AmpR

AmpR is a transcriptional regulatory protein found in many Gram-negative bacteria, most notably in Pseudomonas aeruginosa and members of the Enterobacteriaceae. It governs the expression of the chromosomal AmpC beta-lactamase, an enzyme that confers resistance to many beta-lactam antibiotics. AmpR acts as a key component of the cell’s response to antibiotic exposure and cell-wall turnover.

AmpR function is dual: it can repress or activate ampC transcription depending on signal molecules in the cytoplasm. In the absence of inducers, AmpR binds to the ampC promoter region and maintains low expression. When beta-lactams or cell-wall remodeling generate specific muropeptides, these molecules are imported into the cytoplasm via the AmpG transporter and processed by AmpD; binding of these ligands to AmpR shifts its conformation to an activator form, increasing ampC transcription and beta-lactamase production.

Genetic and biochemical studies show that AmpR activity is intertwined with peptidoglycan recycling pathways and other regulators. Changes in ampR, muropeptide flux, or related genes can alter the level of AmpC and the degree of antibiotic resistance. Because AmpC overproduction reduces beta-lactam susceptibility, AmpR is a focus of research into strategies to counter resistance, including inhibitors of AmpR signaling or interference with the muropeptide recycling pathway.

AmpR homologs are widespread in Gram-negative pathogens; while the core mechanism of AmpC regulation is conserved, individual species show variations in regulatory strength and target genes.