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Mechanisms of Resistance

TEM-184, a Novel TEM-Derived Extended-Spectrum β-Lactamase with Enhanced Activity against Aztreonam

Alessandra Piccirilli, Mariagrazia Perilli, Gianfranco Amicosante, Viola Conte, Carlo Tascini, Gian Maria Rossolini, Tommaso Giani
Alessandra Piccirilli
aDipartimento di Scienze Cliniche Applicate e Biotecnologiche, Università degli Studi dell'Aquila, L'Aquila, Italy
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Mariagrazia Perilli
aDipartimento di Scienze Cliniche Applicate e Biotecnologiche, Università degli Studi dell'Aquila, L'Aquila, Italy
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Gianfranco Amicosante
aDipartimento di Scienze Cliniche Applicate e Biotecnologiche, Università degli Studi dell'Aquila, L'Aquila, Italy
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Viola Conte
bDipartimento di Biotecnologie Mediche, Università degli Studi di Siena, Siena, Italy
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Carlo Tascini
cDepartment of Infectious Diseases, Cotugno Hospital, Naples, Italy
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Gian Maria Rossolini
dDipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Florence, Italy
eSOD Microbiologia e Virologia, Azienda Ospedaliera Universitaria Careggi, Florence, Italy
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Tommaso Giani
dDipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Florence, Italy
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DOI: 10.1128/AAC.00688-18
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ABSTRACT

TEM-184, a novel TEM-derived extended-spectrum β-lactamase (ESBL), was isolated from an Escherichia coli ST354 clinical strain. Compared to TEM-1, TEM-184 contains the mutations Q6K, E104K, I127V, R164S, and M182T. Kinetic analysis of this enzyme revealed extended-spectrum activity against aztreonam in particular. TEM-184 was also susceptible to inhibitors, including clavulanic acid, tazobactam, and avibactam.

TEXT

TEM-type enzymes are likely the most prevalent acquired β-lactamases among Escherichia coli and other Enterobacterales in the clinical setting and were the first broad-spectrum enzymes showing the ability to evolve extended-spectrum β-lactamase (ESBL) activity or resistance to mechanism-based inhibitors following specific amino acid replacements (1, 2). Indeed, a very large array of TEM variants with ESBL activity and a lower number of variants resistant to inhibitors (IRT) or with a combined phenotype (CMT) have been described (ftp://ftp.ncbi.nlm.nih.gov/pathogen/betalactamases/allele.tab), underscoring the outstanding evolutionary plasticity of these enzymes, and characterization of these variants has provided an invaluable amount of information on the structure-function relationships of these enzymes and, more generally, of serine β-lactamases.

In this study, we identified and characterized, from a kinetic point of view, a novel natural TEM-type variant with ESBL activity, named TEM-184, isolated from an E. coli clinical isolate.

The blaTEM-184 gene was detected in E. coli isolated from abdominal drainage of an elderly patient who had undergone abdominal surgery for a relapsing colonic adenocarcinoma. The patient had received amoxicillin-clavulanate for 24 h as surgical prophylaxis. After 5 days, the patient developed a surgical-site infection, yielding an E. coli isolate resistant to fluoroquinolones and cefotaxime but susceptible to ceftazidime, aztreonam, and carbapenems (isolate CT-Eco1, not stored), and was treated with ceftazidime (2 g t.i.d.). After initial improvement, fever and signs of infection relapsed, and an E. coli isolate that was also resistant to ceftazidime and aztreonam (isolate CT-Eco2) was isolated from the drainage discharge (Table 1). CT-Eco2 was positive for ESBL production by combo-disk test with cefotaxime and clavulanate (3). Genotyping by multilocus sequence typing (MLST) analysis using the Warwick schema (http://mlst.warwick.ac.uk) showed that the isolate belonged to sequence type 354 (ST354), a lineage that has been sporadically reported as responsible for invasive human infections and in association with β-lactamase production (NDM-5 and CMY-2 enzymes) (4, 5). Analysis of β-lactamase genes by PCR and sequencing revealed that CT-Eco2 carried a blaCTX-M-14 gene and a blaTEM gene that encoded a new TEM variant, i.e., TEM-184 (6). Compared with TEM-1, TEM-184 carried five amino acid modifications, including Q6K, E104K, I127V, R164S, and M182T, which were previously detected in other TEM variants but never in this combination.

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TABLE 1

Antimicrobial susceptibility of CT-Eco2 and E. coli BL21(DE3) with and without blaTEM-184 gene

The blaTEM-184 gene was amplified by PCR from CT-Eco2 using the specific primers TEM-for 5′-GGGGGCATATGATGAGTATTCAACATTTCCGT-3′ and TEM-rev 5′-GGGGGGGATCCTTACCAATGCTTAATCAGTGA-3′. The amplicon, after digestion with NdeI and BamHI (restriction sites underlined), was cloned in the pET-9(a) (Agilent Technologies, Santa Clara, CA) and pLB-II (7) vectors to yield recombinant plasmids pET-TEM-184 and pLB-TEM-184, respectively.

