trimethoprim resistance


Summary: Nonsusceptibility of bacteria to the action of TRIMETHOPRIM.

Top Publications

  1. Petersen A, Guardabassi L, Dalsgaard A, Olsen J. Class I integrons containing a dhfrI trimethoprim resistance gene cassette in aquatic Acinetobacter spp. FEMS Microbiol Lett. 2000;182:73-6 pubmed
    ..To our knowledge, this is the first report and characterisation of an integron in environmental bacteria. ..
  2. Skold O. Resistance to trimethoprim and sulfonamides. Vet Res. 2001;32:261-73 pubmed
    ..This means that susceptibility will not return after suspending the use of sulfonamide and trimethoprim. ..
  3. Brolund A, Sundqvist M, Kahlmeter G, Grape M. Molecular characterisation of trimethoprim resistance in Escherichia coli and Klebsiella pneumoniae during a two year intervention on trimethoprim use. PLoS ONE. 2010;5:e9233 pubmed publisher
    b>Trimethoprim resistance is increasing in Enterobacteriaceae. In 2004-2006 an intervention on trimethoprim use was conducted in Kronoberg County, Sweden, resulting in 85% reduction in trimethoprim prescriptions...
  4. Podnecky N, Wuthiekanun V, Peacock S, Schweizer H. The BpeEF-OprC efflux pump is responsible for widespread trimethoprim resistance in clinical and environmental Burkholderia pseudomallei isolates. Antimicrob Agents Chemother. 2013;57:4381-6 pubmed publisher
    ..Here, we demonstrate that trimethoprim resistance is widespread in clinical and environmental isolates from northeast Thailand and northern Australia...
  5. Kadlec K, Schwarz S. Identification of a novel trimethoprim resistance gene, dfrK, in a methicillin-resistant Staphylococcus aureus ST398 strain and its physical linkage to the tetracycline resistance gene tet(L). Antimicrob Agents Chemother. 2009;53:776-8 pubmed publisher
    A novel trimethoprim resistance gene, designated dfrK, was detected in close proximity to the tetracycline resistance gene tet(L) on the ca...
  6. Penteado A, Castanheira M, Pignatari A, Guimarães T, Mamizuka E, Gales A. Dissemination of bla(IMP-1)-carrying integron In86 among Klebsiella pneumoniae isolates harboring a new trimethoprim resistance gene dfr23. Diagn Microbiol Infect Dis. 2009;63:87-91 pubmed publisher
    ..Eight strains from the same hospital also carried another class 1 integron harboring a new trimethoprim resistance gene (dfr23) that was chromosomally embedded...
  7. Agersø Y, Peirano G, Aarestrup F. dfrA25, a novel trimethoprim resistance gene from Salmonella Agona isolated from a human urine sample in Brazil. J Antimicrob Chemother. 2006;58:1044-7 pubmed
    To describe a novel trimethoprim resistance gene, designated dfrA25, which was detected as a gene cassette within a class 1 integron in Salmonella Agona...
  8. Sundqvist M, Geli P, Andersson D, Sjölund Karlsson M, Runehagen A, Cars H, et al. Little evidence for reversibility of trimethoprim resistance after a drastic reduction in trimethoprim use. J Antimicrob Chemother. 2010;65:350-60 pubmed publisher
    ..The intervention was performed on a 14 year baseline of monthly data on trimethoprim resistance and consumption. A three-parameter mathematical model was used to analyse the intervention effect...
  9. Sundstrom L, Swedberg G, Skold O. Characterization of transposon Tn5086, carrying the site-specifically inserted gene dhfrVII mediating trimethoprim resistance. J Bacteriol. 1993;175:1796-805 pubmed
    Two different enteric plasmids of widely separate origins were observed to carry a new 15.3-kb trimethoprim resistance transposon, Tn5086, also mediating resistance to mercuric ions and to a low level of sulfonamide...

More Information


  1. Apisiridej S, Leelaporn A, Scaramuzzi C, Skurray R, Firth N. Molecular analysis of a mobilizable theta-mode trimethoprim resistance plasmid from coagulase-negative staphylococci. Plasmid. 1997;38:13-24 pubmed publisher 8 kb in length and possesses a composite structure consisting of an IS257-flanked segment mediating trimethoprim resistance (Tpr), and regions responsible for replication and mobilization of the plasmid...
