AmpRAmpC

AmpRAmpC refers to the regulatory system that controls the expression of AmpC beta-lactamase in many Gram-negative bacteria. AmpC is a class C beta-lactamase that hydrolyzes a broad range of beta-lactam antibiotics, including penicillins and cephalosporins. In many species, ampC is encoded chromosomally and its expression is inducible. The AmpRAmpC module centers on the transcriptional regulator AmpR and the ampC gene, and is modulated by cell wall turnover products and related recycling pathways.

Mechanism: Under normal conditions, AmpR maintains low or basal AmpC expression. Peptidoglycan turnover generates muropeptides; these are transported by AmpG into the cytoplasm and processed by enzymes such as NagZ; the resulting signaling molecules influence AmpR activity. When beta-lactam antibiotics inhibit cell wall synthesis, damaged peptidoglycan leads to accumulation of activating muropeptides, converting AmpR from a repressor to an activator and upregulating ampC transcription. This results in increased AmpC production and enhanced resistance. In some bacteria, inactivating mutations in AmpD or alterations in muropeptide recycling can cause constitutive, high-level AmpC expression independent of antibiotics.

Spread and variants: Some AmpC genes are carried on plasmids (pAmpC), which can propagate between species and may be expressed independently of AmpR regulation, contributing to higher resistance. Others maintain chromosomal regulation via AmpR and related recycling enzymes. The AmpRAmpC system is clinically relevant because inducible ampC can undermine beta-lactam therapy and complicate susceptibility testing.

Examples: Notable organisms with AmpR-AmpC regulation include Pseudomonas aeruginosa, Enterobacter cloacae, Citrobacter freundii, and Serratia species. Ongoing research investigates regulatory variations and the impact on treatment outcomes.