Penicillin-binding protein 3SAL (PBP3SAL)

Penicillin-binding protein 3SAL (PBP3SAL) is a specialized, pathogen-specific enzyme in Salmonella enterica that functions as a peptidoglycan transpeptidase to promote bacterial cell division. Unlike the canonical PBP3 (FtsI) found in most enteric bacteria, PBP3SAL is specifically adapted to function in acidic environments, such as the lumen of the Salmonella-containing vacuole (SCV) within host phagocytes. It is highly upregulated during intracellular infection and can replace the function of the canonical PBP3, which is typically downregulated or inactive under acidic conditions. Crucially, PBP3SAL exhibits low affinity for many first-line beta-lactam antibiotics like ceftriaxone, allowing the pathogen to persist and cause clinical relapses even after treatment with drugs that are effective against extracellular bacteria. Recent studies have identified cefotiam as an antibiotic with high affinity for PBP3SAL, highlighting the protein as a critical target for developing more effective therapies against intracellular Salmonella infections and preventing disease recurrence.

Other names

STM1836SL1344_1765Alternative penicillin-binding protein 3Pathogen-specific PBP3Acid-active peptidoglycan synthaseftsI paralog

Inhibition of transpeptidation during peptidoglycan synthesis, leading to the blockage of bacterial cell division and subsequent cell death or filamentation.