Table 1.

Host and bacterial factors involved in iron and zinc exploitation.

Iron	Protein Type	Localization	Function	Reference
Host sources of iron	Heme containing proteins	Cell membranes, Cytoplasm	Transport electrons and oxygen during respiration	203
	Transferrin	Blood, interstitial fluid	Sequester iron in blood and interstitial fluid	65,203
	Lactoferrin	Secretory fluids	Sequester iron in secretory fluids	58
	Ferritin	Cytoplasm	Store iron to balance intracellular iron concentrations	100
	labile iron pool	Cytoplasm	Buffer intracellular iron concentrations	204
Iron acquisition systems	Membrane receptors	Cell membranes	Actively transport iron from the environments	205
	ABC transporters	Cell membranes	Actively transport iron from the environments	206
	Siderophores	Secreted	Chelates iron with high affinity	207–209
Utilization of acquired iron	Heme biosynthesis	Cytoplasm	Transport electrons and bind diatomic gases in respiration, defend oxidative stress	210
	Iron-sulfur protein biosynthesis	Cytoplasm	Synthesize dNTPs, produce energy, and defend against oxidative stress	211
Zinc	Protein Type	Localization	Function	Reference
Host sources of zinc	Metallothioneins	Cytoplasm	Zinc buffering, suppress inflammatory cytokine secretion	32,212
	Zincosomes	Cytoplasm	Zinc storage and buffering	33
	Metalloproteinases	Cytoplasm, membrane, and secreted	Degrade extracellular matrix, direct cellular differentiation and tissue morphogenesis	213–215
	Calprotectin	Cytoplasm – secreted by neutrophils	Chelate zinc and manganese at site of infection	71
	S100 proteins	Cytoplasm – secreted by neutrophils	Regulate cell proliferation and differentiation. Chelate metals at site of infection	216
	Zinc fingers	Cytoplasm/nucleus	Transcription factors, nucleases, polymerases, ribosomes	217,218
	Serum albumin	Blood, interstitial fluid	Maintain osmotic pressure, carry metabolites	219
	α-2-macroglobulin	Blood	Inhibits bacterial proteases via entrapment	220
Zinc acquisition systems	ZIP (Zrt-Irt-like protein)	Cell Membrane	Diffusion	140
	Znu (ABC)	Cell Membrane	Active Transport	13
	Zincophores	Secreted	Putatively bind zinc for transport	221
	Calprotectin Binding Protein	Secreted	Binds calprotectin for transport	131
Utilization of zinc during pathogenesis	Metalloproteases	Secreted	Compromise epithelial and endothelial barriers, interfere with clotting cascade, cleave immune proteins to evade clearance.	146,149,222