Intrinsic Penicillin Resistance in Enterococci

<jats:title>ABSTRACT</jats:title> <jats:p> Penicillin resistance development in enterococci has been associated with overproduction of a low-affinity penicillin-binding protein (PBP) that is a normal component of the PBP pattern of these bacteria and is apparently able to substitute the functions of the other PBPs. In resistant mutants of <jats:italic toggle="yes">Enterococcus hirae</jats:italic> ATCC 9790 the low-affinity PBP (PBP5) overproduction was associated with a deletion in a genetic element, located 1 kb upstream of the <jats:italic toggle="yes">pbp5</jats:italic> gene, which negatively controlled PBP5 synthesis. Hypersusceptibility to penicillin was associated with a point mutation in the <jats:italic toggle="yes">pbp5</jats:italic> gene, which causes premature termination of translation. Structural homologies between low-affinity PBPs of the different enterococcal species have been suggested by cross-reactivity of antibodies raised against <jats:italic toggle="yes">E. hirae</jats:italic> PBP5 with PBP5 of <jats:italic toggle="yes">Enterococcus faecium</jats:italic> and <jats:italic toggle="yes">Enterococcus faecalis</jats:italic> . Acquisition of a high-level ampicillin resistance in <jats:italic toggle="yes">E. faecium</jats:italic> was associated with over-production of PBP5, which, compared with PBP5 of moderately resistant strains, appeared to be modified in its penicillin-binding capability. The modified phenotype of PBP5 was found to be associated to some amino acid substitutions in the region between the SDN and KTG motifs. In particular, the substitution converting a polar residue (T) in a nonpolar one (A or I) could play an important role in remodeling the penicillin-binding domain and determining the decrease in penicillin affinity. </jats:p>