Clavulanic Acid - Mechanism of Action

Mechanism of Action

Clavulanic acid has negligible intrinsic antimicrobial activity, despite sharing the β-lactam ring that is characteristic of β-lactam antibiotics. However, the similarity in chemical structure allows the molecule to interact with the enzyme β-lactamase secreted by certain bacteria to confer resistance to β-lactam antibiotics. Clavulanic acid is a suicide inhibitor, covalently bonding to a serine residue in the active site of the β-lactamase. This restructures the clavulanic acid molecule, creating a much more reactive species that is attacked by another aminoacid in the active site, permanently inactivating it, and thus inactivating the enzyme.
This inhibition restores the antimicrobial activity of β-lactam antibiotics against lactamase-secreting resistant bacteria. Despite this, some bacterial strains that are resistant even to such combinations have emerged.

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