= Calprotectin
\b[Calprotectin] is a <protein> complex composed of the <S100A8> and <S100A9> <protein subunits>. It is abundant in <neutrophils> and can restrict microbial access to <manganese> and <zinc> through metal binding. This is an example of <nutritional immunity>: changing nutrient availability can impair microbial functions without directly cutting apart the microorganism.<Nutrient metal sequestration by calprotectin inhibits bacterial superoxide defense, enhancing neutrophil killing of Staphylococcus aureus by Thomas E. Kehl-Fie and others>[Introduction, S100A8/S100A9 complex; Summary, metal sequestration and host defense]{ref}
A primary study compared ordinary calprotectin with a variant defective in its transition-metal-binding sites. <Isothermal titration calorimetry> tested binding, while growth and enzyme-activity assays tested functional consequences. Loss of metal binding strongly reduced antimicrobial activity; manganese add-back restored an affected bacterial <superoxide dismutase> activity. These comparisons linked metal availability to the phenotype rather than relying on calprotectin abundance alone.<Nutrient metal sequestration by calprotectin inhibits bacterial superoxide defense, enhancing neutrophil killing of Staphylococcus aureus by Thomas E. Kehl-Fie and others>[Figure2, binding and mutant comparison; Figure3, bacterial enzyme activity and metal add-back]{ref}
An original one-metal model separates total from free metal:
$$
[M]_{\mathrm{total}}=[M]_{\mathrm{free}}+[PM].
$$
If the stipulated system contains $1.0\,\mathrm{\mu M}$ metal and $0.8\,\mathrm{\mu M}$ is protein-bound, $0.2\,\mathrm{\mu M}$ remains free. The total metal concentration has not changed, although its availability has. Other ligands and competing metals would require additional terms.
Calprotectin therefore illustrates how a host protein can alter a microbe's chemical environment. Its metal-binding behavior depends on conditions and should not be reduced to a universal fixed number of ions bound in every sample; neither the simplified balance nor the presence of the protein alone determines an organism's response.
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