FtsI

FtsI, also known as penicillin-binding protein 3 (PBP3), is a bacterial enzyme that belongs to the family of penicillin-binding proteins. It is a class B transpeptidase responsible for the final cross-linking step in peptidoglycan synthesis during cell division, contributing to septal peptidoglycan formation as the cell constricts.

In many Gram-negative bacteria, FtsI is a core component of the divisome, a multi-protein complex that coordinates cytokinesis. It localizes to the division site in concert with the FtsZ-derived Z-ring and other divisome proteins, such as FtsW, FtsQ, FtsL, FtsB, and FtsN. FtsI provides the transpeptidase activity required to cross-link peptide side chains in the septal peptidoglycan, while glycan strand synthesis is carried out by other enzymes, notably class A PBPs.

FtsI is essential for proper cell division in many bacteria; loss or inhibition of its activity typically results in filamentous cells that fail to complete septation. The enzyme is a target of β-lactam antibiotics, which inhibit its transpeptidase activity and disrupt septum formation. Some β-lactams are noted for relatively high affinity toward PBP3, contributing to their bactericidal effects via division arrest rather than immediate lysis.

Resistance to FtsI-targeting antibiotics can arise through mutations in ftsI that reduce drug binding, as well as through canonical mechanisms such as β-lactamase production, reduced permeability, and efflux. FtsI homologs are found across diverse bacterial species and are commonly referred to as PBP3 in those organisms.