  2. Lee J, Oh J, Cho J, Park J, Kim J, Seol S, et al. The prevalence of trimethoprim-resistance-conferring dihydrofolate reductase genes in urinary isolates of Escherichia coli in Korea. J Antimicrob Chemother. 2001;47:599-604 pubmed
    One-hundred and twenty-two urinary isolates of Escherichia coli were studied for trimethoprim resistance. Seventy-seven (63.1%) of the 122 isolates were found to be resistant to trimethoprim...
  3. Rouch D, Messerotti L, Loo L, Jackson C, Skurray R. Trimethoprim resistance transposon Tn4003 from Staphylococcus aureus encodes genes for a dihydrofolate reductase and thymidylate synthetase flanked by three copies of IS257. Mol Microbiol. 1989;3:161-75 pubmed
    b>Trimethoprim resistance mediated by the Staphylococcus aureus multi-resistance plasmid pSK1 is encoded by a structure with characteristics of a composite transposon which we have designated Tn4003...
  4. Queener S, Cody V, Pace J, Torkelson P, Gangjee A. Trimethoprim resistance of dihydrofolate reductase variants from clinical isolates of Pneumocystis jirovecii. Antimicrob Agents Chemother. 2013;57:4990-8 pubmed publisher
    ..jirovecii produce variant forms of DHFR that are resistant to trimethoprim and may contribute to clinically observed failures of standard therapy or prophylaxis. ..
  5. Kumar A, Mukherjee S, Chakraborty R. Characterization of a novel trimethoprim resistance gene, dfrA28, in class 1 integron of an oligotrophic Acinetobacter johnsonii strain, MB52, isolated from River Mahananda, India. Microb Drug Resist. 2010;16:29-37 pubmed publisher
    ..4% amino acid identity with DfrA1. A gene for streptomycin resistance, aminoglycoside adenyl transferase aadA1, was located downstream of dfrA28. Phylogenetic analysis of MB52 identified it as a strain of Acinetobacter johnsonii. ..
  6. Blahna M, Zalewski C, Reuer J, Kahlmeter G, Foxman B, Marrs C. The role of horizontal gene transfer in the spread of trimethoprim-sulfamethoxazole resistance among uropathogenic Escherichia coli in Europe and Canada. J Antimicrob Chemother. 2006;57:666-72 pubmed
    ..b>Trimethoprim resistance gene distributions showed no regional dependency (P = 0.84)...
  7. Mangin D, Toop L, Chambers S, Ikram R, Harris B. Increased rates of trimethoprim resistance in uncomplicated urinary tract infection: cause for concern?. N Z Med J. 2005;118:U1726 pubmed
    To assess changes in trimethoprim resistance over 2 years in bacteria causing uncomplicated urinary tract infections (UTIs) presenting to a representative group of general practitioners (GPs) in Christchurch...
  8. White P, McIver C, Deng Y, Rawlinson W. Characterisation of two new gene cassettes, aadA5 and dfrA17. FEMS Microbiol Lett. 2000;182:265-9 pubmed
    ..Cloning and expression of the cassette region demonstrated that dfrA17 conferred high level resistance to trimethoprim but aadA5 conferred resistance to spectinomycin but not to streptomycin. ..
  9. Dale G, Broger C, D Arcy A, Hartman P, DeHoogt R, Jolidon S, et al. A single amino acid substitution in Staphylococcus aureus dihydrofolate reductase determines trimethoprim resistance. J Mol Biol. 1997;266:23-30 pubmed
    ..Knowledge of the resistance mechanism at a molecular level could help in the design of antibacterials active against multi-resistant Staphylococcus aureus (MRSA), one of todays most serious problems in clinical infectology. ..
  10. Kehrenberg C, Schwarz S. dfrA20, A novel trimethoprim resistance gene from Pasteurella multocida. Antimicrob Agents Chemother. 2005;49:414-7 pubmed publisher
    A novel trimethoprim resistance gene, designated dfrA20, was detected on the 11-kb plasmid pCCK154 from Pasteurella multocida. The dfrA20 gene codes for a dihydrofolate reductase of 169 amino acids...
