Siderocalin (Lcn 2) Also Binds Carboxymycobactins, Potentially Defending against Mycobacterial Infections through Iron Sequestration

摘要: Siderocalin, a member of the lipocalin family binding proteins, is found in neutrophil granules, uterine secretions, and at markedly elevated levels serum synovium during bacterial infection; it also secreted from epithelial cells response to inflammation or tumorigenesis. Identification high-affinity ligands, catecholate-type siderophores (such as enterochelin), suggested possible function for siderocalin: an antibacterial agent, complementing general antimicrobial innate immune system iron-depletion strategy, sequestering iron ferric siderophore complexes. Supporting this hypothesis, siderocalin potent bacteriostatic agent vitro under iron-limiting conditions and, when knocked out, renders mice remarkably susceptible infection. Here we show that binds soluble mycobacteria, including M. tuberculosis: carboxymycobactins. Siderocalin employs degenerate recognition mechanism cross react with these dissimilar types siderophores, broadening potential utility defense.