MODIFICATION OF PENICILLIN-BINDING PROTEIN-5 ASSOCIATED WITH HIGH-LEVEL AMPICILLIN RESISTANCE IN ENTEROCOCCUS-FAECIUM

High-level ampicillin resistance in Enterococcus faecium has been show n to be associated with the synthesis of a modified penicillin-binding protein 5 (PBP 5) which had apparently lost its penicillin-binding ca pability (R. Fontana, M. Aldegheri, M. Ligozzi, H. Lopez, A. Sucari, a nd G. Satta, Antimicrob, Agents Chemother. 38:1980-1983, 1994), The pb p5 gene of the highly resistant strain E. faecium 9439 was cloned and sequenced, The deduced amino acid sequence showed 77 and 54% homologie s with the PBPs 5 of Enterococcus hirae and Enterococcus faecalis, res pectively, A gene fragment coding for the C-terminal part of PBP 5 con taining the penicillin-binding domain was also cloned from several E. faecium strains with different levels of ampicillin resistance, Sequen ce comparison revealed a few point mutations, some of which resulted i n amino acid substitutions between SDN and KTG motifs in PBPs 5 of hig hly resistant strains, One of these converted a polar residue (the T r esidue at position 562 or 574) of PBP 5 produced by susceptible and mo derately resistant strains into a nonpolar one (A or I), This alterati on could be responsible for the altered phenotype of PBP 5 in highly r esistant strains.