β- lactamases are of primary importance. In addition to the production of β- lactamases resistance can also be due to possession of altered PBPs. Since β- lactams cannot bind as effectively to these altered PBPs, the antibiotic is less effective at disrupting cell wall synthesis. The PBPs are thought to be the ancestors of the naturally occurring chromosomally mediated β- lactamase in many bacterial genera.
The first plasmid-mediated β- lactamase in Gram-negatives, TEM-1, was described in the early 1960s. At present over 500 chromosomal, plasmid and transposon located β- lactamases are known