NDLI: Carbapenem Resistance in Escherichia coli Associated with Plasmid-Determined CMY-4 β-Lactamase Production and Loss of an Outer Membrane Protein

Content Provider	PubMed Central
Author	Stapleton, Paul D. Shannon, Kevin P. French, Gary L.
Copyright Year	1999
Abstract	Three cefoxitin-resistant Escherichia coli isolates from stool specimens of a patient with leukemia were either resistant, intermediate, or sensitive to imipenem. Conjugation experiments showed that cefoxitin resistance, but not imipenem resistance, was transferable. All isolates were shown by isoelectric focusing to produce two β-lactamases with isoelectric points of 5.4 (TEM-1, confirmed by sequencing of a PCR product) and >8.5 (consistent with a class C β-lactamase). The gene coding for the unknown β-lactamase was cloned and sequenced and revealed an enzyme which had 99.9% sequence identity with the plasmid-determined class C β-lactamase CMY-2. The cloned β-lactamase gene differed from bla CMY-2 at one nucleotide position that resulted in an amino acid change, tryptophan to arginine at position 221. We propose that this enzyme be designated CMY-4. Both the imipenem-resistant and -intermediate isolates lacked a 38-kDa outer membrane protein (OMP) that was present in the imipenem-sensitive isolate. The lack of an OMP alone did not explain the difference in carbapenem susceptibilities observed. However, measurement of β-lactamase activities (including measurements under conditions where TEM-1 β-lactamase was inhibited) indicated that the imipenem-intermediate isolate expressed six- to eightfold less β-lactamase than did the other isolates. This study illustrates that carbapenem resistance in E. coli can arise from high-level expression of plasmid-mediated class C β-lactamase combined with an OMP deficiency. Furthermore, in the presence of an OMP deficiency, the level of expression of a plasmid-mediated class C β-lactamase is an important factor in determining whether E. coli isolates are fully resistant to carbapenems.
Starting Page	1206
File Format	PDF
ISSN	10986596
e-ISSN	10986596
Journal	Antimicrobial Agents and Chemotherapy
Issue Number	5
Volume Number	43
Language	English
Publisher	American Society for Microbiology
Publisher Date	1999-05-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Pharmacology Pharmacology (medical)

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