ampG

AmpG is a bacterial inner membrane permease encoded by the ampG gene. It participates in the peptidoglycan recycling pathway in many Gram-negative bacteria by transporting anhydro-muropeptides, released from the cell wall, from the periplasm into the cytoplasm. This transport is a key step linking cell wall turnover to the regulation of beta-lactamase expression.

Substrates and pathway: During cell wall remodeling, muropeptides are generated. The enzyme NagZ trims these fragments to produce 1,6-anhydro-muropeptide signals that are imported into the cytoplasm by AmpG. In the cytoplasm, the AmpR transcriptional regulator senses muropeptide levels and modulates the expression of ampC beta-lactamase. Elevated AmpC production enables bacteria to hydrolyze beta-lactam antibiotics, contributing to antibiotic resistance.

Genetic context and significance: AmpG is commonly found in operons with ampD and ampR, forming a regulatory module for inducible AmpC expression. Disruption or loss of AmpG function can reduce or abolish inducible AmpC production, potentially lowering beta-lactam resistance. TheAmpG permease is broadly distributed among Gram-negative pathogens, including Escherichia coli and Pseudomonas aeruginosa.

Structure and research: AmpG is predicted to be a multi-pass inner membrane protein with several transmembrane helices. Although precise structural details remain unresolved, functional studies using genetics and transport assays support its role as the muropeptide importer that connects peptidoglycan recycling to antibiotic resistance mechanisms. As such, AmpG is of interest in considerations of strategies to mitigate beta-lactam resistance.