Overview on the Bacterial Iron-Riboflavin Metabolic Axis

Abstract

Redox reactions are ubiquitous in biological processes. Enzymes involved in redox metabolism often use cofactors in order to facilitate electron-transfer reactions. Common redox cofactors include micronutrients such as vitamins and metals. By far, while iron is the main metal cofactor, riboflavin is the most important organic cofactor. Notably, the metabolism of iron and riboflavin seem to be intrinsically related across life kingdoms. In bacteria, iron availability influences expression of riboflavin biosynthetic genes. There is documented evidence for riboflavin involvement in surpassing iron-restrictive conditions in some species. This is probably achieved through increase in iron bioavailability by reduction of extracellular iron, improvement of iron uptake pathways and boosting hemolytic activity. In some cases, riboflavin may also work as replacement of iron as enzyme cofactor. In addition, riboflavin is involved in dissimilatory iron reduction during extracellular respiration by some species. The main direct metabolic relationships between riboflavin and iron in bacterial physiology are reviewed here.

Predicting Vibrio cholerae infection and disease severity using metagenomics in a prospective cohort study

“…All three Bifidobacterium species associated with contacts that developed infection were also associated with asymptomatic rather than symptomatic disease ( Figure 3 ), and prior work on this genera supports several hypotheses for this relationship. First, Bifidobacteria are known to produce the SCFA acetate that can protect against enteric infection in mice (33,34)(30). SCFAs are also known to inhibit cholera toxin-related chloride secretion in the mouse gut, reducing water and sodium loss, and have also been observed to increase cholera toxin-specific antibody responses (31–33).…”

“…For example, several gene families involved in iron transport, iron regulation, and riboflavin conversion appeared among the top twenty features associated with uninfected and asymptomatic individuals, suggesting that competition for iron might be a protective mechanism of the gut microbiota against V. cholerae , as is the case for other pathogens (7). Iron is often a limiting redox cofactor in the gut, and bacteria have evolved strategies to solubilize and internalize iron (34,35). Riboflavin (another major redox cofactor in bacteria) and iron levels are reciprocally regulated in V. cholerae , and more generally, riboflavin may allow V. cholerae to overcome iron limitation in the gut (34,36).…”

“…Iron is often a limiting redox cofactor in the gut, and bacteria have evolved strategies to solubilize and internalize iron (34,35). Riboflavin (another major redox cofactor in bacteria) and iron levels are reciprocally regulated in V. cholerae , and more generally, riboflavin may allow V. cholerae to overcome iron limitation in the gut (34,36). A gut microbiota more competitive for iron could be an important factor in resistance to V. cholerae colonization or virulence.…”

Genome-scale exploration of transcriptional regulation in the nisin Z producer Lactococcus lactis subsp. lactis IO-1

“…www.nature.com/scientificreports www.nature.com/scientificreports/ proteins [68][69][70] . These findings open the possibility for divergent regulatory mechanisms and suggest that there is still a long way to fully characterize riboflavin biosynthesis regulation mechanisms.…”

Extracellular Electron Transfer: Respiratory or Nutrient Homeostasis?

“…Many Gram-positive bacteria, including E. faecalis (12) and Listeria monocytogenes (13), are known to be able to reduce extracellular ferric iron. Reduction of extracellular ferric iron is believed to be a common strategy to enhance iron bioavailability and iron uptake in both prokaryotes and eukaryotes (14,15). This then raises the question of whether EET functions in nutrient uptake (e.g., iron bioavailability) at an energy cost or in respiration, aiding in the production of energy.…”