  11. Seputiene V, Povilonis J, Ruzauskas M, Pavilonis A, Suziedeliene E. Prevalence of trimethoprim resistance genes in Escherichia coli isolates of human and animal origin in Lithuania. J Med Microbiol. 2010;59:315-22 pubmed publisher
    ..However, TMP resistance in some of the isolates was found to be mediated by non-integron-associated dfrA8 and dfrA14 genes, indicating the existence of alternative sources for the spread of resistance. ..
  12. Grape M, Sundstrom L, Kronvall G. Two new dfr genes in trimethoprim-resistant integron-negative Escherichia coli isolates. Antimicrob Agents Chemother. 2007;51:1863-4 pubmed
    ..The dfrA24 gene was not associated with known mobile elements, while dfrA26 was associated with the CR1 common region. ..
  13. Grape M, Motakefi A, Pavuluri S, Kahlmeter G. Standard and real-time multiplex PCR methods for detection of trimethoprim resistance dfr genes in large collections of bacteria. Clin Microbiol Infect. 2007;13:1112-8 pubmed
    ..n = 368) with the two multiplex methods revealed that the five dfr genes accounted for 75-86% of trimethoprim resistance. The standard mPCR is useful and accessible for most laboratories, while the real-time mPCR requires ..
  14. Wei Q, Jiang X, Yang Z, Chen N, Chen X, Li G, et al. dfrA27, a new integron-associated trimethoprim resistance gene from Escherichia coli. J Antimicrob Chemother. 2009;63:405-6 pubmed publisher
  15. Huovinen P. Trimethoprim resistance. Antimicrob Agents Chemother. 1987;31:1451-6 pubmed
  16. L pez M, Kadlec K, Schwarz S, Torres C. First detection of the staphylococcal trimethoprim resistance gene dfrK and the dfrK-carrying transposon Tn559 in enterococci. Microb Drug Resist. 2012;18:13-8 pubmed publisher
    The trimethoprim resistance gene dfrK has been recently described in Staphylococcus aureus, but so far has not been found in other bacteria. A total of 166 enterococci of different species (E. faecium, E. faecalis, E. hirae, E. durans, E...
  17. Bertsch D, Uruty A, Anderegg J, Lacroix C, Perreten V, Meile L. Tn6198, a novel transposon containing the trimethoprim resistance gene dfrG embedded into a Tn916 element in Listeria monocytogenes. J Antimicrob Chemother. 2013;68:986-91 pubmed publisher
    ..transposon from the clinical Listeria monocytogenes strain TTH-2007, which contains the tetracycline and trimethoprim resistance genes tet(M) and dfrG, respectively, and to assess its transferability in vitro and in situ...
  18. Parsons Y, Hall R, Stokes H. A new trimethoprim resistance gene, dhfrX, in the In7 integron of plasmid pDGO100. Antimicrob Agents Chemother. 1991;35:2436-9 pubmed
    A new trimethoprim resistance determinant, designated dhfrX, was identified in the In7 integron of pDGO100...
  19. Thomson C. Trimethoprim and brodimoprim resistance of gram-positive and gram-negative bacteria. J Chemother. 1993;5:458-64 pubmed
    ..Whilst this probably results from the continuing evolution of resistance it can also be partly attributed to more discriminatory methods for studying these enzymes. ..
  20. Grape M, Sundstrom L, Kronvall G. Sulphonamide resistance gene sul3 found in Escherichia coli isolates from human sources. J Antimicrob Chemother. 2003;52:1022-4 pubmed
    ..Sulphonamide resistance gene sul3, which is widespread among pigs in Switzerland, has now also been identified in two different clinical isolates of Escherichia coli, located in urinary tract infections in patients in Sweden. ..
  21. Sundstr m L, Jansson C, Bremer K, Heikkil E, Olsson Liljequist B, Sk ld O. A new dhfrVIII trimethoprim-resistance gene, flanked by IS26, whose product is remote from other dihydrofolate reductases in parsimony analysis. Gene. 1995;154:7-14 pubmed
    A new plasmid-borne gene, dhfrVIII, encoding high-level trimethoprim resistance (TpR) was found in an intestinal Escherichia coli. It seems to be a widely occurring mediator of TpR. Among 973 examined TpR E...
  22. Steinke D, Seaton R, Phillips G, MacDonald T, Davey P. Factors associated with trimethoprim-resistant bacteria isolated from urine samples. J Antimicrob Chemother. 1999;43:841-3 pubmed
    ..Prior oestrogen exposure was associated with trimethoprim resistance. There were no associations found for diabetes or prior corticosteroid exposure...
