The study shows that the human antimicrobial peptide LL-37 can grab onto hidden iron‑stealing molecules (stealth siderophores) that some bacteria use to become more dangerous. When LL-37 binds these molecules, it folds into a more active shape, and the attraction is mainly due to electric charges. This suggests LL-37 helps the immune system mop up bacterial iron‑chelation tools, adding another layer to how our bodies fight infection.

A growing number of evidence shows that human-associated microbiota is an important contributor in health and disease. However, much of the complexity of host-microbiota interaction remains to be elucidated both at cellular and molecular levels. Siderophores are chemically diverse, ferric-specific chelators synthesized and secreted by microbes to secure their iron acquisition. The host defense peptide LL-37 is ubiquitously produced at epithelial surfaces modulating microbial communities and suppressing pathogenic strains. The present work demonstrates that LL-37 binds tightly siderocalin-resistant stealth siderophores which are important contributors to the virulence of several pathogens. As indicated by circular dichroism spectroscopic experiments, addition of aerobactin and rhizoferrin increases the membrane active α-helical conformation of the partially folded peptide. The cationic nature of LL-37 (+6 net charge at pH 7.4) and the multiple carboxylate groups present in siderophores refer to the dominant contribution of electrostatic interactions in the stabilization of peptide-chelator adducts. It is proposed that aside siderocalin proteins, LL-37 may be a complementary, less specific component of the siderophore scavenging repertoire of the innate immune system.