Abstract
The sequences of the promoter regions and of the structural genes for 13 penicillinase, extended-spectrum, and inhibitor-resistant TEM-type β-lactamases have been determined, and an updated blaTEM gene nomenclature is proposed.
In members of the family Enterobacteriaceae, the most prevalent mechanism of resistance to broad-spectrum β-lactams is detoxification of the drugs by plasmid-mediated enzymes that are variants of TEM and SHV penicillinases (4, 13). The TEM-derived extended-spectrum or inhibitor-resistant β-lactamases differ from the parental TEM-1 and TEM-2 penicillinases by various combinations of amino acid substitutions. The structural genes for TEM-1 penicillinases are designated blaTEM-1a and blaTEM-1b, and the structural gene for TEM-2 is designated blaTEM-2 (10). As an aid to the study of the mutational events which account for the sequence diversity of TEM-type β-lactamases and to the nomenclature of the numerous variants, we have determined and analyzed the sequences of the structural genes and of the promoters of various blaTEM genes. Amplification and direct sequencing of the PCR product were as described previously (15). The origins (Table 1) and the nucleotide changes in the blaTEM genes and the corresponding amino acid substitutions in the deduced sequence of the enzymes (Tables 2 and 3) are summarized.
TABLE 1.
Origins of the enzymes studied
| Enzyme | Alternate designation(s) | Gene(s) | Clinical isolate(s) | Origin or reference |
|---|---|---|---|---|
| TEM-1 | blaTEM-1c | E. coli BM2729 | This work | |
| TEM-8 | CAZ-2 | blaTEM-8 | K. pneumoniae HM12 | 14, 17 |
| TEM-10 | TEM-23, MGH-1 | blaTEM-10b and blaTEM-23 | E. coli F2 | 26 |
| TEM-11 | CAZ-lo | blaTEM-11 | E. coli 1724A | 14, 27 |
| TEM-12 | TEM-101, YOU-2, CAZ-3 | blaTEM-12c | E. coli F1, E. coli MG32 | 26, 28 |
| TEM-13 | blaTEM-13 | M. morganii BM2717 | 14 | |
| TEM-15 | blaTEM-15a | K. pneumoniae BM2730 | 14 | |
| TEM-15 | TEM-17 | blaTEM-15b | K. pneumoniae BM2731 and BM2732 | 14 |
| TEM-24 | CAZ-6 | blaTEM-24b | E. aerogenes SLE48 | This work |
| TEM-53 | blaTEM-53 | K. pneumoniae BM2733 | This work | |
| TEM-33 | IRT-5 | blaTEM-33b | E. coli BM2725 | This work |
| TEM-33 | IRT-5 | blaTEM-33c | E. coli BM2724 | This work |
| TEM-54 | blaTEM-54 | E. coli BM2728 | This work |
TABLE 2.
Substitutions in blaTEM genes and derived penicillinases and extended-spectrum β-lactamases
| Region and nucleotide no.a (amino acid no.b) | Nucleotide (amino acid) in the following gene (enzyme):
|
|||||
|---|---|---|---|---|---|---|
| blaTEM-1a (TEM-1 [Tn3]) | blaTEM-1b (TEM-1 [Tn2]) | blaTEM-2 (TEM-2 [Tn1]) | blaTEM-1c (TEM-1) | blaTEM-8 (TEM-8) | blaTEM-10b (TEM-10) | |
| Promoter region | P3 | P3 | Pa and Pb | P3 | Pa and Pb | Pa and Pb |
| 32 | C | C | T | C | T | T |
| 147 | T | T | T | T | A | T |
| 162 | G | G | G | G | G | G |
| 175 | A | G | A | A | A | G |
| Coding region | ||||||
| 226d | C (Phe) | T | C | C | C | T |
| 263 (21) | C (Leu)21 | C | C | C | C | C |
| 317 (39) | C (Gln)39 | C (Gln)39 | A (Lys)39 | C (Gln)39 | A (Lys)39 | C (Gln)39 |
| 346d | A (Glu) | A | G | A | G | A |
| 436d | C (Gly) | T | T | T | T | T |
| 512 (104) | G (Glu)104 | G | G | G | A (Lys)104 | G |
| 604d | G (Ala) | T | G | G | G | T |
| 682d | T (Thr) | T | C | T | C | T |
| 692 (164) | C (Arg)164 | C | C | C | A (Ser)164 | A (Ser)164 |
| 693 (164) | G (Arg)164 | G | G | G | G | G |
| 911 (237) | G (Ala)237 | G | G | G | G | G |
| 914 (238) | G (Gly)238 | G | G | G | A (Ser)238 | G |
| 917 (240) | G (Glu)240 | G | G | G | G | A (Lys)240 |
| 925d | G (Gly) | G | A | G | A | G |
| 990 (265) | C (Thr)265 | C | C | C | C | C |
| Nucleotide (amino acid) in the following gene (enzyme):
| ||||||
|---|---|---|---|---|---|---|
| blaTEM-11 (TEM-11) | blaTEM-12c (TEM-12) | blaTEM-13 (TEM-13) | blaTEM-15a (TEM-15) | blaTEM-15b (TEM-15) | blaTEM-24b (TEM-24) | blaTEM-53 (TEM-53) |
| Pa and Pb | Pa and Pb or P3 | P3 | P4 | Pa and Pb | Pa and Pb | Pa and Pb |
| T | T/Cc | C | C | T | T | T |
| T | T | T | T | T | A | T |
| G | G | G | T | G | G | G |
| A | G | A | A | G | A | A |
| C | T | C | C | T | C | C |
| C | C | C | C | C | C | T (Phe)21 |
| A (Lys)39 | C (Gln)39 | A (Lys)39 | C (Gln)39 | C (Gln)39 | A (Lys)39 | C (Gln)39 |
| G | A | G | A | A | G | G |
| T | T | T | C | T | T | T |
| G | G | G | A (Lys)104 | A (Lys)104 | A (Lys)104 | G |
| G | T | G | G | T | G | G |
| C | T | C | T | T | C | C |
| C | A (Ser)164 | C | C | C | A (Ser)164 | A (Ser)164 |
| A (His)164 | G | G | G | G | G | G |
| G | G | G | G | G | A (Thr)237 | G |
| G | G | G | A (Ser)238 | A (Ser)238 | G | G |
| G | G | G | G | G | A (Lys)240 | G |
| G | G | A | G | G | G | A |
| C | C | T (Met)265 | C | C | C | C |
TABLE 3.
Substitutions in blaTEM genes and derived inhibitor-resistant β-lactamases
| Region and nucleotide no.a (amino acid no.b) | Nucleotide (amino acid) in the following gene (enzyme):
|
|||||
|---|---|---|---|---|---|---|
| blaTEM-1a (TEM-1 [Tn3]) | blaTEM-1b (TEM-1 [Tn2]) | blaTEM-2 (TEM-2 [Tn1]) | blaTEM-33b (TEM-33) | blaTEM-33c (TEM-33) | blaTEM-54 (TEM-54) | |
| Promoter region | P3 | P3 | Pa and Pb | Pa and Pb | P4 | Pa and Pb |
| 32 | C | C | T | T | C | T |
| 162 | G | G | G | G | T | G |
| 175 | A | G | A | G | A | A |
| Coding region | ||||||
| 226c | C (Phe) | T | C | T | C | C |
| 317 (39) | C (Gln)39 | C (Gln)39 | A (Lys)39 | C (Gln)39 | C (Gln)39 | C (Gln)39 |
| 346c | A (Glu) | A | G | A | G | A |
| 407 (69) | A (Met)69 | A | A | C (Leu)69 | C (Leu)69 | A |
| 436c | C (Gly) | T | T | T | T | C |
| 604c | G (Ala) | T | G | T | G | G |
| 682c | T (Thr) | T | C | T | C | T |
| 925c | G (Gly) | G | A | G | A | G |
| 929 (244) | C (Arg)244 | C | C | C | C | C |
| 930 (244) | G (Arg)244 | G | G | G | G | T (Leu)244 |
| 1022 (276) | A (Asn)276 | A | A | A | A | A |
Two promoters for initiation of transcription of the blaTEM genes have been described: the weak P3 promoter for blaTEM-1 in Tn3 (20) and, following a C-to-T substitution at position 32, the two overlapping promoters (Pa and Pb) which lead to a ca. 10-fold increase in transcriptional levels (8).
Penicillinases. (i) blaTEM-1c.
Escherichia coli BM2729 was isolated in 1989 and has a phenotype of resistance to β-lactam antibiotics which corresponds to the synthesis of a penicillinase. The corresponding blaTEM-1c gene differs from blaTEM-1a by the nucleotide substitution C436→T, which is silent.
(ii) blaTEM-13.
Morganella morganii BM2717 (14) harbored a plasmid that carries both the blaTEM-2 and the blaTEM-13 genes (data not shown). The sequence of blaTEM-13 differs from that of blaTEM-2 by C990→T, resulting in Thr265→Met, as determined by oligotyping (14). Most interestingly, upstream from blaTEM-13 and blaTEM-2 we found the weak promoter P3 (C32) instead of the expected strong promoters Pa and Pb. The presence of the two genes on the same replicon could therefore result from gene duplication followed by a point mutation.
Extended-spectrum β-lactamases. (i) blaTEM-8.
The TEM-8 extended-spectrum β-lactamase, later designated CAZ-2 (6), was detected in Klebsiella pneumoniae HM12, which was isolated in 1987, and the structural gene for the enzyme was sequenced (6, 17). The promoter region has a thymine at position 32 (Table 2) which was not reported for the gene for CAZ-2. The blaTEM-8 gene derives from blaTEM-2 by three base pair changes and differs from blaTEM-3 at position 692, where a C-to-A substitution leads to Arg164→Ser.
(ii) blaTEM-11.
The gene for the extended-spectrum β-lactamase TEM-11 harbored by E. coli 1724A (27) was oligotyped (14), with a remaining ambiguity found at position 238, and was characterized by restriction fragment length polymorphism analysis, which revealed an adenine at position 925 (2). However, sequence determination indicated G925 (Table 2). Thus, the blaTEM-11 gene differs from blaTEM-2 at two positions, G693→A, resulting in Arg164→His, and A925→G, which is silent. The strong promoters Pa and Pb for that gene are identical to those for blaTEM-2. The blaTEM-11 gene could therefore result from a recombination event, in the vicinity of position 692, between blaTEM-2, which would have provided the 5′ portion of the gene, and blaTEM-6 (11), which would have contributed the 3′ part of the gene. Alternatively, the blaTEM-11 gene could be a point mutant from a yet uncharacterized TEM-2 progenitor with a G925 or a double mutant of blaTEM-2.
(iii) blaTEM-15a.
The gene for extended-spectrum β-lactamase TEM-15 from K. pneumoniae BM2730 was oligotyped (14) and was sequenced without the promoter (21). We have resequenced the entire region whose sequence differs from that of blaTEM-1a at three positions: G512→A (Glu104→Lys), G914→A (Gly238→Ser), and G162→T. The last change occurs at position 1 of the −10 consensus Pribnow box sequence of the P3 promoter and has been shown to be responsible for the hyperproduction of TEM-1 (22). We suggest the designation P4 for this new promoter. Since this structural gene was apparently derived from blaTEM-1a, we propose the nomenclature blaTEM-15a.
(iv) blaTEM-15b.
The deduced amino acid sequence of blaTEM-15b is identical to that of blaTEM-15a. The enzyme, formerly designated TEM-17 on the basis of oligotyping (14), was therefore redesignated TEM-15. The TEM-17 sequence that we originally proposed has subsequently been found in Capnocytophaga ochracea (EMBL accession no. Y14574). The sequence of blaTEM-15b differs from that of blaTEM-1b at two positions: G512→A, which leads to Glu104→Lys, and G914→A, which results in Gly238→Ser, whereas the strong Pa and Pb promoters are present upstream. We thus suggest the designation blaTEM-15b since this gene is likely to be derived from blaTEM-1b. The TEM-15 β-lactamase displays the same amino acid substitutions which enlarge the substrate range of TEM-3, except that TEM-15 has Gln39 instead of Lys.
(v) blaTEM-12c and blaTEM-10b.
blaTEM-12c and blaTEM-10b originate from two E. coli strains, F1 and F2, which were isolated from the same patient at a 24-h interval (26). The blaTEM-12c gene is identical to blaTEM-12, which encodes YOU-2 (19), and is located downstream from the Pa and Pb promoters. Since blaTEM-12a refers to the structural gene for TEM-101 (9) and blaTEM-12b is the designation for the gene described by Heritage et al. (12) and also the gene for CAZ-3 (7), we propose the nomenclature blaTEM-12c. We also found a blaTEM-12c gene in E. coli MG32 (28). This gene was chromosomally located and, in an unusual fashion, was preceded by the weak P3 promoter.
The sequence of blaTEM-10b differs from that of blaTEM-12c by a single base pair change, G917→A, which results in Glu240→Lys. The blaTEM-10b gene is identical to blaTEM-10 from plasmids pJPQ100 and pMG223 in K. pneumoniae and pCLL2302 in E. coli (18, 19). These genes could be designated blaTEM-10b since they are derived from blaTEM-1b; blaTEM-10a would then correspond to the gene carried by pCLL2301 from K. pneumoniae (18), which is derived from blaTEM-1a. The structural genes for TEM-10 and TEM-12 have previously been detected in the same clinical isolate (3).
(vi) blaTEM-24b.
The sequence of blaTEM-24 encoding TEM-24 (or CAZ-6) has been published with only part of the promoter region (6), and we suggest the designation blaTEM-24a. The sequence of blaTEM-24b differs by a silent mutation (T682→C) from that of blaTEM-24a and is under the control of the strong promoters Pa and Pb. It has been proposed that blaTEM-24a could result from recombination of blaTEM-3 and blaTEM-5 between positions 604 and 682 (6). Similarly, blaTEM-24b could originate from a recombination event between positions 693 and 911 of blaTEM-8 (6, 17) and blaTEM-5 (23). Whatever the authentic origin of the gene may be, our observation documents dissemination of TEM-24 in Enterobacter aerogenes.
(vii) blaTEM-53.
The sequence of the new mutant gene blaTEM-53 differs from that of blaTEM-2 at three loci, with each base pair change leading to an amino acid substitution: C263→T (Leu21→Phe), A317→C (Lys39→Gln), and C692→A (Arg164→Ser). The gene is expressed from the strong promoters Pa and Pb. It is worth noting that the corresponding mature protein is identical to TEM-12. This gene could be secondary to a recombination event, between positions 436 and 512, of blaTEM-4 (23) or blaTEM-9 (16), which would provide the 5′ third of the gene, and blaTEM-7 (9), which would correspond to the 3′ two-thirds.
Inhibitor-resistant β-lactamases. (i) blaTEM-33.
The sequence of blaTEM-33, which we propose be renamed blaTEM-33a, has been published (24). We report here the sequence of two genes, designated blaTEM-33b and blaTEM-33c, that have been detected in clinical isolates (Table 1).
(ii) blaTEM-33b.
The structural gene has the mutation A407→C relative to the sequence of blaTEM-1b, resulting in Met69→Leu, and is under the control of the Pa and Pb promoters.
(iii) blaTEM-33c.
blaTEM-33c is derived from blaTEM-2 following two changes: A317→C (Lys39→Gln) and A407→C (Met69→Leu). The promoter region has the G162→T mutation, which is commonly found upstream from the genes for inhibitor-resistant β-lactamases. Thus, the blaTEM-33c gene is derived from that for the “TEM-2 like” enzyme (5), which consists of TEM-2 with Lys39→Gln and the T32→C and G162→T mutations upstream from the gene.
(iv) blaTEM-54.
blaTEM-54 has not yet been described and originates from E. coli BM2728 (Table 1). It derives from blaTEM-1a following one mutation, G930→T, which leads to the amino acid change Arg244→Leu, whereas the promoter region corresponds to Pa and Pb.
In summary, we have determined the sequences of the structural genes and of the promoter regions specifying two TEM-derived penicillinases, eight extended-spectrum β-lactamases, and three inhibitor-resistant β-lactamases. The sequence variety found probably reflects the existence in nature of genes other than blaTEM-1a, blaTEM-1b, blaTEM-1c, blaTEM-2, and blaTEM-13 for penicillinases. With the exception of chromosomal blaTEM-12, the genes were located downstream from strong promoters such as Pa and Pb and the new promoter P4.
Nucleotide sequence accession numbers.
The nucleotide sequence data for blaTEM-53 and blaTEM-54 have been submitted to the GenBank nucleotide sequence data library under accession no. AF104441 and AF104442, respectively.
Acknowledgments
We thank G. Arlet, G. Aubert, R. Bismuth, V. Jarlier, T. Lambert, P. Legrand, D. Lesage, G. Vedel, G. Verschraegen, and D. A. Weber for gifts of strains.
This work was supported in part by a Bristol-Myers Squibb Unrestricted Biomedical Research Grant in Infectious Diseases.
