Open AccessImpact of Specific pbp5 Mutations on Expression of β-Lactam Resistance in Enterococcus faecium
Author(s) -
Louis B. Rice,
Samuel Bellais,
Lenore L. Carias,
Rebecca Hutton-Thomas,
Robert A. Bonomo,
Patrick Caspers,
Malcolm G. P. Page,
Laurent Gutmann
Publication year - 2004
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.48.8.3028-3032.2004
Subject(s) - enterococcus faecium , biology , amp resistance , genetics , plasmid , point mutation , penicillin binding proteins , enterococcus , mutant , ampicillin , mutation , serine , penicillin , microbiology and biotechnology , gene , antibiotics , phosphorylation
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 beta-lactams. Affinity for penicillin generally correlated with beta-lactam MICs for the mutants, but these associations were not strictly proportional.