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PMID: 8052644 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Analysis of a carbapenem-hydrolyzing class A beta-lactamase from Enterobacter cloacae and of its LysR-type regulatory protein.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 16 ·1994-08-02 ·Pages 7693-7

Naas T, Nordmann P

Abstract

Carbapenems such as imipenem are extended-spectrum beta-lactam antibiotics, which are not hydrolyzed by the beta-lactamases commonly found in Enterobacteriaceae. Here we report a gene encoding a carbapenemase, which was cloned from the chromosome of a clinical isolate of Enterobacter cloacae, strain NOR-1, into pACYC184 plasmid in Escherichia coli. Unlike all the sequenced carbapenemases, which are class B metallo-beta-lactamases, the mature protein (NmcA) is a class A serine beta-lactamase. NmcA shares the highest amino acid identity (50%) with the extended-spectrum class A beta-lactamase MEN-1 from E. coli. In the opposite orientation from the nmcA promoter, an overlapping and divergent promoter was detected, along with an open reading frame, which encoded a 33.5-kDa protein (NmcR). The NmcR amino acid sequence displays homology with LysR-type transcriptional regulatory proteins, including the conserved residues near its N terminus within a helix-turn-helix motif. Deletion of nmcR resulted in decreased carbapenem resistance and a loss of beta-lactamase inducibility, demonstrating a positive role of NmcR in NmcA expression.

Related Genes
lysR nmcA nmcR
MeSH Terms
Amino Acid Sequence Bacterial Proteins/genetics Base Sequence Carbapenems/metabolism DNA Mutational Analysis Drug Resistance, Microbial/genetics Enterobacter cloacae/enzymology,genetics Gene Expression Regulation Gene Expression Regulation, Bacterial Gene Expression Regulation, Enzymologic Hydrolysis Molecular Sequence Data Restriction Mapping Sequence Analysis Sequence Deletion Sequence Homology, Amino Acid Transcription Factors/genetics Transcription, Genetic beta-Lactamases/genetics
Chemicals
Bacterial Proteins Carbapenems Transcription Factors LysR protein, Bacteria NmcA protein, Enterobacter cloacae beta-Lactamases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Naas T
Abteilung Mikrobiologie, Biozentrum der Universität Basel, Switzerland.
Nordmann P
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26 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.91.16.7693
Published
1994-08-02
Pages
7693-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC44468
Subset
IM
Databases
GENBANK
Z21956
External Links
PubMed source DOI: 10.1073/pnas.91.16.7693 PMC Full Text View journal details
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