Siderophores are low molecular weight, high affinity
iron chelating molecules that are essential
virulence factors in many Gram-negative bacterial pathogens. Whereas the chemical structure of
siderophores is extremely variable, the function of
siderophores has been narrowly defined as the chelation and delivery of
iron to bacteria for proliferation. The discovery of the host
protein Lipocalin 2, capable of specifically sequestering the
siderophore Enterobactin but not its glycosylated-derivative
Salmochelin, indicated that diversity in structure could be an immune evasion mechanism that provides functional redundancy during
infection. However, there is growing evidence that
siderophores are specialized in their
iron-acquisition functions, can perturb
iron homeostasis in their hosts, and even bind non-
iron metals to promote bacterial fitness. The combination of
siderophores produced by a pathogen can enable inter-bacterial competition, modulate host cellular pathways, and determine the bacterial "replicative niche" during
infection. This review will examine both classical and novel functions of
siderophores to address the concept that
siderophores are non-redundant
virulence factors used to enhance bacterial pathogenesis.