  23. Dicks L, Fraser T, ten Doeschate K, Van Reenen C. Lactic acid bacteria population in children diagnosed with human immunodeficiency virus. J Paediatr Child Health. 2009;45:567-72 pubmed publisher
    ..A number of strains were resistant to sulphamethoxazole and may be used as probiotics to correct the imbalance in lactic acid bacteria. ..
  24. den Heijer C, Beerepoot M, Prins J, Geerlings S, Stobberingh E. Determinants of antimicrobial resistance in Escherichia coli strains isolated from faeces and urine of women with recurrent urinary tract infections. PLoS ONE. 2012;7:e49909 pubmed publisher
    ..coli resistance. Previous antibiotic use and UTI history were associated with urine E. coli resistance and age was a predictor of faecal E. coli resistance. These associations could best be explained by cumulative antibiotic use. ..
  25. Du X, Shen Z, Wu B, Xia S, Shen J. Characterization of class 1 integrons-mediated antibiotic resistance among calf pathogenic Escherichia coli. FEMS Microbiol Lett. 2005;245:295-8 pubmed publisher
    ..coli isolates in the Beijing surrounding region in China, which may provide important and useful surveillance information reflecting specific antibiotic selective pressure...
  26. Tvede M, Høiby N, Larsen L, Raben A, Astrup A. [Antibiotic resistance of E coli isolated from healthy persons]. Ugeskr Laeger. 2001;163:4868-71 pubmed
    ..The consequences of the results for empiric antibiotic treatment of, for instance, urinary tract infection are discussed. ..
  27. Stratchounski L, Kretchikova O, Reshedko G, Stetsiouk O, Kandalov M, Egorova O, et al. Antimicrobial susceptibility of nasopharyngeal isolates of Haemophilus influenzae from healthy children in day-care centres: results of multicentre study in Russia. Int J Antimicrob Agents. 2001;18:347-51 pubmed
    ..The antimicrobial resistance profiles varied in different centres. The clinical use of trimethoprim-sulphamethoxazole should be restricted because of the high resistance of H. influenzae to antifolate compounds. ..
  28. Wright S, Wrenn K, Haynes M. Trimethoprim-sulfamethoxazole resistance among urinary coliform isolates. J Gen Intern Med. 1999;14:606-9 pubmed
    ..Clinicians should consider these findings when deciding on antimicrobial therapy for patients with urinary tract infections. ..
  29. Chang C, Chang L, Chang Y, Lee T, Li Y, Chang S. Two new gene cassettes, dfr17 (for trimethoprim resistance) and aadA4 (for spectinomycin/streptomycin resistance), inserted in an Escherichia coli class 1 integron. J Antimicrob Chemother. 2000;46:87-9 pubmed
    ..The dfr17 cassette encodes trimethoprim resistance and has 91% identity with the dfrVII dihydrofolate reductase gene...
  30. Sanchez G, Master R, Karlowsky J, Bordon J. In vitro antimicrobial resistance of urinary Escherichia coli isolates among U.S. outpatients from 2000 to 2010. Antimicrob Agents Chemother. 2012;56:2181-3 pubmed publisher
    ..8% to 1.6%) and ceftriaxone (0.2% to 2.3%) showed minimal change. From 2000 to 2010, the antimicrobial resistance of urinary E. coli isolates to ciprofloxacin and TMP-SMX among outpatients increased substantially. ..
  31. Lovgren M, Dell Acqua L, Palacio R, Echaniz Aviles G, Soto Noguerón A, Castaneda E, et al. Determination of trimethoprim-sulfamethoxazole resistance in Streptococcus pneumoniae by using the E test with Mueller-Hinton agar supplemented with sheep or horse blood may be unreliable. The Pneumococcal Study Group. J Clin Microbiol. 1999;37:215-7 pubmed
    ..9 and 13.6%, respectively, with horse blood as the supplement. Significant interlaboratory variability was observed. E test may not be a reliable method for determining the resistance of pneumococci to trimethoprim-sulfamethoxazole. ..
