The innate immune protein calprotectin ablates the bactericidal activity of β-lactam antibiotics.

ABSTRACT: β-lactam antibiotics are among the most widely used treatments for bacterial infections, yet therapeutic failure is common even when no genetic resistance is detected. Understanding how host factors influence antibiotic efficacy is critical for improving outcomes. Here, we identify a host-derived mechanism of antibiotic tolerance mediated by calprotectin (CP), a zinc-binding protein released in large quantities by neutrophils during infection. We show that CP induces tolerance to β-lactam antibiotics in Staphylococcus aureus by chelating zinc and inactivating autolysins, zinc-dependent enzymes required for cell wall degradation and bacterial lysis following β-lactam treatment. This protective effect was specific to β-lactam antibiotics at concentrations of CP showing minimal impact

SUBMITTER: Velez AZ 

PROVIDER: S-EPMC12818397 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature