An unexpected benefit from E. coli: how enterobactin benefits host health.

Aileen K Sewell,Min Han,Bin Qi

doi:10.15698/mic2018.10.653

Aileen K Sewell, Min Han + Show 1 more

Open Access

https://doi.org/10.15698/mic2018.10.653

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Abstract

Iron plays many critical roles in human biology, such as aiding the transport of oxygen and mediating redox reactions. Iron is essential for life, yet little is known about how iron is taken up into mitochondria to impact the labile iron pool. Iron deficiency is one of the most prevalent human nutrient-deficiency diseases in the world and is a major cause of anemia that affects >25% of the world’s population, but unfortunately the current treatment (oral iron supplementation) is inefficient and has many side effects. A greater understanding of iron uptake, and discovery of molecules that aid in this process, may lead to more effective treatments for iron deficiency. In this study, we uncovered a unique and surprising role for an Escherichia coli-produced siderophore enterobactin (Ent) that facilitates iron uptake by the host, observed in both C. elegans and mammalian cells. Although siderophores are well-known Fe+3 scavengers, this activity has previously been described to only benefit iron acquisition by bacteria, not the host. This unexpected function is dependent on the binding of Ent to the host’s ATP synthase α-subunit but is independent of other subunits of the ATP synthase. This finding marks a major shift regarding the role of this siderophore in the “iron tug-of-war” paradigm, which is often used to describe the fight between the bacteria and the host for this essential micronutrient. Instead, this study presents E. coli as a commensal “friend” that provides a molecule that supports the host’s iron homeostasis. This work reveals a novel, beneficial role of a bacteria-generated molecule in aiding the host’s iron homeostasis, and points to surprising new benefits from commensal bacteria.

Highlights

Extensive studies in the microbiota field have clearly indicated a symbiotic relationship between a multitude of commensal bacteria and their animal hosts
Beneficial role for Enterobactin in host health was necessary for growth under our assay condition, it was not absolutely required when worms were well-fed on Entdeficient bacteria (Figure 1D)
Through an affinity purification screen, we further found that bacterial Ent binds to the α-subunit of the ATP synthase in the host (ATP-1 in C. elegans, ATP5A1 in mammalian cells)

Summary

Introduction

Extensive studies in the microbiota field have clearly indicated a symbiotic relationship between a multitude of commensal bacteria and their animal hosts. We uncovered a unique and surprising role for an Escherichia coliproduced siderophore enterobactin (Ent) that facilitates iron uptake by the host, observed in both C. elegans and mammalian cells. Siderophores are well-known Fe+3 scavengers, this activity has previously been described to only benefit iron acquisition by bacteria, not the host.

Results

Conclusion