  32. Steinke D, Seaton R, Phillips G, MacDonald T, Davey P. Prior trimethoprim use and trimethoprim-resistant urinary tract infection: a nested case-control study with multivariate analysis for other risk factors. J Antimicrob Chemother. 2001;47:781-7 pubmed
    b>Trimethoprim resistance is increasingly prevalent in community-acquired urinary infections...
  33. Gupta K. Addressing antibiotic resistance. Dis Mon. 2003;49:99-110 pubmed
    ..In areas where resistance to TMP-SMX exceeds this rate, alternative agents need to be considered. ..
  34. Navarro Martínez M, Navarro Perán E, Cabezas Herrera J, Ruiz Gómez J, García Cánovas F, Rodriguez Lopez J. Antifolate activity of epigallocatechin gallate against Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 2005;49:2914-20 pubmed
    ..We conclude that the mechanism of action of epigallocatechin gallate on S. maltophilia is related to its antifolate activity. ..
  35. Schneider P, Hawser S, Islam K. Iclaprim, a novel diaminopyrimidine with potent activity on trimethoprim sensitive and resistant bacteria. Bioorg Med Chem Lett. 2003;13:4217-21 pubmed
    ..This compound is active against methicillin, TMP and vancomycin resistant strains. Arpida Ltd. is developing Iclaprim for serious hospital infections from Gram-positive pathogens and respiratory tract infections. ..
  36. Miller L, Tang A. Treatment of uncomplicated urinary tract infections in an era of increasing antimicrobial resistance. Mayo Clin Proc. 2004;79:1048-53; quiz 1053-4 pubmed
    ..We review options for management of uncomplicated UTIs in light of these considerations. ..
  37. Ostroff S, Harrison L, Khallaf N, Assaad M, Guirguis N, Harrington S, et al. Resistance patterns of Streptococcus pneumoniae and Haemophilus influenzae isolates recovered in Egypt from children with pneumonia. The Antimicrobial Resistance Surveillance Study Group. Clin Infect Dis. 1996;23:1069-74 pubmed
    ..9% and 100%, respectively. Although most S. pneumoniae and H. influenzae strains associated with childhood pneumonia in Cairo were susceptible to penicillins and co-trimoxazole, antimicrobial resistance did not occur. ..
  38. Hartman P, Stähli M, Kocher H, Then R. N-terminal amino acid sequence of the chromosomal dihydrofolate reductase purified from trimethoprim-resistant Staphylococcus aureus. FEBS Lett. 1988;242:157-60 pubmed
    ..Its N-terminal amino acid sequence, determined up to the first 35 amino acids, showed 69% homology with the Escherichia coli DHFR. ..
  39. Kadlec K, Kehrenberg C, Schwarz S. Molecular basis of resistance to trimethoprim, chloramphenicol and sulphonamides in Bordetella bronchiseptica. J Antimicrob Chemother. 2005;56:485-90 pubmed
    ..The aim of this study was to identify genes coding for trimethoprim resistance present in porcine B...
  40. Le T, Miller L. Empirical therapy for uncomplicated urinary tract infections in an era of increasing antimicrobial resistance: a decision and cost analysis. Clin Infect Dis. 2001;33:615-21 pubmed
    ..Treatment guidelines for empirical treatment of UTIs may need modification, and the threshold trigger for empirical FQ use should be raised to >20% TMP-SMZ resistance. ..
  41. Manninen R, Huovinen P, Nissinen A. Increasing antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in Finland. J Antimicrob Chemother. 1997;40:387-92 pubmed
    ..4% of H. influenzae and 0.7% of M. catarrhalis. Frequencies of azithromycin resistance were 3.0% in S. pneumoniae and 1.6% in H. influenzae, and those of tetracycline resistance were 6.7% in S. pneumoniae and 1.2% in H. influenzae. ..
  42. Livermore D, Stephens P, Weinberg J, Johnson A, Gifford T, Northcott D, et al. Regional variation in ampicillin and trimethoprim resistance in Escherichia coli in England from 1990 to 1997, in relation to antibacterial prescribing. J Antimicrob Chemother. 2000;46:411-22 pubmed
    ..We reviewed ampicillin and trimethoprim resistance rates from 1990 to 1997 for Escherichia coli, which is the species reported most frequently from these ..
