Antimicrobial Resistance Reference Strains
The significant increase in the incidence of antibiotic resistance in bacteria observed in recent years represents a significant challenge to public health microbiology worldwide. Not least among these challenges are extended-spectrum β-lactamases (ESBLs) and carbapenemases among Enterobacteriaceae and other Gram-negative micro-organisms and vancomycin resistance among enterococci.
Public Health England’s Antimicrobial Resistance and Healthcare Associated Infections Reference Unit (AMRHAI) is the national reference laboratory responsible for the detection and investigation of antibiotic resistance, especially in healthcare associated bacterial pathogens, and offers molecular detection of the genetic determinants of certain key resistances.
NCTC, working in partnership with AMRHAI, offers a range of reference strains with characterised resistance mechanisms. These include:
- A range of ESBLs, including examples of all major CTX-M groups
- A range of carbapenemases, including examples of all of the 'big five', which dominate internationally, namely KPC, OXA-48 non-metallo-enzymes and IMP, NDM and VIM metallo-carbapenemases
- The first reported clinical isolates of vancomycin-resistant enterococci (VRE)16
- Several fully-sequenced (and published) multi-drug resistance plasmids
- Methicillin-resistant Staphylococcus aureus (MRSA) including the first reported (and whole genome sequenced) strain identified with a novel mecA homologue.
Strains with defined resistance mechanisms are manufactured in accordance with the requirements of ISO9001:2008 and undergo extensive quality control by NCTC and AMRHAI to confirm the characteristics of the strain as new batches are prepared, although plasmids are not resequenced.
Download a pdf version of the Antimicrobial Resistance Reference Strains available from NCTC (link opens in a new window)
You may also be interested in: Antimicrobial Susceptibility Controls
1. Penicillinase without Extended-Spectrum β-Lactamase (ESBL) Activity :
| Organism | NCTC® Strain Reference | Characteristics | Ref |
| Escherichia coli | NCTC 11560 | TEM-1 β-lactamase producer. British Society of Antimicrobial Chemotherapy recommended control strain | |
| Escherichia coli | NCTC 11954 | (ATCC35218) β-lactamase producing control strain | |
| Staphylococcus aureus | NCTC 11561 | β-lactamase producing control strain |
2. Extended-Spectrum β-Lactamases (ESBL):
2.1 TEM β-lactamases
| Organism | NCTC® Strain Reference | Characteristics | Ref |
| Escherichia coli | NCTC 13351 | TEM-3 ESBL – Transconjugant of strain isolated in Clermont Ferrand in 1985 | 1 |
| Escherichia coli | NCTC 13352 | TEM-10 ESBL – Transconjugant of original TEM-10 producer isolated in Chicago in 1988 | 2 |
2.2 SHV β-lactamases
| Organism | NCTC® Strain Reference | Characteristics | Ref |
| Klebsiella pneumoniae | NCTC 13368 | SHV-18 (ATCC 700603) |
2.3 CTX-M β-lactamases
| Organism | NCTC® Strain Reference | Characteristics | Ref |
| Escherichia coli | NCTC 13353 | Strain EO 487. CTX-M-15 ESBL producer. Control strain for group 1 blaCTX-M multiplex PCR assays | 3 |
| Escherichia coli | NCTC 13441 |
Strain EO 499. CTX-M-15 ESBL producer – Uropathogenic strain O25:H4 sequence type (ST) 131. Clinical isolate harbouring sequenced plasmid pEK499 (see NCTC 13400); Control strain for group 1 blaCTX-M multiplex PCR assays |
3 |
| Escherichia coli | NCTC 13400 | Strain Tr499= DH5α derivative. Source of pEK499 (fully sequenced plasmid GenBank Accession No EU935739) encoding CTX-M-15 enzyme. Fusion of type FII and FIA replicons, and harbours 10 antibiotic resistance genes (see catalogue entry for details) | 4 |
