INTRINSIC PENICILLIN RESISTANCE IN ENTEROCOCCI

Penicillin resistance development in enterococci has been associated w ith 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 res istant mutants of Enterococcus hirae ATCC 9790 the low-affinity PBP (P BP5) overproduction was associated with a deletion in a genetic elemen t, located 1 kb upstream of the pbp5 gene, which negatively controlled PBP5 synthesis, Hypersusceptibility to penicillin was associated with a point mutation in the pbp5 gene, which causes premature termination of translation, Structural homologies between low-affinity PBPs of th e different enterococcal species have been suggested by cross-reactivi ty of antibodies raised against E, hirae PBP5 with PBP5 of Enterococcu s faecium and Enterococcus faecalis. Acquisition of a high-level ampic illin resistance in E, faecium was associated with overproduction of P BP5, which, compared with PBP5 of moderately resistant strains, appear ed to be modified in its penicillin-binding capability, The modified p henotype of PBP5 was found to be associated to some amino acid substit utions in the region between the SDN and KTG motifs, In particular, th e substitution converting a polar residue (T) in a nonpolar one (A or I) could play an important role in remodeling the penicillin-binding d omain and determining the decrease in penicillin affinity.