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Antimicrobial Agents and Chemotherapy, August 2004, p. 3028-3032, Vol. 48, No. 8
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.8.3028-3032.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Impact of Specific pbp5 Mutations on Expression of ß-Lactam Resistance in Enterococcus faecium

Medical and Research Services, Louis Stokes Cleveland VA Medical Center,¹ Case Western Reserve University, Cleveland, Ohio,² LRMA, INSERM E0004, Université Paris VI, 75270 Paris Cedex 06, France,³ Basilea Pharmaceutica, CH-4005 Basel, Switzerland⁴

Received 28 January 2004/ Returned for modification 14 March 2004/ Accepted 8 April 2004

We tested the impact of individual PBP 5 mutations on expression of ampicillin resistance in Enterococcus faecium using a shuttle plasmid designed to facilitate expression of cloned pbp5 in ampicillin-susceptible E. faecium D344SRF. Substitutions that had been implicated in contributing to the resistance of clinical strains conferred only modest levels of resistance when they were present as single point mutations. The levels of resistance were amplified when some mutations were present in combination. In particular, a methionine-to-alanine change at position 485 (in close proximity to the active site) combined with the insertion of a serine at position 466 (located in a loop that forms the outer edge of the active site) was associated with the highest levels of resistance to all ß-lactams. Affinity for penicillin generally correlated with ß-lactam MICs for the mutants, but these associations were not strictly proportional.

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