| Escherichia coli | NCTC 13451 | Strain J499 = J53 derivative. Source of pEK499 (fully sequenced plasmid GenBank Accession No EU935739) encoding CTX-M-15 enzyme. Fusion of type FII and FIA replicons, and harbours 10 antibiotic resistance genes (see catalogue entry for details) | 4 |
| Escherichia coli | NCTC 13450 | Strain Tr516 = DH5 α derivative. Source of pEK516 (fully sequenced plasmid GenBank Accession No EU935738), which encodes CTX-M-15 enzyme. Harbours 7 antibiotic resistance genes (see catalogue entry for details) | 4 |
| Escherichia coli | NCTC 13452 | Strain J204 = J53 derivative. Source of pEK204 (fully sequenced plasmid GenBank Accession No EU935740), encoding CTX-M-3 enzyme. Plasmid pEK204 (93,732-bp) belongs to incompatibility group IncI1, and harbours two antibiotic resistance genes (see catalogue entry for details) | 4 |
| Escherichia coli | NCTC 13461 | Strain harbours unsequenced blaCTX-M group 1 gene | 5 |
| Escherichia coli | NCTC 13462 | Strain harbours unsequenced blaCTX-M group 2 gene | 5 |
| Escherichia coli | NCTC 13463 | Strain harbours unsequenced blaCTX-M group 8 gene | 5 |
| Enterobacter cloacae | NCTC 13464 | Strain harbours unsequenced blaCTX-M group 9 gene | 5 |
| Klebsiella pneumoniae | NCTC 13465 | Strain harbours unsequenced blaCTX-M group 25 gene | 5 |
2.4 VEB β-lactamases
| Organism | NCTC® Strain Reference | Characteristics | Ref |
| Pseudomonas aeruginosa | NCTC 13437 | VIM-10; VEB-1 | 6 |
3. AmpC β-lactamases:
| Organism | NCTC® Strain Reference | Characteristics | Ref |
| Enterobacter cloacae | NCTC 13405 | Strain 684. Inducible AmpC β-lactamase, wild type. Control for AmpC detection tests. | |
| Enterobacter cloacae | NCTC 13406 | Strain 684-con. AmpC β-lactamase de-repressed (i.e. constitutive hyper-producing) mutant of NCTC 13405. Control for AmpC detection tests |
4. Carbapenemases
4.1 Class A Carbapenemase
| Organism | NCTC® Strain Reference | Characteristics | Ref |
| Klebsiella pneumoniae | NCTC 13438 | Member of the international ST258 clone producing KPC-3 carbapenemase | 7 |
4.2 Class B Carbapenemases (Metallo-β-lactamases):
| Organism | NCTC® Strain Reference | Characteristics | Ref |
| Pseudomonas aeruginosa | NCTC 13437 | VIM-10; VEB-1 | 6 |
| Klebsiella pneumoniae | NCTC 13439 | VIM-1; QnrS1 (outbreak strain) | 8 |
| Klebsiella pneumoniae | NCTC 13440 | VIM-1; QnrS1 (sporadic) | 8 |
| Klebsiella pneumoniae | NCTC 13443 | New Delhi Metallo-β-lactamase (NDM-1) | |
| Escherichia coli | NCTC 13476 | IMP-type (unsequenced) |
4.3 Class D Carbapenemases (OXA carbapenemases):
| Organism | NCTC® Strain Reference | Characteristics | Ref |
| Acinetobacter baumannii | NCTC 13301 | OXA-23 (also with OXA-51-like) | 9 |
| Acinetobacter baumannii | NCTC 13302 | OXA-25 (OXA-24/40-like) (also with OXA-51-like) | 9 |
| Acinetobacter baumannii | NCTC 13303 | OXA-26 (also with OXA-51-like) | 9 |
| Acinetobacter baumannii | NCTC 13304 | OXA-27 (also with OXA-51-like) | 9 |
| Acinetobacter baumannii | NCTC 13305 | (A 15) OXA-58 (also with OXA-51-like) | 10 |
| Acinetobacter baumannii | NCTC 13421 | OXA-23 Clone 2 (also with OXA-51-like) | 11,12 |
| Acinetobacter baumannii | NCTC 13424 | OXA 23 Clone 1 (also with OXA-51-like) | 11,12 |
| Acinetobacter baumannii | NCTC 13420 | SE Clone OXA-51-like | 11,12 |
| Acinetobacter baumannii | NCTC 13422 | NW Clone OXA-51-like | 13, 14,15 |
| Acinetobacter baumannii | NCTC 13423 | T strain (UK3) OXA-51-like | 13,14,15 |
| Klebsiella pneumoniae | NCTC 13442 | Sequence type 353 with OXA-48 | 17 |