The TEM-184 enzyme was purified from a stationary-phase culture of E. coli BL21(DE3)/pET-TEM-184 grown aerobically at 37°C in 1.2 liters of tryptic soy broth containing kanamycin (50 μg/ml) as follows. Cells were collected by centrifugation (8,900 × g for 10 min), resuspended in 30 ml of 20 mM Tris-HCl, pH 7.4, and disrupted by sonication (5 times for 60 s each time at 60 W, on ice). After ultracentrifugation at 105,000 × g for 1 h, the cleared supernatant was loaded onto a Q-Sepharose FF column (bed volume, 100 ml) equilibrated with 20 mM Tris-HCl buffer (pH 7.4) and eluted with a linear NaCl gradient (0 to 1 M) in 20 mM Tris-HCl buffer (pH 7.4). The β-lactamase-containing fractions were pooled, concentrated by Centricon (cutoff, 10 kDa), and loaded on a Superdex 200 gel filtration column (XK 16/40; GE Healthcare, Milan, Italy) equilibrated with sodium-phosphate buffer 25 mM, pH 7.0 (buffer A). The eluted β-lactamase-containing fractions (5 ml) were collected, and the enzyme preparation was estimated to be >95% pure by SDS-PAGE (data not shown). Kinetic parameters were determined at 25°C in buffer A using a Lambda 25 spectrophotometer (PerkinElmer, Monza, Italy) as described previously (8). The Km, kcat, and Ki values were calculated using the equations reported by De Meester et al. (9).

In SDS-PAGE, the purified TEM-184 enzyme showed a molecular mass of 28.7 kDa. The isoelectric point, determined by isoelectric focusing, was 5.8.

TEM-184 was able to efficiently hydrolyze penicillins, ceftazidime, and aztreonam, which was one of the best substrates. Lower catalytic efficiencies, due to lower kcat and in some cases higher Km values, were detected for cefotaxime, cefazolin, and cefepime (Table 2). Clavulanic acid, tazobactam, and avibactam were overall good inhibitors of TEM-184, with Ki values of 0.24, 0.38, and 0.59 μM, respectively. Table 2 compares the Km, kcat, and kcat/Km values of TEM-184 with those of TEM-87 (E104K, R164C, M182T), TEM-107 (E104K, R164H, M182T, G238S), and TEM-149 (E104K, R164S, M182T, E240V) ESBLs (10–12), with which TEM-184 showed some amino acid similarities (Fig. 1). Compared with TEM-87 and TEM-149, TEM-184 showed higher Km values for ceftazidime, cefepime, and piperacillin. TEM-184 showed higher kcat and kcat/Km values for aztreonam than those observed for TEM variants reported in Table 2. Other TEM variants (TEM-63, TEM-131, TEM-177, TEM-205, TEM-211) have similar amino acid substitutions, but kinetic constants are not available.

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TABLE 2

Kinetic parameters of TEM-184 compared with TEM-1, TEM-10, TEM-87, TEM-107, and TEM-149 ESBLs

FIG 1
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FIG 1

Sequence alignment of TEM-184 with sequences of TEM-87 (accession no. AF250872), TEM-107 (accession no. AY101764), and TEM-149 (accession no. DQ369751). Top, secondary structure annotation of TEM-1 (PDB-ID 1M40). Arrows, β-strands; spirals, α-helices; red boxes, conserved position; red letters, similar residues. Aligned sequence was made using EsPrit (v.3.0).

Expression of TEM-184 in E. coli BL21(DE3), transformed with recombinant plasmid pLB-TEM-184, conferred resistance to piperacillin, ceftazidime, and aztreonam. On the other hand, the strain was intermediate to cefepime and remained susceptible to cefotaxime and β-lactam/β-lactamase inhibitor combinations, including piperacillin-tazobactam, ceftazidime-avibactam, and aztreonam-avibactam. MIC values of TEM-184 were similar to those of TEM-87 and TEM-149, with high values for piperacillin, ceftazidime, and aztreonam and low values for cefepime.