  43. Adrian P, du Plessis M, Klugman K, Amyes S. New trimethoprim-resistant dihydrofolate reductase cassette, dfrXV, inserted in a class 1 integron. Antimicrob Agents Chemother. 1998;42:2221-4 pubmed
    The nucleotide sequence of a plasmid-borne trimethoprim resistance gene from a commensal fecal Escherichia coli isolate revealed a new dihydrofolate reductase gene, dfrXV, which occurred as a gene cassette integrated in a site-specific ..
  44. Ladhani S, Gransden W. Increasing antibiotic resistance among urinary tract isolates. Arch Dis Child. 2003;88:444-5 pubmed
    ..In particular, up to a third of E coli isolates from children in the community and almost two thirds of E coli isolates from children with underlying renal disease may be resistant to trimethoprim. ..
  45. Gassama Sow A, Aidara Kane A, Barraud O, Gatet M, Denis F, Ploy M. High prevalence of trimethoprim-resistance cassettes in class 1 and 2 integrons in Senegalese Shigella spp isolates. J Infect Dev Ctries. 2010;4:207-12 pubmed
    ..Shigellae are noteworthy for their multiple drug resistance, having gradually acquired resistance to most widely use and inexpensive antimicrobial drugs...
  46. Bergmann R, Sagar V, Nitsche Schmitz D, Chhatwal G. first detection of trimethoprim resistance determinant dfrG in Streptococcus pyogenes clinical isolates in India. Antimicrob Agents Chemother. 2012;56:5424-5 pubmed publisher
  47. Sivapalasingam S, Nelson J, Joyce K, Hoekstra M, Angulo F, Mintz E. High prevalence of antimicrobial resistance among Shigella isolates in the United States tested by the National Antimicrobial Resistance Monitoring System from 1999 to 2002. Antimicrob Agents Chemother. 2006;50:49-54 pubmed
    ..All isolates were susceptible to ceftriaxone. Since 1986, resistance to ampicillin and TMP-SMX has dramatically increased. Shigella isolates in the United States remain susceptible to ciprofloxacin and ceftriaxone. ..
  48. Huovinen P. Resistance to trimethoprim-sulfamethoxazole. Clin Infect Dis. 2001;32:1608-14 pubmed
    ..Today, detailed and reliable knowledge on the resistance of bacterial pathogens to both TMP-SMZ and TMP is an essential requirement for the safe and effective use of these drugs in all clinical settings. ..
  49. Yue L, Chen X, Li S, Liao X, Zhuang N, Zhang Y, et al. First report of plasmid-mediated quinolone resistance qnrA1 gene in Klebsiella pneumoniae isolate of animal origin. Foodborne Pathog Dis. 2011;8:565-8 pubmed publisher
    ..The presence of qnrA1 in health animal commensal bacteria should be worthy of note. This is the first report of qnrA1 in K. pneumoniae and dfrA27 in an Enterobacteriaceae isolate of animal origin...
  50. Sahm D, Benninger M, Evangelista A, Yee Y, Thornsberry C, Brown N. Antimicrobial resistance trends among sinus isolates of Streptococcus pneumoniae in the United States (2001-2005). Otolaryngol Head Neck Surg. 2007;136:385-9 pubmed
    ..pneumoniae isolates appear to have stabilized over the past 5 years. Resistance rates remain elevated for penicillin and macrolides, whereas the high prevalence of multidrug resistance remains a concern. ..
  51. Tait S, Amyes S. Trimethoprim resistant dihydrofolate reductases in normal faecal flora isolated in India. Epidemiol Infect. 1994;113:247-58 pubmed
    ..The dhfrV, first characterized in Sri Lanka, would seem to have a local distribution in this region of Asia but is distinguishable from the dhfrIb only by the use of an oligo-probe. ..
  52. Toleman M, Bennett P, Bennett D, Jones R, Walsh T. Global emergence of trimethoprim/sulfamethoxazole resistance in Stenotrophomonas maltophilia mediated by acquisition of sul genes. Emerg Infect Dis. 2007;13:559-65 pubmed
    ..maltophilia and are geographically widespread, findings that reinforce the need for ongoing resistance surveillance. ..
  53. Alonso H, Gready J. Integron-sequestered dihydrofolate reductase: a recently redeployed enzyme. Trends Microbiol. 2006;14:236-42 pubmed
    ..This information supports the ideas that DfrB DHFR is a poorly adapted catalyst and has recently been recruited to perform a novel enzymatic activity in response to selective pressure. ..