A Mammalian Siderophore Synthesized by an Enzyme with a Bacterial Homolog Involved in Enterobactin Production

Siderophores have also been identified in mammals.

“Rather, siderophores have also been identified in mammals (Bao et al., 2010;Devireddy et al., 2010).”

The discovery of putative mammalian siderophores suggests humans may maintain iron homeostasis using mechanisms similar to microbes.

“Finally, the discovery of putative mammalian siderophores suggests that humans might use mechanisms analogous to microbes to maintain iron homeostasis (Bao et al., 2010; Devireddy et al., 2010).”

Lcn2 may contribute to limiting M. tuberculosis by shuttling iron out of macrophages, which is supposed to result from binding of a mammalian siderophore.

“In addition, Lcn2 may contribute to this effect by shuttling iron out of macrophages, which is supposed to result from binding of a mammalian siderophore (211, 212).”

Higher organisms such as fungi or mammals are able of producing this type of iron-scavenging molecules.

“Interestingly, also higher organisms such as fungi or mammals are able of producing this type of iron-scavenging molecules [120,121,122].”

Some mammalian siderophores such as catechols are probably synthesized from commensal metabolites or dietary precursors.

“While some of these compounds such as citrate are ubiquitous substrates, other mammalian siderophores such as catechols are probably synthesized from commensal metabolites or dietary precursors [11, 50, 252].”

Lcn2 delivers bacterial and mammalian siderophore-bound iron to the Lcn2 receptor on host cells, suggesting it modulates iron trafficking during infection.

“Lcn2 delivers bacterial as well as mammalian siderophore-bound Fe [131,132] to the Lcn2 receptor expressed by host cells, suggesting that it modulates Fe trafficking and hence Fe metabolism during infection (Fig 2).”

Silencing of the Bdh2 gene leads to siderophore depletion and results in an accumulation of intracellular iron and heme deficiency.

“Silencing of the Bdh2 gene leads to siderophore depletion and results in an accumulation of intracellular iron and heme deficiency”

2,5-DHBA shuttles intracellular labile iron, protects from oxidative stress and is involved in the import of iron into mitochondria.

“2,5-DHBA is meant to shuttle intracellular labile iron, protects from oxidative stress and is involved in the import of iron into mitochondria”

Mammalians produce catechol-like siderophores including 2,5-dihydroxybenzoic acid (2,5-DHBA).

“Siderophores are not limited to microbes as mammalians produce catechol like siderophore including, 2,5-dihydroxybenzoic acid (2,5-DHBA)”

BDH2 is a functional homologue of bacterial EntA in eukaryotes that catalyzes an enzymatic reaction leading to the synthesis of 2,5-DHBA.

“An enyzme called BDH2 (for butyrate dehydrogenase type 2) is a functional homologue of the bacterial EntA in eukaryotes that catalyzes an enzymatic reaction leading to the synthesis of 2,5-DHBA.”

Lcn2 binds siderophores such as enterobactin and delivers Lcn2-Fe-siderophore complexes to host cells through the Lcn2 receptor, blocking bacterial uptake of iron-laden siderophores.

“Lcn2 binds siderophores such as enterobactin and delivers Lcn2-Fe-siderophore complexes to host cells via the Lcn2 receptor (88, 89), inhibiting bacterial uptake of Fe-laden siderophores (87, 90).”