With the exception of I127V, all substitutions in TEM-184 were well described in TEM-type ESBLs. Residue Q6K in the signal peptide may have a role in efficient protein secretion across the membrane (13). Residue K104 seems to improve the catalytic activities of ESBLs against ceftazidime and aztreonam (14). Residue 164 is located in the omega loop and usually makes a salt bond and a hydrogen bond with D179; when the arginine is replaced by serine, the omega loop becomes more flexible because of the elimination of the electrostatic attraction between residues 164 and D179, allowing for better accommodation of bulky β-lactam substituents (14). The M182T mutation acts as a global suppressor of β-lactamase substitution that stabilizes the enzyme (15). This substitution has been identified in both ESBLs and inhibitor-resistant enzymes, and, when it is present in combination with R164S, it exerts a positive effect on TEM variants. Residue I127V was found in TEM-80 (also called IRT-24), which is resistant to inhibitors but also carries the M69L and N276D substitutions (16). In fact, as demonstrated by Arpin et al. (16), the substitution of I127V alone does not affect the inhibitor-resistant profile of the enzyme. Amino acid 127 is located at the end of the α3 helix (Fig. 1), and it is close to lysine 73. The lack of a methyl group at this position in valine 127 might result in a conformational alteration of the active site, which, in TEM-184, may increase the ability to hydrolyze aztreonam but is deleterious toward cefepime, cefotaxime, and cefazolin. It would be interesting to further test this hypothesis by site-directed mutagenesis experiments.

Accession number(s).The sequence for TEM-184 has been deposited in the GenBank database under accession number FR848831.

ACKNOWLEDGMENT

We have no conflicts of interest to declare.

FOOTNOTES

    • Received 6 April 2018.
    • Returned for modification 2 May 2018.
    • Accepted 19 June 2018.
    • Accepted manuscript posted online 25 June 2018.

