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

ABSTRACT: β-lactam antibiotics are widely used to treat bacterial infections, yet treatment failures frequently occur even without resistance. Here, we show that the innate immune protein calprotectin (CP), released by neutrophils and abundant at infection sites, induces tolerance to β-lactam antibiotics in Staphylococcus aureus. CP is a potent zinc chelator and was found to inhibit the activity of S. aureus autolysins, zinc-dependent enzymes essential for bacterial lysis following β-lactam-mediated inhibition of cell wall synthesis. This protection was independent of bacterial growth or metabolism and was specific to β-lactam antibiotics. Mechanistically, CP inactivated the amidase activity of Atl, the major S. aureus autolysin, through zinc sequestration. In vivo, oxaci

SUBMITTER: Velez AZ 

PROVIDER: S-EPMC12132314 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature