgdorferi, the zoonotic spirochete that causes Lyme disease, is able to import riboflavin via products of its rfuABCD-like operon as well as synthesize flavin mononucleotide and flavin adenine dinucleotide despite lacking canonical genes for their synthesis. Additionally, a mutant deficient in the rfuABCD-like operon is resistant to the antimicrobial effect of roseoflavin, a natural riboflavin analog, and is attenuated in a murine model of Lyme borreliosis. Our combined results indicate not only that are riboflavin and the maintenance of flavin pools essential for B. burgdorferi growth but also that flavin utilization and its downstream products (e.g., flavoproteins) may play a more prominent role in B. burgdorferi pathogenesis than previously appreciated.

Keywords: Borrelia burgdorferi; Lyme disease; RfuABCD; riboflavin; roseoflavin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacterial Proteins / genetics*
  • Borrelia burgdorferi / drug effects*
  • Borrelia burgdorferi / genetics*
  • Female
  • Lyme Disease / drug therapy*
  • Lyme Disease / microbiology*
  • Mammals / microbiology
  • Mice
  • Mice, Inbred C3H
  • Operon / genetics*
  • Riboflavin / pharmacology*


  • Bacterial Proteins
  • Riboflavin