REFERENCES

  1. 1.↵
    1. Philippon A,
    2. Labia R,
    3. Jacoby G
    . 1989. Extended-spectrum β-lactamases. Antimicrob Agents Chemother 33:1131–1136. doi:10.1128/AAC.33.8.1131.
    OpenUrlFREE Full Text
  2. 2.↵
    1. Bradford PA,
    2. Cherubin CE,
    3. Idemyor V,
    4. Rasmussen BA,
    5. Bush K
    . 1994. 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 38:761–766. doi:10.1128/AAC.38.4.761.
    OpenUrlAbstract/FREE Full Text
  3. 3.↵
    European Committee on Antimicrobial Susceptibility Testing (EUCAST). 2016. EUCAST guideline for the detection of resistance mechanisms and specific resistances of clinical and/or epidemiological importance, version 2.0, 2016. http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Resistance_mechanisms/EUCAST_detection_of_resistance_mechanisms_170711.pdf.
  4. 4.↵
    1. Aung MS,
    2. San N,
    3. Maw WW,
    4. San T,
    5. Urushibara N,
    6. Kawaguchiya M,
    7. Sumi A,
    8. Kobayashi N
    . 2018. Prevalence of extended-spectrum ß-lactamase and carbapenemase genes in clinical isolates of Escherichia coli in Myanmar: dominance of blaNDM-5 and emergence of blaOXA-181. Microb Drug Resist. doi:10.1089/mdr.2017.0387.
    OpenUrlCrossRef
  5. 5.↵
    1. Lee CS,
    2. Hu F,
    3. Rivera JI,
    4. Doi Y
    . 2014. Escherichia coli sequence type 354 coproducing CMY-2 cephalosporinase and RmtE 16S rRNA methyltransferase. Antimicrob Agents Chemother 58:4246–4247. doi:10.1128/AAC.02627-14.
    OpenUrlFREE Full Text
  6. 6.↵
    1. Accogli M,
    2. Giani T,
    3. Monaco M,
    4. Giufrè M,
    5. García-Fernández A,
    6. Conte V,
    7. D'Ancona F,
    8. Pantosti A,
    9. Rossolini GM,
    10. Cerquetti M
    . 2014. Emergence of Escherichia coli ST131 sub-clone H30 producing VIM-1 and KPC-3 carbapenemases, Italy. J Antimicrob Chemother 69:2293–2296. doi:10.1093/jac/dku132.
    OpenUrlCrossRefPubMed
  7. 7.↵
    1. Borgianni L,
    2. Vandenameele J,
    3. Matagne A,
    4. Bini L,
    5. Bonomo RA,
    6. Frère JM,
    7. Rossolini GM,
    8. Docquier JD
    . 2010. Mutational analysis of VIM-2 reveals an essential determinant for metallo-β-lactamase stability and folding. Antimicrob Agents Chemother 54:3197–3204. doi:10.1128/AAC.01336-09.
    OpenUrlAbstract/FREE Full Text
  8. 8.↵
    1. Segel IH
    . 1976. Biochemical calculations, 2nd ed, p 236–241. John Wiley & Sons, New York.
  9. 9.↵
    1. De Meester F,
    2. Joris B,
    3. Reckinger G
    . 1987. Automated analysis of enzyme inactivation phenomena: application to β-lactamases and DD-peptidases. Biochem Pharmacol 36:2393–2403. doi:10.1016/0006-2952(87)90609-5.
    OpenUrlCrossRefPubMedWeb of Science
  10. 10.↵
    1. Perilli M,
    2. Segatore B,
    3. De Massis MR,
    4. Franceschini N,
    5. Bianchi C,
    6. Rossolini GM,
    7. Amicosante G
    . 2002. Characterization of a new extended-spectrum β-lactamase (TEM-87) isolated in Proteus mirabilis during an Italian survey. Antimicrob Agents Chemother 46:925–928. doi:10.1128/AAC.46.3.925-928.2002.
    OpenUrlAbstract/FREE Full Text
  11. 11.↵
    1. Lee K,
    2. Yum JH,
    3. Yong D,
    4. Jeong SH,
    5. Rossolini GM,
    6. Docquier JD,
    7. Chong Y
    . 2011. Biochemical characterization of the TEM-107 extended-spectrum β-lactamase in a Klebsiella pneumoniae isolate from South Korea. Antimicrob Agents Chemother 55:5930–5932. doi:10.1128/AAC.05341-11.
    OpenUrlAbstract/FREE Full Text
  12. 12.↵
    1. Perilli M,
    2. Celenza G,
    3. De Santis F,
    4. Pellegrini C,
    5. Forcella C,
    6. Rossolini GM,
    7. Stefani S,
    8. Amicosante G
    . 2008. E240V substitution increases catalytic efficiency toward ceftazidime in a new natural TEM-type extended spectrum β-lactamase (TEM-149) from Enterobacter aerogenes and Serratia marcescens clinical isolates. Antimicrob Agents Chemother 52:915–919. doi:10.1128/AAC.01028-07.
    OpenUrlAbstract/FREE Full Text
  13. 13.↵
    1. Inouye S,
    2. Soberon X,
    3. Franceschini T,
    4. Nakamura K,
    5. Itakura K,
    6. Inouye M
    . 1982. Role of positive charge on the amino-terminal region of the signal peptide in protein secretion across the membrane. Proc Natl Acad Sci U S A 79:3438–3441. doi:10.1073/pnas.79.11.3438.
    OpenUrlAbstract/FREE Full Text
  14. 14.↵
    1. Knox JR
    . 1995. Extended-spectrum and inhibitor-resistant TEM-type β-lactamases: mutations, specificity, and three-dimensional structure. Antimicrob Agents Chemother 39:2593–2601. doi:10.1128/AAC.39.12.2593.
    OpenUrlFREE Full Text
  15. 15.↵
    1. Huang W,
    2. Palzkill T
    . 1997. A natural polymorphism in beta-lactamase is a global suppressor. Proc Natl Acad Sci U S A 94:8801–8806. doi:10.1073/pnas.94.16.8801.
    OpenUrlAbstract/FREE Full Text
  16. 16.↵
    1. Arpin C,
    2. Labia R,
    3. Dubois V,
    4. Noury V,
    5. Souquet M,
    6. Quentin C
    . 2002. TEM-80, a novel inhibitor-resistant β-lactamase in a clinical isolate of Enterobacter cloacae. Antimicrob Agents Chemother 46:1183–1189. doi:10.1128/AAC.46.5.1183-1189.2002.
    OpenUrlAbstract/FREE Full Text
  17. 17.
    Clinical and Laboratory Standards Institute. 2018. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard—11th ed. CLSI document M07-A11. Clinical and Laboratory Standards Institute, Wayne, PA.
  18. 18.
    1. Raquet X,
    2. Lamotte-Brasseur J,
    3. Fonzé E,
    4. Goussard S,
    5. Courvalin P,
    6. Frère JM
    . 1994. TEM β-lactamase mutants hydrolysing third generation cephalosporins: a kinetic and molecular modelling analysis. J Mol Biol 244:625–639. doi:10.1006/jmbi.1994.1756.
    OpenUrlCrossRefPubMedWeb of Science
  • Copyright © 2018 American Society for Microbiology.

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TEM-184, a Novel TEM-Derived Extended-Spectrum β-Lactamase with Enhanced Activity against Aztreonam
Alessandra Piccirilli, Mariagrazia Perilli, Gianfranco Amicosante, Viola Conte, Carlo Tascini, Gian Maria Rossolini, Tommaso Giani
Antimicrobial Agents and Chemotherapy Aug 2018, 62 (9) e00688-18; DOI: 10.1128/AAC.00688-18

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TEM-184, a Novel TEM-Derived Extended-Spectrum β-Lactamase with Enhanced Activity against Aztreonam
Alessandra Piccirilli, Mariagrazia Perilli, Gianfranco Amicosante, Viola Conte, Carlo Tascini, Gian Maria Rossolini, Tommaso Giani
Antimicrobial Agents and Chemotherapy Aug 2018, 62 (9) e00688-18; DOI: 10.1128/AAC.00688-18
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KEYWORDS

ESBL
avibactam
inhibitors

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