Siderophore-mediated iron acquisition and modulation of host-bacterial interactions

- Resident bacteria secrete siderophores to compete for iron in the gut.
- Different siderophores enable bacterial niche formation at unique host sites.
- Bacterial siderophores modulate cellular iron homeostatis and host immunity.
- Siderophores enhance pathogen exclusion and limit pro-oxidant mucosal responses.
- Thus siderophores likely influence microbially-driven pathological processes.

Iron is an essential micronutrient for most life forms including the majority of resident bacteria of the microbiota and their mammalian hosts. Bacteria have evolved numerous mechanisms to competitively acquire iron within host environments, such as the secretion of small molecules known as siderophores that can solubilize iron for bacterial use. However, siderophore biosynthesis and acquisition is not a capability equally harbored by all resident bacteria. Moreover, the structural diversity of siderophores creates variability in the susceptibility to host mechanisms that serve to counteract siderophore-mediated iron acquisition and limit bacterial growth. As a result, the differential capabilities to acquire iron among members of a complex microbial community carry important implications for the growth and function of resident bacteria. Siderophores can also directly influence host function by modulating cellular iron homeostasis, further providing a mechanism by which resident bacteria may influence their local environment at the host-microbial interface. This review will explore the putative mechanisms by which siderophore production by resident bacteria in the intestines may influence microbial community dynamics and host-bacterial interactions with important implications for pathogen- and microbiota-driven diseases including infection, inflammatory bowel diseases and colorectal cancer.

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