5. Plasmid-mediated Fluoroquinolone Resistance (Qnr)
| Organism | NCTC® Strain Reference | Characteristics | Ref |
| Klebsiella pneumoniae | NCTC 13439 | VIM-1; QnrS1 (outbreak strain) | 8 |
| Klebsiella pneumoniae | NCTC 13440 | VIM-1; QnrS1 (sporadic) | 8 |
6. Vancomycin Resistant Enterococci
| Organism | NCTC® Strain Reference | Characteristics | Ref |
| Enterococcus faecalis | NCTC 12201 | VanA-type glycopeptide resistance, Erythromycin resistant | 16 |
| Enterococcus faecium | NCTC 12202 | VanA-type glycopeptide resistance | 16 |
| Enterococcus faecalis | NCTC 12203 | VanA-type glycopeptide resistance | 16 |
| Enterococcus faecium | NCTC 12204 | VanA-type glycopeptide resistance | 16 |
7. Multidrug Resistance Plasmids
| Organism | NCTC® Strain Reference | Characteristics | Ref |
| Escherichia coli | NCTC 13400 | Strain Tr499 = DH5α derivative. Source of pEK499 (fully sequenced plasmid GenBank Accession No EU935739). Fusion of type FII and FIA replicons, and harbours 10 antibiotic resistance genes (see catalogue entry for details) | 4 |
| Escherichia coli | NCTC 13451 | Strain J499 = J53 derivative. Source of pEK499 (fully sequenced plasmid GenBank Accession No EU935739). Fusion of type FII and FIA replicons, and harbours 10 antibiotic resistance genes (see catalogue entry for details) | 4 |
| Escherichia coli | NCTC 13450 | Strain Tr516 = DH5α derivative. Source of pEK516 (fully sequenced plasmid GenBank Accession No EU935738). Harbours 7 antibiotic resistance genes (see catalogue entry for details) | 4 |
| Escherichia coli | NCTC 13452 | Strain J204 = J53 derivative. Source of pEK204 (fully sequenced plasmid GenBank Accession No EU935740), encoding CTX-M-3 enzyme. Plasmid pEK204 (93,732-bp) belongs to incompatibility group IncI1, and harbours two antibiotic resistance genes (see catalogue entry for details) | 4 |
8. Methicillin-Resistant Staphylococcus aureus (MRSA)
| Organism | NCTC® Strain Reference | Characteristics | Ref |
| Staphylococcus aureus | NCTC 13142 | EMRSA-15 type strain. Epidemic MRSA from UK. control for mecA detection tests. | 18 |
| Staphylococcus aureus | NCTC 13552 | Strain LGA251. Control for mecA homologue (soon to be assignedmecC) detection tests. Isolated from bulk milk. | 19 |
References
1. Sirot D, Sirot J, Labia R. Transferable resistance to third generation cephalosporins in clinical isolates of Klebsiella pneumoniae. J Antimicrob. Chemother. 1987, 20, 323.
2. Quinn JP, Miyashiro D, Sahm D, Flamm R, Bush Kl. Novel plasmid-mediated beta-lactamase (TEM-10) conferring selective resistance to ceftazidime and axtreonam in clinical isolates of Klebsiella pneumoniae, Antimicrob Agents Chemother 1989, 33(9), 1451-1456
3. Woodford N Ward, M.E.,Kaufmann, M.E.,Turton, J.,Fagan, EJ,James, D,Johnson, AP,Pike, R.,Warner, M.,Cheasty, T.Pearson, A.,Harry, S.,Leach, J.B.,Loughrey, A.,Lowes, J.A.,Warren, R.E.,Livemore, D.M. Community and hospital spread of Escherichia coli producing CTX-M extended-spectrum β-lactamases in the UK. J Antimicrob Chemother 2004, 54, 735-43.
4. Woodford N, Carattilo A, Karisik E, Underwood A, Ellington MJ, Livermore, D M. Complete nucleotide sequences of plasmids pEK204, pEK499, and pEK516, encoding CTX-M enzymes in three major Escherichia coli lineages from the United Kingdom, all belonging to the international O25:H4-ST131 clone. Antimicrob Agents Chemother. 2009; 53(10), 4472-4482
5. Woodford N, Fagan EJ, Ellington MJ. Multiplex PCR for rapid detection of genes encoding CTX-M extended-spectrum (beta)-lactamases. J Antimicrob Chemother. 2006; 57:154-5.