REFERENCES
- 1.Ambler R P, Coulson A F, Frere J M, Ghuysen J M, Joris B, Forsman M, Levesque R C, Tiraby G, Waley S G. A standard numbering scheme for the class A β-lactamases. Biochem J. 1991;276:269–270. doi: 10.1042/bj2760269. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Arlet G, Brami G, Decré D, Flippo A, Gaillot O, Lagrange P H, Philippon A. Molecular characterization by PCR-restriction fragment length polymorphism of TEM β-lactamases. FEMS Microbiol Lett. 1995;134:203–208. doi: 10.1111/j.1574-6968.1995.tb07938.x. [DOI] [PubMed] [Google Scholar]
- 3.Bradford P A, Cherubin C E, Idemyor V, Rasmussen B A, Bush K. Multiply resistant Klebsiella pneumoniae strains from two Chicago hospitals: identification of the extended-spectrum TEM-12 and TEM-10 ceftazidime-hydrolyzing β-lactamases in a single isolate. Antimicrob Agents Chemother. 1994;38:761–766. doi: 10.1128/aac.38.4.761. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Bush K, Jacoby G. Nomenclature of TEM β-lactamases. J Antimicrob Chemother. 1997;39:1–3. doi: 10.1093/jac/39.1.1. [DOI] [PubMed] [Google Scholar]
- 5.Caniça M M, Lu C Y, Krishnamoorthy R, Paul G C. Molecular diversity and evolution of blaTEM genes encoding β-lactamases resistant to clavulanic acid in clinical E. coli. J Mol Evol. 1997;44:57–65. doi: 10.1007/pl00006121. [DOI] [PubMed] [Google Scholar]
- 6.Chanal C, Poupart M-C, Sirot D, Labia R, Sirot J, Cluzel R. Nucleotide sequences of CAZ-2, CAZ-6, and CAZ-7 β-lactamase genes. Antimicrob Agents Chemother. 1992;36:1817–1820. doi: 10.1128/aac.36.9.1817. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Chanal C, Sirot D, Malaure H, Poupart M-C, Sirot J. Sequences of CAZ-3 and CTX-2 extended-spectrum β-lactamase genes. Antimicrob Agents Chemother. 1994;38:2452–2453. doi: 10.1128/aac.38.10.2452. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Chen S-T, Clowes R C. Two improved promoter sequences for the β-lactamase expression arising from a single base-pair substitution. Nucleic Acids Res. 1984;12:3219–3234. doi: 10.1093/nar/12.7.3219. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Collatz E, Tran Van Nhieu G, Billot-Klein D, Williamson R, Gutmann L. Substitution of serine for arginine in position 162 of TEM-type β-lactamases extends the substrate profile of mutant enzymes, TEM-7 and TEM-101, to ceftazidime and aztreonam. Gene. 1989;78:349–354. doi: 10.1016/0378-1119(89)90237-0. [DOI] [PubMed] [Google Scholar]
- 10.Goussard S, Courvalin P. Sequence of the genes blaT-1B and blaT-2. Gene. 1991;102:71–73. doi: 10.1016/0378-1119(91)90540-r. [DOI] [PubMed] [Google Scholar]
- 11.Goussard S, Sougakoff W, Mabilat C, Bauernfeind A, Courvalin P. An IS1-like element is responsible for high-level synthesis of extended-spectrum β-lactamase TEM-6 in Enterobacteriaceae. J Gen Microbiol. 1991;137:2681–2687. doi: 10.1099/00221287-137-12-2681. [DOI] [PubMed] [Google Scholar]
- 12.Heritage J, Hawkey P M, Todd N, Lewis I J. Transposition of the gene encoding a TEM-12 extended-spectrum β-lactamase. Antimicrob Agents Chemother. 1992;36:1981–1986. doi: 10.1128/aac.36.9.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Jacoby, G., and K. Bush. Amino acid sequences for TEM, SHV, and OXA extended-spectrum and inhibitor resistant β-lactamases. http://www.lahey.org/studies/webt.htm.
