Calprotectin-mediated survival of <i>Staphylococcus aureus</i> in coculture with <i>Pseudomonas aeruginosa</i> occurs without nutrient metal sequestration

The current working model that describes how the innate immune protein calprotectin (CP) protects the host against bacterial pathogens focuses on its capacity to sequester multiple essential metal nutrients in a process called nutritional immunity. Our study further explores this function by focusing on the effects of metal availability and CP treatment on the dynamics of <i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i> grown in coculture. These two bacterial pathogens are of significant clinical concern and colocalize with CP at infection sites. This work reveals that CP modulates <i>P. aeruginosa/S. aureus</i> coculture dynamics in a manner that is independent of its ability to sequester nutrient metal ions. This surprising result is important because it demonstrates that CP has metal-independent function and thus contributes to the host-pathogen and pathogen-pathogen interactions in ways that are not accounted for in the current working model focused on metal sequestration.