Disease relevance of ampD

• 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 [1].
• To test this possibility, the responses to different inducers of E. coli transformants containing various ampD regions were assessed [2].
• Altered phenotypes associated with ampD mutations in Enterobacter cloacae [2].
• Inactivation of the ampD gene in Pseudomonas aeruginosa leads to moderate-basal-level and hyperinducible AmpC beta-lactamase expression [3].
• The ampD gene product regulates the expression of AmpC beta-lactamase in gram-negative bacteria and is proposed to be involved in peptidoglycan metabolism [4].

High impact information on ampD

• When a chromosomal or plasmid-borne copy of ampD was present, the amount of pentapeptide-containing muropeptides in the cell wall increased upon addition of the cell wall constituent diaminopimelic acid to the growth medium [5].
• Deletion of both genes led to constitutive ampR-dependent overproduction of beta-lactamase, whereas an out-of-frame deletion in AmpD caused the basal expression to increase two-fold [6].
• Since neither AmpD nor AmpE are needed for beta-lactam induction and since these proteins could not be covalently labelled by benzylpenicillin, they are not thought to act as beta-lactam-binding sensory transducers [6].
• Inactivation of AmpD leads to derepression of beta-lactamase expression, presenting a major pathway for the acquisition of constitutive antibiotic resistance [7].
• We constructed an assay system for studying mechanism(s) of enterobacterial ampD mutation using the well-developed genetics of E. coli [8].

Chemical compound and disease context of ampD

• Transformation of the transconjugant E. coli strain with plasmid pNH5 carrying the ampD gene (whose product decreases the level of expression of ampC) resulted in an eightfold decrease in the MIC of cefoxitin [9].
• Tazobactam also had no effect on the accumulation of a key intermediate in the AmpC beta-lactamase induction pathway, 1,6-anhydromurotripeptide, in an ampD mutant strain of E. coli [10].
• Escherichia coli requires AmpD to respond to extracellular signaling amino acids, such as diaminopimelic acid, and this signal transduction system may regulate peptidoglycan composition in response to cell wall turnover products [5].
• Four mutant plasmids derived from pKU403 (pKU404, pKU405, pKU406, and pKU407) were isolated in an AmpD mutant of Escherichia coli ML4953 by selection with ceftazidime or aztreonam [11].

Biological context of ampD

• In some enterobacterial pathogens, but not in Escherichia coli, loss-of-function mutations in the ampD gene are a common route to beta-lactam antibiotic resistance [8].
• The sequences of the ampD genes and promoter regions from these strains were determined and compared to that of wild-type ampD from P. aeruginosa PAO1 [3].
• Construction of a malE-ampD gene fusion allowed purification of biologically active fusion protein by affinity chromatography [12].
• This suggests that the gene products AmpD and AmpE may function in the transduction of external signals. beta-Lactam antibiotics are analogs of cell wall components that can be released during cell wall morphogenesis of enterobacteria [5].
• It is suggested that the negative regulatory effect of AmpD is due to the hydrolysis of anhydro-muropeptides which may function as signals for beta-lactamase induction [12].

Associations of ampD with chemical compounds

• In the presence of wild-type ampD, transformants responded equally to cefoxitin and cefotetan, regardless of temperature [2].
• In the presence of temperature-sensitive ampD, induction by cefotetan was similar to that by cefoxitin at 30 degrees C but greater than that by cefoxitin at 42 degrees C. These results suggest that ampD encodes a protein involved in induction of AmpC beta-lactamase in E. cloacae [2].
• Indeed, MICs of cefepime and cefpirome remained 10 times higher than those for a stable derepressed clinical isolate (OUDhyp) transformed with an ampD gene [13].
• Of the 12 ceftazidime-resistant E. cloacae NOR-1 strains, 3 had AmpD proteins with amino acid changes, while the others had truncated AmpD proteins [14].

References