Disease relevance of ampD

• Therefore, a model system was designed to determine the effect of ampD mutations on ceftazidime MICs using an AmpD(-) mutant Escherichia coli strain which produced an inducible plasmid-encoded AmpC. ampD genes were amplified by PCR from strains of E. coli, Citrobacter freundii, and Pseudomonas aeruginosa [1].
• Escherichia coli JRG582 is an ampD ampE deletion derivative of strain HfrH and accordingly it is derepressed for expression of the cloned inducible beta-lactamase gene of Citrobacter freundii, carried on plasmid pNU305 [2].
• The inducible phenotype was dependent on the E. coli ampD and ampG gene products [3].

High impact information on ampD

• In contrast, the ampD mutant accumulates a novel cell wall muropeptide, 1,6-anhydro N-acetylmuramyl-L-alanyl-D-glutamyl-meso-diaminopimelic acid (anhMurNAc-tripeptide), in its cytoplasm [4].
• Mutations within the structural gene of ampD can lead to AmpC overproduction and increases in beta-lactam MICs in organisms with an inducible ampC [1].
• However, ampD truncation products and ampD from a partially derepressed P. aeruginosa strain resulted in ceftazidime MICs of >256 microg/ml, indicating a role for these gene modifications in derepressed phenotypes [1].
• The alternative mechanism involved in the derepressed phenotype of the C. freundii isolate was downregulation of ampD transcription [1].

References