Metal sequestration by S100 proteins in chemically diverse environments

During infection, the mammalian host initiates a metal-withholding response against invading microbial pathogens to inhibit their growth and survival, a process often termed 'nutritional immunity'. The host-defense S100 proteins calprotectin (CP) (S100A8/S100A9 oligomer), S100A12, and S100A7 play key roles in the innate immune response by sequestrating essential transition metal nutrients from microbes in the extracellular space. Accumulating evidence suggests that the antimicrobial activity of these proteins varies between infection sites and may be affected by the local chemical environment. Herein, we discuss the interplay between host metal-withholding proteins and microbial pathogens in the context of the chemical complexity of infection sites and highlight recent advances in our understanding of how chemically diverse conditions affect the properties and functions of S100 proteins.