AmpC+Beta-Lactamases

The AmpC beta-lactamase of //Escherichia coli// was the first bacterial enzyme reported to destroy penicillin in 1940 (Jacoby, 2009). It is coded for by the //ampC// gene.

Most beta-lactamases are cephalosporinases, though they are capable of hydrolysing all beta-lactams to some extent (Hanson, 2003).

__**Distribution:**__ The recent rise in the number of sequenced bacterial genes and genomes has led to the discovery of many chromosomal AmpC beta-lactamases, across a diverse range of bacteria. A putative list of known AmpC beta-lactamases, from Jacoby (2009) is shown below. However, as the author himself states, it is undoubtedly incomplete.

It is worth noting that sequence alone is not sufficient to differentiate an AmpC beta-lactamase from the ubiquitous low weight penicillin binding proteins involved in cell wall biosynthesis. Indeed, both have the same general structure and share conserved sequence motifs near the serine residue in the active site. However, the AmpC name itself is also not a reliable indicator of AmpC beta-lactamase activity, since several enzymes so labeled in the literature actually belong to the Class A, rather than the Class C......

The table below is hence based on proteins with the requisite structure, from organisms from organisms that have been demonstrated to possess the appropriate AmpC-type beta-lactamase activity.



__**AmpC Beta-Lactamases in E. coli**__

E. coli produces a Beta-lactam binding protein, AmpH, which is related to AmpC structurally, but lacks Beta-lactamase activity (Jacoby, 2009).

__**Physical Properties**__

Typical physical properties of AmpC Beta-lactamases are listed below:
 * Molecular mass between 34 and 40 kDa
 * Isoelectric point >8.0
 * Located in bacterial periplasm (except in //P. immobilis// where secreted)
 * Active on penicillins, very active on cephalosporins and can hydrolyse cephamycins, oxyiminocephalosporins and monobactams though at a very reduced rate (<1% of benzylpenicillin)

AmpC enzymes are thought to have evolved to maximal effficiency, due to the fact that the turnover rate has been shown to be diffusion limited rather than catalysis limited with preferred substrates in //E. cloacae//.

__**Clinical Importance**__

AmpC beta-lactamases have been found to interfere with Extended Spectrum Beta-LActamase (ESBL) confirmatory tests. Indeed, positive ESBL screens may be due to AmpC beta-lactamases more often than ESBLs. This causes a risk to patients, since false positive ESBL screens would incorrectly indicate susceptibility of ESBLs to cephalosporins. Hence, the production of AmpC by an organism necessitates the use of a more reliable ESBL confirmatory test (Munier et al, 2010).