- 14.Mabilat C, Courvalin P. Development of “oligotyping” for characterization and molecular epidemiology of TEM β-lactamases in members of the family Enterobacteriaceae. Antimicrob Agents Chemother. 1990;34:2210–2216. doi: 10.1128/aac.34.11.2210. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Mabilat C, Goussard S. PCR detection and identification of genes for extended-spectrum β-lactamases. In: Persing D H, Smith T F, Tenover F C, White T J, editors. Diagnostic molecular microbiology: principles and applications. Washington, D.C: American Society for Microbiology; 1993. pp. 553–559. [Google Scholar]
- 16.Mabilat C, Goussard S, Sougakoff W, Spencer R C, Courvalin P. Direct sequencing of the amplified structural gene and promoter for the extended-broad-spectrum β-lactamase TEM-9 (RHH-1) of Klebsiella pneumoniae. Plasmid. 1990;23:27–34. doi: 10.1016/0147-619x(90)90041-a. [DOI] [PubMed] [Google Scholar]
- 17.Mabilat C, Legrand P, Duval J, Courvalin P. Analyse de la séquence nucléotidique du gène blaT-8 codant la β-lactamase à spectre élargi TEM-8, abstr. 136/P12. Paris, France: Réunion Interdisciplinaire de Chimiothérapie Antiinfectieuse; 1989. [Google Scholar]
- 18.Rasmussen B A, Bradford P A, Quinn J P, Wiener J, Weinstein R A, Bush K. Genetically diverse ceftazidime-resistant isolates from a single center: biochemical and genetic characterization of TEM-10 β-lactamases encoded by different nucleotide sequences. Antimicrob Agents Chemother. 1993;37:1989–1992. doi: 10.1128/aac.37.9.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Rice L B, Marshall S H, Carias L L, Sutton L, Jacoby G A. Sequences of MGH-1, YOU-1, and YOU-2 extended-spectrum β-lactamase genes. Antimicrob Agents Chemother. 1993;37:2760–2761. doi: 10.1128/aac.37.12.2760. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Russell D R, Bennett G N. Characterization of the β-lactamase promoter of pBR322. Nucleic Acids Res. 1981;11:2517–2532. doi: 10.1093/nar/9.11.2517. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Sirot D, Recule C, Chaibi E B, Bret L, Croize J, Chanal-Claris C, Labia R, Sirot J. A complex mutant of TEM-1 β-lactamase with mutations encountered in both IRT-4 and extended-spectrum TEM-15, produced by an Escherichia coli clinical isolate. Antimicrob Agents Chemother. 1997;41:1322–1325. doi: 10.1128/aac.41.6.1322. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Siu L K, Ho P L, Yuen K Y, Wong S S Y, Chau P Y. Transferable hyperproduction of TEM-1 β-lactamase in Shigella flexneri due to a point mutation in the Pribnow box. Antimicrob Agents Chemother. 1997;41:468–470. doi: 10.1128/aac.41.2.468. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Sougakoff W, Petit A, Goussard S, Sirot D, Buré A, Courvalin P. Characterization of the plasmid genes blaT-4 and blaT-5 which encode the broad spectrum β-lactamases TEM-4 and TEM-5 in Enterobacteriaceae. Gene. 1989;78:339–348. doi: 10.1016/0378-1119(89)90236-9. [DOI] [PubMed] [Google Scholar]
- 24.Speldooren V, Heym B, Labia R, Nicolas-Chanoine M-H. Discriminatory detection of inhibitor-resistant β-lactamases in Escherichia coli by single-strand conformation polymorphism-PCR. Antimicrob Agents Chemother. 1998;42:879–884. doi: 10.1128/aac.42.4.879. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Sutcliffe G. Nucleotide sequence of the ampicillin resistance gene of Escherichia coli plasmid pBR322. Proc Natl Acad Sci USA. 1978;75:3737–3741. doi: 10.1073/pnas.75.8.3737. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Vedel G, Mabilat C, Goussard S, Picard B, Fournier G, Gilly L, Paul G, Philippon A. Two variants of transferable extended-spectrum TEM-β-lactamase successively isolated from a clinical Escherichia coli isolate. FEMS Microbiol Lett. 1992;93:161–166. doi: 10.1016/0378-1097(92)90522-p. [DOI] [PubMed] [Google Scholar]
- 27.Vuye A, Verschraegen G, Claeys G. Plasmid-mediated β-lactamases in clinical isolates of Klebsiella pneumoniae and Escherichia coli resistant to ceftazidime. Antimicrob Agents Chemother. 1989;33:757–761. doi: 10.1128/aac.33.5.757. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Weber D A, Sanders C C, Bakken J S, Quinn J P. A novel chromosomal TEM derivative and alterations in outer membrane proteins together mediate selective ceftazidime resistance in Escherichia coli. J Infect Dis. 1990;162:460–465. doi: 10.1093/infdis/162.2.460. [DOI] [PubMed] [Google Scholar]