Abstract
Two strains of Enterobacter cloacae were isolated from a patient before (strain MHN1) and during (strain MHN2) treatment with moxalactam and gentamicin. Strain MHN1 exhibited inducible ampC cephalosporinase production. In contrast, strain MHN2 expressed the enzyme constitutively at a 3,000-fold higher level. With the Escherichia coli ampC gene as a hybridization probe it was shown that the genomic arrangement of the ampC region was the same in both strains. To gain more insight into regulatory phenomena, the ampC genes were cloned, and their expression was studied in E. coli K-12. The ampC gene from MHN1 behaved normally and conferred inducible beta-lactam resistance. A regulatory region of at least 800 base pairs involved in controlling repression-induction was located immediately upstream of ampC. Surprisingly, when present in E. coli the ampC gene from MHN2 no longer overproduced the cephalosporinase, and inducible expression was observed. This indicates that in MHN2 stable cephalosporinase overproduction is controlled by another factor which is not linked to the ampC gene.
MeSH Terms
Anti-Bacterial Agents/pharmacology
Cephalosporinase/biosynthesis,genetics
Cloning, Molecular
DNA Restriction Enzymes
DNA, Bacterial/analysis
Drug Resistance, Microbial
Enterobacter/drug effects,enzymology,genetics
Enterobacteriaceae/genetics
Enzyme Induction
Escherichia coli/genetics
Gene Expression Regulation
Genes, Bacterial
Humans
Mutation
Nucleic Acid Hybridization
Plasmids
beta-Lactamases/genetics
beta-Lactams
Chemicals
Anti-Bacterial Agents
DNA, Bacterial
beta-Lactams
DNA Restriction Enzymes
Cephalosporinase
beta-Lactamases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Nicolas M H
Honore N
Jarlier V
Philippon A
Cole S T
References (30)
30 references, click to expand
-
Inducible beta-lactamase in Enterobacter.
J Gen Microbiol. 1967 Nov;49(2):277-85
PMID: 5183475
-
Protein measurement with the Folin phenol reagent.
J Biol Chem. 1951 Nov;193(1):265-75
PMID: 14907713
-
The use of analytical isoelectric focusing for detection and identification of beta-lactamases.
J Gen Microbiol. 1975 May;88(1):169-78
PMID: 807678
-
Susceptibility of Enterobacter to cefamandole: evidence for a high mutation rate to resistance.
Antimicrob Agents Chemother. 1976 Jun;9(6):970-4
PMID: 938026
-
The beta-lactamases of gram-negative bacteria and their role in resistance to beta-lactam antibiotics.
J Antimicrob Chemother. 1976 Jun;2(2):115-57
PMID: 783110
-
Screening lambdagt recombinant clones by hybridization to single plaques in situ.
Science. 1977 Apr 8;196(4286):180-2
PMID: 322279
-
Escherichia coli K-12 mutants hyperproducing chromosomal beta-lactamase by gene repetitions.
J Bacteriol. 1977 Dec;132(3):912-22
PMID: 336612
-
Construction and characterization of amplifiable multicopy DNA cloning vehicles derived from the P15A cryptic miniplasmid.
J Bacteriol. 1978 Jun;134(3):1141-56
PMID: 149110
-
Isolation and characterization of DNA repetitions carrying the chromosomal beta-lactamase gene of Escherichia coli K-12.
Mol Gen Genet. 1979 Jun 7;173(2):115-25
PMID: 386030
-
Beta-lactam resistance in clinical isolates of Escherichia coli caused by elevated production of the ampC-mediated chromosomal beta-lactamase.
Antimicrob Agents Chemother. 1979 Oct;16(4):427-33
PMID: 391149
-
A bacteriophage lambda vector for cloning large DNA fragments made with several restriction enzymes.
Gene. 1980 Aug;10(3):249-59
PMID: 6254843
-
ampC cephalosporinase of Escherichia coli K-12 has a different evolutionary origin from that of beta-lactamases of the penicillinase type.
Proc Natl Acad Sci U S A. 1981 Aug;78(8):4897-901
PMID: 6795623
-
Cloning and expression in Escherichia coli K-12 of the genes for major outer membrane protein OmpA from Shigella dysenteriae, Enterobacter aerogenes, and Serratia marcescens.
J Bacteriol. 1982 Jan;149(1):145-50
PMID: 7033204
-
Nucleotide sequence coding for the flavoprotein subunit of the fumarate reductase of Escherichia coli.
Eur J Biochem. 1982 Mar 1;122(3):479-84
PMID: 7037404
-
Overlap between ampC and frd operons on the Escherichia coli chromosome.
Proc Natl Acad Sci U S A. 1982 Feb;79(4):1111-5
PMID: 7041115
-
Mutational enzymatic resistance of Enterobacter species to beta-lactam antibiotics.
Antimicrob Agents Chemother. 1982 Apr;21(4):655-60
PMID: 6979311
-
Trapping of nonhydrolyzable cephalosporins by cephalosporinases in Enterobacter cloacae and Pseudomonas aeruginosa as a possible resistance mechanism.
Antimicrob Agents Chemother. 1982 May;21(5):711-7
PMID: 6808912
-
Characterization of beta-lactamase induction in Enterobacter cloacae.
Antimicrob Agents Chemother. 1983 Jan;23(1):91-7
PMID: 6402977
-
Insertion of IS2 creates a novel ampC promoter in Escherichia coli.
Cell. 1983 Mar;32(3):809-16
PMID: 6187472
-
Broad-spectrum beta-lactam resistance in Enterobacter: emergence during treatment and mechanisms of resistance.
J Antimicrob Chemother. 1983 Apr;11(4):299-310
PMID: 6602122
-
Comparison of the overlapping frd and ampC operons of Escherichia coli with the corresponding DNA sequences in other gram-negative bacteria.
J Bacteriol. 1983 Sep;155(3):1297-305
PMID: 6350266
-
Emergence of resistance during therapy with the newer beta-lactam antibiotics: role of inducible beta-lactamases and implications for the future.
Rev Infect Dis. 1983 Jul-Aug;5(4):639-48
PMID: 6353526
-
Overlapping genes.
Annu Rev Genet. 1983;17:499-525
PMID: 6198955
-
Identification of a novel ampC beta-lactamase promoter in a clinical isolate of Escherichia coli.
EMBO J. 1982;1(11):1411-6
PMID: 6765197
-
[Enterobacter cloacae. In vivo emergence of a variant resistant to new beta-lactams during treatment with lamoxactam-gentamicin].
Pathol Biol (Paris). 1984 May;32(5):399-403
PMID: 6739148
-
Epidemiology of enterobacteria resistant to cefotaxime in hospital.
J Antimicrob Chemother. 1984 Sep;14 Suppl B:53-7
PMID: 6094463
-
Survey of the phenotypes of susceptibility to beta-lactams in Enterobacteriaceae at the Pitie-Salpetriere Hospital.
J Antimicrob Chemother. 1984 Sep;14 Suppl B:59-65
PMID: 6501135
-
Regulatory components in Citrobacter freundii ampC beta-lactamase induction.
Proc Natl Acad Sci U S A. 1985 Jul;82(14):4620-4
PMID: 2991883
-
Gram-negative bacilli resistant to third-generation cephalosporins: beta-lactamase characterization and susceptibility to Sch 34343.
J Antimicrob Chemother. 1985 Jun;15 Suppl C:119-32
PMID: 3875602
-
Computerized microacidimetric determination of beta lactamase Michaelis-Menten constants.
FEBS Lett. 1973 Jun 15;33(1):42-4
PMID: 4198636