M. Ligozzi et al., MODIFICATION OF PENICILLIN-BINDING PROTEIN-5 ASSOCIATED WITH HIGH-LEVEL AMPICILLIN RESISTANCE IN ENTEROCOCCUS-FAECIUM, Antimicrobial agents and chemotherapy, 40(2), 1996, pp. 354-357
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.