6. Woodford N, Zhang J, Kaufmann ME, Yarde S, Tomas Mdel M, Faris C, Vardhan MS, Dawson S, Cotterill SL, Livermore DM. Detection of Pseudomonas aeruginosa isolates producing VEB-type extended-spectrum beta-lactamases in the United Kingdom. J Antimicrob Chemother. 2008,;62(6):1265-8.
7. Woodford N, Zhang J, Warner M, Kaufmann ME, Matos J, Macdonald A, Brudney D, Sompolinsky D, Navon-Venezia S, Livermore DM. Arrival of Klebsiella pneumoniae producing KPC carbapenemase in the United Kingdom. J Antimicrob Chemother. 2008; 62(6):1261-4.
8. Aschbacher R, Doumith M, Livermore DM, Larcher C, Woodford N. Linkage of acquired quinolone resistance (qnrS1) and metallo-beta-lactamase (blaVIM-1) genes in multiple species of Enterobacteriaceae from Bolzano, Italy. J Antimicrob Chemother. 2008 Mar;61(3):515-23.
9. Afzal-Shah M, Woodford N, Livermore DM. Characterization of OXA-25, OXA-26 and OXA-27, molecular class D beta-lactamases associated with carbapenem resistance in clinical isolates of Acinetobacter baumannii.Antimicrob Agents Chemother. 2001 Feb;45(2):583-8
10. Coelho J, Woodford N, Afzal-Shah M, Livermore D. Occurrence of OXA-58-like carbapenemases in Acinetobacter spp. collected over 10 years in three continents. Antimicrob Agents Chemother. 2006, 50(2):756-8.
11. Turton JF, Kaufmann ME, Warner M, Coelho J, Dijkshoorn L, van der Reijden T, Pitt TL. A prevalent, multiresistant clone of Acinetobacter baumannii in Southeast England. J Hosp Infect. 2004; 58(3):170-9.
12. Coelho JM, Turton JF, Kaufmann ME, Glover J, Woodford N, Warner M, Palepou MF, Pike R, Pitt TL, Patel BC, Livermore DM. Occurrence of carbapenem-resistant Acinetobacter baumannii clones at multiple hospitals in London and Southeast England. J Clin Microbiol. 2006, 44(10):3623-7.
13. Turton JF, Kaufmann ME, Glover J, Coelho JM, Warner M, Pike R, Pitt TL. Detection and typing of integrons in epidemic strains of Acinetobacter baumannii found in the United Kingdom. J Clin Microbiol. 2005; 43(7):3074-82.
14. Turton JF, Kaufmann ME, Gill MJ, Pike R, Scott PT, Fishbain J, Craft D, Deye G, Riddell S, Lindler LE, Pitt TL. Comparison of Acinetobacter baumannii isolates from the United Kingdom and the United States that were associated with repatriated casualties of the Iraq conflict. J Clin Microbiol. 2006; 44(7):2630-4.
15. Turton JF, Gabriel SN, Valderrey C, Kaufmann ME, Pitt TL. Use of sequence-based typing and multiplex PCR to identify clonal lineages of outbreak strains of Acinetobacter baumannii. Clin Microbiol Infect. 2007; 13(8):807-
16. Uttley AHC, George RC, Naidoo J, Woodford N, Johnson AP, Collins CH, Morrison D, Gilfillan AJ, Fitch,LE, Heptonstall J. High level Vancomycin-resistant Enterococci causing hospital infections. Epidem. Inf. (1989) 103; 173-181
17. Dimou et al. J Antimicrob Chemother. 2012 Jul; 67(7) 1660-5
18. O’Neill GL, Murchan S, Gil-Setas A, Aucken HM. Identification and characterization of phage variants of a strain of epidemic methicillin-resistant Staphylococcus aureus (EMRSA-15). J Clin Microbiol 2001; 39:1540-8.
19. García-Álvarez L, Holden MTG, Lindsay H, Webb CR, Brown DFJ, Curran MD, Walpole E, Brooks K, Pickard DJ, Teale C, Parkhill J, Bentley SD, Edwards GF, Girvan EK, Kearns AM, Pichon B, Hill R, Larsen AR, Skov RL, Peacock SJ, Maskell DJ, Holmes MA. Meticillin-resistant Staphylococcus aureus with a novel mecA homologue in human and bovine populations in the UK and Denmark: a descriptive study. Lancet Infect Dis 2011;11(8):595-603.
Useful Links
Antimicrobial Resistance and Healthcare Associated Infections Reference Unit (AMRHAI)