The Human Innate Immune Protein Calprotectin Elicits a Multimetal Starvation Response in Pseudomonas aeruginosa

The study examined the effects of the human innate immune protein calprotectin (CP) on Pseudomonas aeruginosa, focusing on its ability to induce a multimetal starvation response by sequestering essential metals such as iron (Fe), zinc (Zn), and manganese (Mn). CP treatment led to a robust Zn starvation response, characterized by the upregulation of Zn uptake systems, while the Fe response was incomplete. Despite CP's ability to sequester Mn, no significant Mn starvation response was observed. The study also found that CP treatment increased the expression of membrane-remodeling proteins, enhancing tolerance to polymyxin B, an antimicrobial peptide. These responses were distinct from those observed under single-metal limitations, suggesting that CP's multimetal withholding elicits a complex microbial response that affects P. aeruginosa's virulence potential. The research highlighted the intricate relationship between metal homeostasis and pathogen virulence.